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Wang D, Yan D, Yan M, Tian H, Jiang H, Zhu B, Chen Y, Peng T, Wan Y. The efficacy of hypothermia combined with thrombolysis or mechanical thrombectomy on acute ischemic stroke: a systematic review and meta-analysis. Front Neurol 2025; 15:1481115. [PMID: 39839874 PMCID: PMC11746097 DOI: 10.3389/fneur.2024.1481115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 12/18/2024] [Indexed: 01/23/2025] Open
Abstract
Background Therapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. In recent years, the safety and efficacy of hypothermia combining thrombolysis or mechanical thrombectomy have attracted widespread attention. The primary objective of the study was to evaluate the effectiveness and safety of hypothermia by combining reperfusion therapy in acute ischemic stroke patients. Methods A systematic search was performed in PubMed, EMBASE, Cochrane Library, and the Clinical Trial Registries on articles published until May 2024. The full-text articles were thoroughly reviewed, and relevant information regarding study characteristics and outcomes was extracted. Mantel-Haenszel (M-H) random-effects model was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). In addition, subgroup analyses were performed focusing on the different hypothermia modalities and duration. Results After screening 2,265 articles, 10 studies were included in the present analysis with a total sample size of 785. Forest plots of clinical outcomes were as follows: modified Rankin Scale (mRS) ≤2 at 3 months (RR = 1.28, 95% CI 1.01-1.61, p = 0.04), mortality within 3 months (RR = 0.95, 95% CI 0.69-1.29, p = 0.73), total complications (RR = 1.02, 95% CI 0.89-1.16, p = 0.77) and pneumonia (RR = 1.35, 95% CI 0.76-2.40, p = 0.31). Subgroup analyses indicated a mild protective effect of selective cerebral hypothermia; however, the difference in mortality between the hypothermia and control groups was not statistically significant (RR = 0.88, 95% CI 0.57-1.35, p = 0.55). Patients undergoing hypothermia for 24-48 h experienced a higher rate of overall complications (RR = 1.37, 95% CI 1.01-1.86, p = 0.04) and pneumonia (RR = 2.84, 95% CI 1.05-7.66, p = 0.04). Conclusion The preliminary evidence supports the safety and feasibility of hypothermia combined with reperfusion therapy, which should be further investigated in randomized controlled studies. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024556625.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Yue Wan
- Department of Neurology, Hubei No. 3 People’s Hospital of Jianghan University, Wuhan, China
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Zhu FY, Chen YM, Ma SM, Shao Q. The value of quantitative dual-energy CT parameters in predicting delayed haemorrhage after thrombectomy in acute ischaemic stroke. J Stroke Cerebrovasc Dis 2024; 33:108083. [PMID: 39393510 DOI: 10.1016/j.jstrokecerebrovasdis.2024.108083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 08/26/2024] [Accepted: 10/08/2024] [Indexed: 10/13/2024] Open
Abstract
OBJECTIVE This study investigates the predictive value of dual-energy CT Rho/Z quantitative parameters for delayed hemorrhage post-thrombectomy in patients with acute ischemic stroke MATERIALS AND METHODS: A retrospective analysis was conducted on 80 patients who underwent dual-energy CT after thrombectomy for acute ischemic stroke. Patients were divided into delayed hemorrhage/no delayed hemorrhage, symptomatic intracranial hemorrhage/asymptomatic intracranial hemorrhage and cerebral parenchymal hematoma/no cerebral parenchymal hematoma groups RESULTS: The quantitative parameters significantly associated with delayed hemorrhage are DEI and Zeff (p < 0.001), with the optimal cutoff values for DEI and Zeff being 0.045 and 9.355, respectively. The quantitative parameters significantly associated with symptomatic intracranial hemorrhage are DEI and Zeff (p < 0.001), with the optimal cutoff values being 0.064 and 9.422, respectively. The parameters significantly associated with cerebral parenchymal hematoma are DEI and Zeff (p < 0.001), with the optimal cutoff values for DEI and Zeff being 0.058 and 9.09, respectively CONCLUSION: The DEI and Zeff parameters derived from dual-energy CT Rho/Z analysis are valuable in predicting delayed hemorrhage, symptomatic intracranial hemorrhage, and cerebral parenchymal hematoma in patients with acute ischemic stroke following thrombectomy.
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Affiliation(s)
- Feng-Ying Zhu
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding 071000, China
| | - Ying-Min Chen
- Department of Radiology, Hebei General Hospital, Shijiazhuang 050057, China.
| | - Shu-Min Ma
- Department of Radiology, HanDan General Hospital, Handan 057150, China
| | - Qiu Shao
- Department of Radiology, Hebei General Hospital, Shijiazhuang 050057, China
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Jiang X, Chen L, Wang J, Fang J, Ma M, Zhou M, Zheng H, Hu F, Zhou D, He L. Combined Selective Endovascular Brain Hypothermia with Edaravone Dexborneol versus Edaravone Dexborneol Alone for Endovascular Treatment in Acute Ischemic Stroke (SHE): Protocol for a Multicenter, Single-Blind, Randomized Controlled Study. Cerebrovasc Dis 2024:1-7. [PMID: 39427648 DOI: 10.1159/000542011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 10/09/2024] [Indexed: 10/22/2024] Open
Abstract
INTRODUCTION Selective endovascular brain hypothermia has been proposed as a potential neuroprotective strategy; however, its effectiveness is still not well established. The primary objective of this trial is to investigate the efficacy and safety of selective endovascular brain hypothermia with edaravone dexborneol for endovascular treatment in acute ischemic stroke (AIS). METHODS The SHE study is a multicenter, single-blind, randomized controlled clinical trial. Patients with acute anterior circulation ischemic stroke who received endovascular treatment within 24 h after stroke onset and achieved successful recanalization will be enrolled and centrally randomized into combined selective endovascular brain hypothermia with edaravone dexborneol or edaravone dexborneol alone groups in a 1:1 ratio (n = 564). Patients allocated to the hypothermia group will receive 300 mL cool saline at 4°C through guiding catheter (30 mL/min) into target vessel within 3 min after recanalization and then receive edaravone dexborneol (edaravone dexborneol 15 mL + NS 100 mL ivgtt bid for 10-14 days) within 24 h after admission. The control group will receive 300 mL 37°C saline (30 mL/min) infused into target vessel through guiding catheter and then receive edaravone dexborneol. All patients enrolled will receive standard care according to current guidelines for stroke management. The primary outcome is the proportion of functional independence, defined as a mRS score of 0-2 at 90 days after randomization. CONCLUSION This is a randomized clinical trial with a large sample size to compare combined selective endovascular brain hypothermia and edaravone dexborneol with edaravone dexborneol alone in patients with acute anterior ischemic stroke. The SHE trial aims to provide further evidence of the benefit of selective endovascular brain hypothermia in AIS patients who received endovascular treatment.
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Affiliation(s)
- Xin Jiang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Lizhang Chen
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Jian Wang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Jinghuan Fang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Mengmeng Ma
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Muke Zhou
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Hongbo Zheng
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Fayun Hu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Dong Zhou
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Li He
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
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Wang A, Meng X, Chen Q, Chu Y, Zhou Q, Jiang D, Wang Z. Efficacy analysis of mechanical thrombectomy combined with prolonged mild hypothermia in the treatment of acute middle cerebral artery occlusion: a single-center retrospective cohort study. Front Neurol 2024; 15:1406293. [PMID: 39045428 PMCID: PMC11263112 DOI: 10.3389/fneur.2024.1406293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 06/20/2024] [Indexed: 07/25/2024] Open
Abstract
Objective To determine the efficacy of mechanical thrombectomy combined with prolonged mild hypothermia compared with conventional treatment in managing acute middle cerebral artery occlusion, and to explore whether extending the duration of hypothermia can improve neurological function. Method From 2018 to June 2023, a retrospective analysis was conducted on 45 patients with acute middle cerebral artery occlusion treated at the NICU of Suzhou Kowloon Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. After thrombectomy, patients were admitted to the neurological intensive care unit (NICU) for targeted temperature management. Patients were divided into two groups: the mild hypothermia group (34.5-35.9°C) receiving 5-7 days of treatment, and the normothermia group (control group) whose body temperature was kept between 36 and 37.5°C using pharmacological and physical cooling methods. Baseline characteristics and temperature changes were compared between the two groups of patients. The primary outcome was the modified Rankin Scale (mRS) score at 3 month after surgery, and the secondary outcomes were related complications and mortality rate. Prognostic risk factors were investigated using both univariate and multivariate logistic regression analyses. Results Among 45 patients, 21 underwent prolonged mild hypothermia, and 24 received normothermia, with no significant differences in baseline characteristics between the two groups. The duration of mild hypothermia ranged from 5 to 7 days. The incidence of chills (33.3% vs. 8.3%, p = 0.031) and constipation (57.1% vs. 20.8%, p = 0.028) was significantly higher in the mild hypothermia group compared with the control group. There was no significant difference in mortality rates between the mild hypothermia and the control group (4.76% vs. 8.33%, p = 1.000, OR = 1.75, 95% CI, 0.171-17.949). At 3 month, there was no significant difference in the modified mRS (0-3) score between the mild hypothermia and control groups (52.4% vs. 25%, p = 0.114, OR = 0.477, 95% CI, 0.214-1.066). Infarct core volume was an independent risk factor for adverse neurological outcomes. Conclusion Prolonged mild hypothermia following mechanical thrombectomy had no severe complications and shows a trend to improve the prognosis of neurological function. The Infarct core volume on CTP was an independent risk factor for predicting neurological function.
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Affiliation(s)
- Anqi Wang
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China
| | - Xuan Meng
- Department of Neurosurgery, Suzhou BOE Hospital, Suzhou, China
| | - Qin Chen
- Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China
| | - YanFei Chu
- Department of Neurosurgery, Suzhou BOE Hospital, Suzhou, China
| | - Qiang Zhou
- Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China
| | - DongYi Jiang
- Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China
| | - Zhimin Wang
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Bai X, Qu X, Nogueira RG, Chen W, Zhao H, Cao W, Gao P, Yang B, Wang Y, Chen J, Chen Y, Wang Y, Shang F, Cheng W, Xu Y, Qi M, Jiang L, Chen W, Lu J, Ma Q, Wang N, Jiao L. Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study. Int J Surg 2024; 110:2065-2070. [PMID: 38668659 PMCID: PMC11020036 DOI: 10.1097/js9.0000000000001127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 01/09/2024] [Indexed: 04/29/2024]
Abstract
BACKGROUND Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.
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Affiliation(s)
- Xuesong Bai
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Xin Qu
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Raul G. Nogueira
- University of Pittsburgh Medical Center Stroke Institute, Department of Neurology and Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, USA
| | - Wenhuo Chen
- Department of Neurology, Zhangzhou Affiliated Hospital, Fujian Medical University, Zhangzhou City, Fujian Province, People’s Republic of China
| | - Hao Zhao
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Wenbo Cao
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Peng Gao
- Department of Neurosurgery
- Department of Interventional Neuroradiology
- Department of Neurosurgery, China International Neuroscience Institute
| | - Bin Yang
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Yabing Wang
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Jian Chen
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Yanfei Chen
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | | | - Feng Shang
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Weitao Cheng
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Yueqiao Xu
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Meng Qi
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Lidan Jiang
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Wenjin Chen
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Jie Lu
- Department of Radiology and Nuclear Medicine
- Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing
| | - Qingfeng Ma
- Department of Neurology, Xuanwu Hospital, Capital Medical University
| | - Ning Wang
- Department of Neurosurgery
- Department of Neurosurgery, China International Neuroscience Institute
| | - Liqun Jiao
- Department of Neurosurgery
- Department of Interventional Neuroradiology
- Department of Neurosurgery, China International Neuroscience Institute
- Department of Neurosurgery and Neurology, Jinan Hospital of Xuanwu Hospital, Shandong First Medical University, Jinan
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Díaz-Peregrino R, Kentar M, Trenado C, Sánchez-Porras R, Albiña-Palmarola P, Ramírez-Cuapio FL, San-Juan D, Unterberg A, Woitzik J, Santos E. The neurophysiological effect of mild hypothermia in gyrencephalic brains submitted to ischemic stroke and spreading depolarizations. Front Neurosci 2024; 18:1302767. [PMID: 38567280 PMCID: PMC10986791 DOI: 10.3389/fnins.2024.1302767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 02/22/2024] [Indexed: 04/04/2024] Open
Abstract
Objective Characterize the neurophysiological effects of mild hypothermia on stroke and spreading depolarizations (SDs) in gyrencephalic brains. Methods Left middle cerebral arteries (MCAs) of six hypothermic and six normothermic pigs were permanently occluded (MCAo). Hypothermia began 1 h after MCAo and continued throughout the experiment. ECoG signals from both frontoparietal cortices were recorded. Five-minute ECoG epochs were collected 5 min before, at 5 min, 4, 8, 12, and 16 h after MCAo, and before, during, and after SDs. Power spectra were decomposed into fast (alpha, beta, and gamma) and slow (delta and theta) frequency bands. Results In the vascular insulted hemisphere under normothermia, electrodes near the ischemic core exhibited power decay across all frequency bands at 5 min and the 4th hour after MCAo. The same pattern was registered in the two furthest electrodes at the 12th and 16th hour. When mild hypothermia was applied in the vascular insulted hemispheres, the power decay was generalized and seen even in electrodes with uncompromised blood flow. During SD analysis, hypothermia maintained increased delta and beta power during the three phases of SDs in the furthest electrode from the ischemic core, followed by the second furthest and third electrode in the beta band during preSD and postSD segments. However, in hypothermic conditions, the third electrode showed lower delta, theta, and alpha power. Conclusion Mild hypothermia attenuates all frequency bands in the vascularly compromised hemisphere, irrespective of the cortical location. During SD formation, it preserves power spectra more significantly in electrodes further from the ischemic core.
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Affiliation(s)
- Roberto Díaz-Peregrino
- Department of Neurosurgery, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
| | - Modar Kentar
- Department of Neurosurgery, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
- Departement of Neurosurgery, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
| | - Carlos Trenado
- Heinrich Heine University, Medical Faculty, Institute of Clinical Neuroscience and Medical Psychology, Düsseldorf, Germany
- Institute for the Future of Education Europe, Tecnológico de Monterrey, Cantabria, Spain
| | - Renán Sánchez-Porras
- Department of Neurosurgery, Evangelisches Krankenhaus, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Pablo Albiña-Palmarola
- Neuroradiologische Klinik, Klinikum Stuttgart, Stuttgart, Germany
- Medizinische Fakultät, Universität Duisburg-Essen, Essen, Germany
- Department of Anatomy, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco L. Ramírez-Cuapio
- Department of Neurosurgery, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
| | - Daniel San-Juan
- Epilepsy Clinic, National Institute of Neurology and Neurosurgery, Manuel Velasco Suárez, Mexico City, Mexico
| | - Andreas Unterberg
- Department of Neurosurgery, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
| | - Johannes Woitzik
- Department of Neurosurgery, Evangelisches Krankenhaus, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Edgar Santos
- Department of Neurosurgery, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
- Department of Neurosurgery, Evangelisches Krankenhaus, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
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Binda DD, Baker MB, Varghese S, Wang J, Badenes R, Bilotta F, Nozari A. Targeted Temperature Management for Patients with Acute Ischemic Stroke: A Literature Review. J Clin Med 2024; 13:586. [PMID: 38276093 PMCID: PMC10816923 DOI: 10.3390/jcm13020586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 01/03/2024] [Accepted: 01/11/2024] [Indexed: 01/27/2024] Open
Abstract
Despite significant advances in medical imaging, thrombolytic therapy, and mechanical thrombectomy, acute ischemic strokes (AIS) remain a major cause of mortality and morbidity globally. Targeted temperature management (TTM) has emerged as a potential therapeutic intervention, aiming to mitigate neuronal damage and improve outcomes. This literature review examines the efficacy and challenges of TTM in the context of an AIS. A comprehensive literature search was conducted using databases such as PubMed, Cochrane, Web of Science, and Google Scholar. Studies were selected based on relevance and quality. We identified key factors influencing the effectiveness of TTM such as its timing, depth and duration, and method of application. The review also highlighted challenges associated with TTM, including increased pneumonia rates. The target temperature range was typically between 32 and 36 °C, with the duration of cooling from 24 to 72 h. Early initiation of TTM was associated with better outcomes, with optimal results observed when TTM was started within the first 6 h post-stroke. Emerging evidence indicates that TTM shows considerable potential as an adjunctive treatment for AIS when implemented promptly and with precision, thereby potentially mitigating neuronal damage and enhancing overall patient outcomes. However, its application is complex and requires the careful consideration of various factors.
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Affiliation(s)
- Dhanesh D. Binda
- Department of Anesthesiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; (D.D.B.); (M.B.B.); (S.V.); (J.W.); (A.N.)
| | - Maxwell B. Baker
- Department of Anesthesiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; (D.D.B.); (M.B.B.); (S.V.); (J.W.); (A.N.)
| | - Shama Varghese
- Department of Anesthesiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; (D.D.B.); (M.B.B.); (S.V.); (J.W.); (A.N.)
| | - Jennifer Wang
- Department of Anesthesiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; (D.D.B.); (M.B.B.); (S.V.); (J.W.); (A.N.)
| | - Rafael Badenes
- Department Anesthesiology, Surgical-Trauma Intensive Care and Pain Clinic, Hospital Clínic Universitari, University of Valencia, 46010 Valencia, Spain
| | - Federico Bilotta
- Department of Anaesthesiology, Critical Care and Pain Medicine, Policlinico Umberto I Teaching Hospital, Sapienza University of Rome, 00185 Rome, Italy;
| | - Ala Nozari
- Department of Anesthesiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; (D.D.B.); (M.B.B.); (S.V.); (J.W.); (A.N.)
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Gao Y, Li M, Jiang M, Zhang Y, Ji X. A narrative review of intravascular catheters in therapeutic hypothermia. Brain Circ 2024; 10:11-20. [PMID: 38655445 PMCID: PMC11034446 DOI: 10.4103/bc.bc_32_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/22/2023] [Accepted: 07/27/2023] [Indexed: 04/26/2024] Open
Abstract
Therapeutic hypothermia (TH) has been regarded as a promising neuroprotective method for acute ischemic stroke (AIS) for decades. During the development of TH, most researchers focused on improving hypothermic benefits by optimizing treatment processes and conditions. Intravenous thrombolysis and endovascular thrombectomy, for instance, have been introduced into AIS treatment. However, the lack of specialized intervention consumables, especially intervention catheter, led to inaccurate and uncontrolled hypothermic temperature, limited the efficacy of TH. In this review, intervention catheters as well as accessory equipment utilized in TH treatment has been summarized. Hopefully, this review may inspire the future development of TH specialized intervention catheter, enhance the outcome of TH, and neuroprotective efficacy in AIS.
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Affiliation(s)
- Yuan Gao
- School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, China
- Research Institute for Frontier Science, Beihang University, Beijing, China
| | - Ming Li
- Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Miaowen Jiang
- School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, China
- Research Institute for Frontier Science, Beihang University, Beijing, China
| | - Yang Zhang
- Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xunming Ji
- School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, China
- Research Institute for Frontier Science, Beihang University, Beijing, China
- Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
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Xu R, Nair SK, Kilgore CB, Xie ME, Jackson CM, Hui F, Gailloud P, McDougall CG, Gonzalez LF, Huang J, Tamargo RJ, Caplan J. Hypothermia is Associated with Improved Neurological Outcomes After Mechanical Thrombectomy. World Neurosurg 2024; 181:e126-e132. [PMID: 37690581 PMCID: PMC11060169 DOI: 10.1016/j.wneu.2023.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 09/03/2023] [Accepted: 09/04/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND Acute ischemic stroke (AIS) is the second leading cause of death globally. Mechanical thrombectomy (MT) has improved patient prognosis but expedient treatment is still necessary to minimize anoxic injury. Lower intraoperative body temperature decreases cerebral oxygen demand, but the role of hypothermia in treatment of AIS with MT is unclear. METHODS We retrospectively reviewed patients undergoing MT for AIS from 2014 to 2020 at our institution. Patient demographics, comorbidities, intraoperative parameters, and outcomes were collected. Maximum body temperature was extracted from minute-by-minute anesthesia readings, and patients with maximal temperature below 36°C were considered hypothermic. Risk factors were assessed by χ2 and multivariate ordinal regression. RESULTS Of 68 patients, 27 (40%) were hypothermic. There was no significant association of hypothermia with patient age, comorbidities, time since last known well, number of passes intraoperatively, favorable revascularization, tissue plasminogen activator use, and immediate postoperative complications. Hypothermic patients exhibited better neurologic outcome at 3-month follow-up (P = 0.02). On multivariate ordinal regression, lower maximum intraoperative body temperature was associated with improved 3-month outcomes (P < 0.001), when adjusting for other factors influencing neurological outcomes. Other significant protective factors included younger age (P = 0.03), better revascularization (P = 0.03), and conscious sedation (P = 0.02). CONCLUSIONS Lower intraoperative body temperature during MT was independently associated with improved neurological outcome in this single center retrospective series. These results may help guide clinicians in employing therapeutic hypothermia during MT to improve long-term neurologic outcomes from AIS, although larger studies are needed.
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Affiliation(s)
- Risheng Xu
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sumil K Nair
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Collin B Kilgore
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Michael E Xie
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Christopher M Jackson
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ferdinand Hui
- Division of Neurointerventional Surgery, Queen's Medical Center, Honolulu, Hawaii, USA
| | - Phillipe Gailloud
- Department of Interventional Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - L Fernando Gonzalez
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Judy Huang
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Rafael J Tamargo
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Justin Caplan
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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10
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Chen J, Xu S, Lee H, Wu L, He X, Zhao W, Zhang M, Ma Y, Ding Y, Fu Y, Wu C, Li M, Jiang M, Cheng H, Li S, Ma T, Ji X, Wu D. Hypothermic neuroprotection by targeted cold autologous blood transfusion in a non-human primate stroke model. Sci Bull (Beijing) 2023:S2095-9273(23)00392-4. [PMID: 37391345 DOI: 10.1016/j.scib.2023.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/06/2023] [Accepted: 06/12/2023] [Indexed: 07/02/2023]
Abstract
Over decades, nearly all attempts to translate the benefits of therapeutic hypothermia in stroke models of lower-order species to stroke patients have failed. Potentially overlooked reasons may be biological gaps between different species and the mismatched initiation of therapeutic hypothermia in translational studies. Here, we introduce a novel strategy of selective therapeutic hypothermia in a non-human primate ischemia-reperfusion model, in which autologous blood was cooled ex vivo and the cool blood transfusion was administered at the middle cerebral artery just after the onset of reperfusion. Cold autologous blood cooled the targeted brain rapidly to below 34 °C while the rectal temperature remained around 36 °C with the assistance of a heat blanket during a 2-h hypothermic process. Therapeutic hypothermia or extracorporeal-circulation related complications were not observed. Cold autologous blood treatment reduced infarct sizes, preserved white matter integrity, and improved functional outcomes. Together, our results suggest that therapeutic hypothermia, induced by cold autologous blood transfusion, was achieved in a feasible, swift, and safe way in a non-human primate model of stroke. More importantly, this novel hypothermic approach conferred neuroprotection in a clinically relevant model of ischemic stroke due to reduced brain damage and improved neurofunction. This study reveals an underappreciated potential for this novel hypothermic modality for acute ischemic stroke in the era of effective reperfusion.
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Affiliation(s)
- Jian Chen
- Department of Neurosurgery, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Shuaili Xu
- China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Hangil Lee
- Department of Neurological Surgery, Wayne State University School of Medicine, Detroit MI 46801, USA
| | - Longfei Wu
- Department of Neurology, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Xiaoduo He
- China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Wenbo Zhao
- Department of Neurology, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Mo Zhang
- Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Yanhui Ma
- Department of Anesthesiology, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Yuchuan Ding
- Department of Neurological Surgery, Wayne State University School of Medicine, Detroit MI 46801, USA
| | - Yongjuan Fu
- Department of Pathology, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Chuanjie Wu
- Department of Neurology, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China
| | - Ming Li
- Department of Neurosurgery, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China
| | - Miuwen Jiang
- Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China
| | - Huakun Cheng
- Department of Neurosurgery, Heilongjiang Provincial Hospital, Harbin 1500036, China
| | - Shengli Li
- Department of Laboratory Animal Science, Capital Medical University, Beijing 100069, China
| | - Ting Ma
- Department of Anesthesiology, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China.
| | - Xunming Ji
- Department of Neurosurgery, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
| | - Di Wu
- China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China.
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11
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Huang J, Wang P, Wen H. The safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke: A systematic meta-analysis. Clinics (Sao Paulo) 2023; 78:100218. [PMID: 37269787 DOI: 10.1016/j.clinsp.2023.100218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/26/2023] [Accepted: 04/24/2023] [Indexed: 06/05/2023] Open
Abstract
BACKGROUND Stroke is a major global public health problem, affecting 13.7 million people worldwide. Previous studies have found a neuroprotective effect of hypothermia therapy and the efficacy and safety of combined hypothermia and mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke have also attracted attention. OBJECTIVE In the present research, the authors conducted a meta-analysis to comprehensively assess the safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke. METHODS Articles published from January 2001 to May 2022 were searched from Google Scholar, Baidu Scholar and PubMed to evaluate the clinical significance of hypothermia treatment in ischemic stroke. Complications, short-term mortality, and the modified Rankin Scale (mRS) in the full text was extracted. RESULTS 89 publications were selected and 9 among them were included in this study with sample size of 643. All selected studies are in accordance with the inclusion criteria. Forest plot of clinical characteristics was as follows: complications (RR = 1.132, 95% CI 0.942‒1.361, p = 0.186, I2 = 37.2%), mortality within 3 months (RR = 1.076, 95% CI 0.694‒1.669, p = 0.744, I2 = 0.00%), mRS ≤ 1 at 3 months (RR = 1.138, 95% CI 0.829‒1.563, p = 0.423, I2 = 26.0%), mRS ≤ 2 at 3 months (RR = 1.672, 95% CI 1.236‒2.263, p = 0.001, I2=49.6%) and mRS ≤ 3 at 3 months (RR = 1.518, 95% CI 1.128‒2.043, p = 0.006, I2 = 0.00%). The funnel plot suggested that there was no significant publication bias in the meta-analysis on complications, mortality within 3 months, mRS ≤ 1 at 3 months and mRS ≤ 2 at 3 months. CONCLUSION In summary, the results showed that hypothermia treatment was correlated with mRS ≤ 2 at 3 months, but not linked with complications and mortality within 3 months.
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Affiliation(s)
- Jiankang Huang
- Department of Neurology, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, Jiangshu 211200, China
| | - Peng Wang
- Department of Neurology, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, Jiangshu 211200, China
| | - Hongbo Wen
- Department of Neurology, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, Jiangshu 211200, China.
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12
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Kentar M, Ramirez-Cuapio FL, Gutiérrez-Herrera MA, Sanchez-Porras R, Díaz-Peregrino R, Holzwarth N, Maier-Hein L, Woitzik J, Santos E. Mild hypothermia reduces spreading depolarizations and infarct size in a swine model. J Cereb Blood Flow Metab 2023; 43:999-1009. [PMID: 36722153 PMCID: PMC10196741 DOI: 10.1177/0271678x231154604] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 12/06/2022] [Accepted: 12/15/2022] [Indexed: 02/02/2023]
Abstract
Spreading depolarizations (SDs) have been linked to infarct volume expansion following ischemic stroke. Therapeutic hypothermia provides a neuroprotective effect after ischemic stroke. This study aimed to evaluate the effect of hypothermia on the propagation of SDs and infarct volume in an ischemic swine model. Through left orbital exenteration, middle cerebral arteries were surgically occluded (MCAo) in 16 swine. Extensive craniotomy and durotomy were performed. Six hypothermic and five normothermic animals were included in the analysis. An intracranial temperature probe was placed right frontal subdural. One hour after ischemic onset, mild hypothermia was induced and eighteen hours of electrocorticographic (ECoG) and intrinsic optical signal (IOS) recordings were acquired. Postmortem, 4 mm-thick slices were stained with 2,3,5-triphenyltetrazolium chloride to estimate the infarct volume. Compared to normothermia (36.4 ± 0.4°C), hypothermia (32.3 ± 0.2°C) significantly reduced the frequency and expansion of SDs (ECoG: 3.5 ± 2.1, 73.2 ± 5.2% vs. 1.0 ± 0.7, 41.9 ± 21.8%; IOS 3.9 ± 0.4, 87.6 ± 12.0% vs. 1.4 ± 0.7, 67.7 ± 8.3%, respectively). Further, infarct volume among hypothermic animals (23.2 ± 1.8% vs. 32.4 ± 2.5%) was significantly reduced. Therapeutic hypothermia reduces infarct volume and the frequency and expansion of SDs following cerebral ischemia.
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Affiliation(s)
- Modar Kentar
- Department of Neurosurgery,
University of Heidelberg, Heidelberg, Germany
| | | | | | - Renan Sanchez-Porras
- Department of Neurosurgery,
Evangelisches Krankenhaus Oldenburg, Carl von Ossietzky University of Oldenburg,
Oldenburg, Germany
| | | | - Niklas Holzwarth
- Division of Intelligent Medical
Systems, German Cancer Research Center, Heidelberg, Germany
| | - Lena Maier-Hein
- Division of Intelligent Medical
Systems, German Cancer Research Center, Heidelberg, Germany
| | - Johannes Woitzik
- Department of Neurosurgery,
Evangelisches Krankenhaus Oldenburg, Carl von Ossietzky University of Oldenburg,
Oldenburg, Germany
| | - Edgar Santos
- Department of Neurosurgery,
University of Heidelberg, Heidelberg, Germany
- Department of Neurosurgery,
Evangelisches Krankenhaus Oldenburg, Carl von Ossietzky University of Oldenburg,
Oldenburg, Germany
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13
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Wan Y, Tian H, Wang H, Wang D, Jiang H, Fang Q. Selective intraarterial hypothermia combined with mechanical thrombectomy for acute cerebral infarction based on microcatheter technology: A single-center, randomized, single-blind controlled study. Front Neurol 2023; 14:1039816. [PMID: 36873429 PMCID: PMC9978520 DOI: 10.3389/fneur.2023.1039816] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 01/27/2023] [Indexed: 02/18/2023] Open
Abstract
Objective To investigate the safety and efficacy of selective intraarterial hypothermia combined with mechanical thrombectomy in the treatment of acute cerebral infarction based on microcatheter technology. Methods A total of 142 patients with anterior circulation large vessel occlusion were randomly assigned to the hypothermic treatment group (test group) and the conventional treatment group (control group). National Institutes of Health Stroke Scale (NIHSS) scores, postoperative infarct volume, the 90-day good prognosis rate (modified Rankin Scale (mRS) score ≤ 2 points), and the mortality rate of the two groups were compared and analyzed. Blood specimens were collected from patients before and after treatment. Serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6), IL-10, and RNA-binding motif protein 3 (RBM3) were measured. Results The 7-day postoperative cerebral infarct volume [(63.7 ± 22.1) ml vs. (88.5 ± 20.8) ml] and NIHSS scores at postoperative Days 1, 7, and 14 [(6.8 ± 3.8) points vs. (8.2 ± 3.5) points; (2.6 ± 1.6) points vs. (4.0 ± 1.8) points; (2.0 ± 1.2) points vs. (3.5 ± 2.1) points] in the test group were significantly lower than those in the control group. The good prognosis rate at 90 days postoperatively (54.9 vs. 35.2%, P = 0.018) was significantly higher in the test group than in the control group. The 90-day mortality rate was not statistically significant (7.0 vs. 8.5%, P = 0.754). Immediately after surgery and 1 day after surgery, SOD, IL-10, and RBM3 levels in the test group were relatively higher than those in the control group, and the differences were statistically significant. Immediately after surgery and 1 day after surgery, MDA and IL-6 levels in the test group were relatively reduced compared with those in the control group, and the differences were statistically significant (P < 0.05). In the test group, RBM3 was positively correlated with SOD and IL-10. Conclusion Mechanical thrombectomy combined with intraarterial cold saline perfusion is a safe and effective measure for the treatment of acute cerebral infarction. Postoperative NIHSS scores and infarct volumes were significantly improved with this strategy compared with simple mechanical thrombectomy, and the 90-day good prognosis rate was improved. The mechanism by which this treatment exerts its cerebral protective effect may be by inhibiting the transformation of the ischaemic penumbra of the infarct core area, scavenging some oxygen free radicals, reducing inflammatory injury to cells after acute infarction and ischaemia-reperfusion, and promoting RBM3 production in cells.
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Affiliation(s)
- Yue Wan
- Department of Neurology, The First Affiliated Hospital of Suzhou University, Suzhou, Liaoning, China
- Department of Neurology, Hubei Provincial Third People's Hospital, Zhongshan Hospital, Wuhan, Hubei, China
| | - Hao Tian
- Department of Neurology, Hubei Provincial Third People's Hospital, Zhongshan Hospital, Wuhan, Hubei, China
| | - Hui Wang
- Department of Neurology, The First Affiliated Hospital of Suzhou University, Suzhou, Liaoning, China
| | - DaPeng Wang
- Department of Neurology, The First Affiliated Hospital of Suzhou University, Suzhou, Liaoning, China
| | - HaiWei Jiang
- Department of Neurology, Hubei Provincial Third People's Hospital, Zhongshan Hospital, Wuhan, Hubei, China
| | - Qi Fang
- Department of Neurology, The First Affiliated Hospital of Suzhou University, Suzhou, Liaoning, China
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14
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Chen X, An H, Wu D, Ji X. Research progress of selective brain cooling methods in the prehospital care for stroke patients: A narrative review. Brain Circ 2023; 9:16-20. [PMID: 37151794 PMCID: PMC10158655 DOI: 10.4103/bc.bc_88_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/14/2023] [Accepted: 01/29/2023] [Indexed: 05/09/2023] Open
Abstract
Over the past four decades, therapeutic hypothermia (TH) has long been suggested as a promising neuroprotective treatment of acute ischemic stroke (AIS). Much attention has focus on keeping the hypothermic benefits and removing side effects of systemic hypothermia. In the past few years, the advent of intravenous thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of AIS treatment. With recent research emphasizing ways to plus neuroprotective treatments to reperfusion therapy, the spotlight is now shifting toward the study of how selective brain hypothermia can offset the drawbacks of systemic hypothermia and be applied in prehospital condition. This mini-review summarizes current brain cooling methods that can be used for inducing selective hypothermia in prehospital care. It will guide the future development of selective cooling methods, extend the application of TH in prehospital care, and provide insights into the prospects of selective hypothermia in AIS.
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Affiliation(s)
- Xi Chen
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China
| | - Hong An
- Department of Neurology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Di Wu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China
| | - Xunming Ji
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China
- Address for correspondence: Dr. Xunming Ji, Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China. E-mail:
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15
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Hong JM, Lee JS, Lee YB, Shin DH, Shin DI, Hwang YH, Ahn SH, Kim JG, Sohn SI, Kwon SU, Lee JS, Gwag BJ, Chamorro Á, Choi DW. Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial. Stroke 2022; 53:3250-3259. [PMID: 36065810 PMCID: PMC9586831 DOI: 10.1161/strokeaha.122.039649] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 07/01/2022] [Accepted: 07/19/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Nelonemdaz is a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, as proven in preclinical ischemia-reperfusion studies. We aimed to evaluate the safety and efficacy of nelonemdaz in patients with acute ischemic stroke receiving endovascular reperfusion therapy. METHODS This phase II randomized trial involved participants with large-artery occlusion in the anterior circulation at baseline who received endovascular reperfusion therapy <8 hours from symptom onset at 7 referral stroke centers in South Korea between October 29, 2016, and June 1, 2020. Two hundred thirteen patients were screened and 209 patients were randomly assigned at a 1:1:1 ratio using a computer-generated randomization system. Patients were divided into 3 groups based on the medication received-placebo, low-dose (2750 mg) nelonemdaz, and high-dose (5250 mg) nelonemdaz. The primary outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 12 weeks. RESULTS Two hundred eight patients were assigned to the placebo (n=70), low-dose (n=71), and high-dose (n=67) groups. The groups had similar baseline characteristics. The primary outcome was achieved in 183 patients, and it did not differ among the groups (33/61 [54.1%], 40/65 [61.5%], and 36/57 [63.2%] patients; P=0.5578). The common odds ratio (90% CI) indicating a favorable shift in the modified Rankin Scale scores at 12 weeks was 1.55 (0.92-2.60) between the placebo and low-dose groups and 1.61 (0.94-2.76) between the placebo and high-dose groups. No serious adverse events were reported. CONCLUSIONS The study arms showed no significant difference in the proportion of patients achieving modified Rankin Scale scores of 0-2 at 12 weeks. Nevertheless, nelonemdaz-treated patients showed a favorable tendency toward achieving these scores at 12 weeks, without serious adverse effects. Thus, a large-scale phase III trial is warranted. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT02831088.
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Affiliation(s)
- Ji Man Hong
- Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Republic of Korea (J.M.H., Jin Soo Lee)
| | - Jin Soo Lee
- Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Republic of Korea (J.M.H., Jin Soo Lee)
| | - Yeong-Bae Lee
- Department of Neurology, Gachon University Gil Medical Center, Incheon, Republic of Korea (Y.-B.L., D.H.S.)
| | - Dong Hoon Shin
- Department of Neurology, Gachon University Gil Medical Center, Incheon, Republic of Korea (Y.-B.L., D.H.S.)
| | - Dong-Ick Shin
- Department of Neurology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea (D.-I.S.)
| | - Yang-Ha Hwang
- Department of Neurology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea (Y.-H.H.)
| | - Seong Hwan Ahn
- Department of Neurology, College of Medicine, Chosun University, Gwangju, Republic of Korea (S.H.A.)
| | - Jae Guk Kim
- Department of Neurology, Daejeon Eulji Medical Center, Eulji University, Daejeon, Republic of Korea (J.G.K.)
| | - Sung-Il Sohn
- Department of Neurology, Dongsan Medical Center, Keimyung University, Daegu, Republic of Korea (S.-I.S.)
| | - Sun U. Kwon
- Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ji Sung Lee
- Clinical Research Center (Ji Sung Lee), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byoung Joo Gwag
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea (B.J.G.)
| | - Ángel Chamorro
- Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona and August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain (A.C.)
| | - Dennis W. Choi
- Department of Neurology, Stony Brook University, NY (D.W.C.)
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16
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The utility of therapeutic hypothermia on cerebral autoregulation. JOURNAL OF INTENSIVE MEDICINE 2022; 3:27-37. [PMID: 36789361 PMCID: PMC9924009 DOI: 10.1016/j.jointm.2022.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 07/26/2022] [Accepted: 08/10/2022] [Indexed: 11/07/2022]
Abstract
Cerebral autoregulation (CA) dysfunction is a strong predictor of clinical outcome in patients with acute brain injury (ABI). CA dysfunction is a potential pathologic defect that may lead to secondary injury and worse functional outcomes. Early therapeutic hypothermia (TH) in patients with ABI is controversial. Many factors, including patient selection, timing, treatment depth, duration, and rewarming strategy, impact its clinical efficacy. Therefore, optimizing the benefit of TH is an important issue. This paper reviews the state of current research on the impact of TH on CA function, which may provide the basis and direction for CA-oriented target temperature management.
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17
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You JS, Kim JY, Yenari MA. Therapeutic hypothermia for stroke: Unique challenges at the bedside. Front Neurol 2022; 13:951586. [PMID: 36262833 PMCID: PMC9575992 DOI: 10.3389/fneur.2022.951586] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 09/08/2022] [Indexed: 12/24/2022] Open
Abstract
Therapeutic hypothermia has shown promise as a means to improving neurological outcomes at several neurological conditions. At the clinical level, it has been shown to improve outcomes in comatose survivors of cardiac arrest and in neonatal hypoxic ischemic encephalopathy, but has yet to be convincingly demonstrated in stroke. While numerous preclinical studies have shown benefit in stroke models, translating this to the clinical level has proven challenging. Major obstacles include cooling patients with typical stroke who are awake and breathing spontaneously but often have significant comorbidities. Solutions around these problems include selective brain cooling and cooling to lesser depths or avoiding hyperthermia. This review will cover the mechanisms of protection by therapeutic hypothermia, as well as recent progress made in selective brain cooling and the neuroprotective effects of only slightly lowering brain temperature. Therapeutic hypothermia for stroke has been shown to be feasible, but has yet to be definitively proven effective. There is clearly much work to be undertaken in this area.
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Affiliation(s)
- Je Sung You
- Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jong Youl Kim
- Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea
| | - Midori A. Yenari
- Department of Neurology, The San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, United States
- *Correspondence: Midori A. Yenari
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18
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Won SY, Kim MK, Song J, Lim YC. Therapeutic hypothermia in patients with poor-grade aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg 2022; 221:107369. [DOI: 10.1016/j.clineuro.2022.107369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 07/04/2022] [Accepted: 07/12/2022] [Indexed: 11/16/2022]
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Pan XH, Qiu K, Zhu FY, Shi HB, Liu S. Immediate postinterventional flat-panel CT: Differentiation of hemorrhagic transformation from contrast exudation of acute ischemic stroke patients after thrombectomy. Acta Radiol 2022; 64:1600-1607. [PMID: 36036263 DOI: 10.1177/02841851221122429] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Flat-panel computed tomography (CT) is an available imaging modality immediately after endovascular thrombectomy without transferring patients to the CT room. PURPOSE To determine the accuracy of flat-panel CT scans in differentiating hemorrhagic transformation (HT) from contrast exudation after thrombectomy in patients with acute ischemic stroke (AIS). MATERIAL AND METHODS From January 2019 to December 2021, consecutive patients with AIS who received an immediate flat-panel CT scan and follow-up neuroimaging after thrombectomy were enrolled in our study. The receiver operating characteristic curve was adopted to assess the discriminating accuracy of characteristics of flat-panel CT for HT. RESULTS A total of 108 patients were enrolled in the study; 58 (53.7%) patients presented with hyperdense lesions on flat-panel CT. Patients with hyperdense lesions experienced a higher proportion of HT than patients without (58.7% vs. 10.0%; P < 0.001). Among all patients with hyperdensity on flat-panel CT, patients who experienced HT had higher average Hounsfield units (HUavg) (125 vs. 93; P = 0.001) and a higher proportion of mass effect (67.6 vs. 12.5; P < 0.001). The flat-panel CT differentiating HT from contrast exudation yielded a sensitivity of 87.2% and a negative predictive value of 90.0%. The area under the curve of HUavg, mass effect, and combination for differentiation of HT were 0.74, 0.78, and 0.83, respectively. CONCLUSION The hyperdensity on immediately post-thrombectomy flat-panel CT could differentiate HT from contrast exudation with an excellent negative predictive value. The ability of flat-panel CT in differentiating HT from contrast exudation was improved when combined with HUavg and mass effect.
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Affiliation(s)
- Xiao-Hu Pan
- Department of Neurology, Xuyi People's Hospital, Xuyi, PR China
| | - Kai Qiu
- Department of Interventional Radiology, 74734The First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Fa-Yong Zhu
- Department of Neurology, Xuyi People's Hospital, Xuyi, PR China
| | - Hai-Bin Shi
- Department of Interventional Radiology, 74734The First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Sheng Liu
- Department of Interventional Radiology, 74734The First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
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Tzelnick S, Mizrachi A, Barkan N, Shivatzki S, Yosefof E, Hikri E, Attias J, Hilly O. The protective effect of aspirin-induced temporary threshold shift in an animal model of cisplatin-related ototoxicity. J Cancer Res Clin Oncol 2022; 149:2009-2016. [PMID: 35773430 DOI: 10.1007/s00432-022-04144-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/13/2022] [Indexed: 10/17/2022]
Abstract
PURPOSE The purpose of this study was to evaluate whether induction of temporary threshold shift (TTS) with aspirin prior to cisplatin exposure can prevent or minimize cisplatin detrimental effects on hearing. METHODS We randomly divided BALB mice into three groups: (1) cisplatin only, (2) aspirin only, and (3) combined aspirin/cisplatin. Cisplatin was administered as a single intraperitoneal injection of 14 mg/kg. Aspirin was administered for three weeks via intraperitoneal injection of 200 mg/kg sodium salicylate, twice daily. Air conduction thresholds were recorded using Auditory Brainstem Responses (ABR). Cochleae were harvested and cochlear hair cells were counted using a scanning electron microscope (SEM). RESULTS Aspirin-induced TTS have reached an average of 30.05±16.9 dB after 2 weeks. At 60 days, cisplatin-only treated mice experienced an average threshold shifts of 50.7 dB at 4 kHz, 35.16 dB at 8 kHz, 70 dB at 16 kHz, 53.1 dB at 32 kHz. All threshold shifts were significantly worse than for cisplatin/aspirin treated mice with TTS of 11.85 dB at 4 kHz, 3.58 dB at 8 kHz, 16.58 dB at 16 kHz, 20.41 dB at 32 kHz (p < 0.01). Cochlear cell count with SEM has shown reduction in the number of both inner and outer hair cells in the mid-turn in cisplatin treated mice. CONCLUSION Aspirin induced TTS can protect from cisplatin-induced ototoxicity. This beneficial effect was demonstrated by auditory thresholds as well as SEM. Larger pre-clinical and clinical studies are still needed to confirm these findings.
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Affiliation(s)
- Sharon Tzelnick
- Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel. .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Aviram Mizrachi
- Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Neta Barkan
- Institute of Audiology and Clinical Neurophysiology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Shaked Shivatzki
- Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eyal Yosefof
- Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Elad Hikri
- Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Joseph Attias
- Institute of Audiology and Clinical Neurophysiology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.,Department of Communications Sciences and Disorders, Haifa University, Haifa, Israel
| | - Ohad Hilly
- Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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21
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Wang X, Wehbe A, Kaura S, Chaudhry N, Geng X, Ding Y. Updates on Selective Brain Hypothermia: Studies From Bench Work to Clinical Trials. Front Neurol 2022; 13:899547. [PMID: 35599727 PMCID: PMC9120368 DOI: 10.3389/fneur.2022.899547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/13/2022] [Indexed: 12/01/2022] Open
Abstract
Thrombectomy or thrombolysis are the current standards of care for acute ischemic stroke (AIS), however, due to time constraints regarding operations and a multitude of contraindications, AIS remains one of the leading causes of death and chronic disability worldwide. In recent years, therapeutic hypothermia has been explored as an adjuvant therapy for AIS treatment and has shown potential to improve outcomes in patients with AIS. In particular, selective therapeutic hypothermia has shown to markedly reduce infarct volumes and have neuroprotective effects, while also minimizing many systemic side effects seen with systemic therapeutic hypothermia. Both preclinical and clinical trials have demonstrated that selective therapeutic hypothermia is a safe and feasible therapy for patients who have suffered an AIS. In this review, we summarize the current update on selective hypothermia through major studies that have been conducted in rodents, large animals, and clinical trials, and briefly discuss the prospects of selective hypothermic research. We hope this review helps facilitate the exploration of other possible adjuvant treatment modalities in the neuroprotection of ischemic stroke, whether upon symptom onset or after vascular recanalization.
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Affiliation(s)
- Xiaoyu Wang
- Department of Luhe Institute of Neuroscience, Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Alexandra Wehbe
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - Shawn Kaura
- Lake Erie College of Osteopathic Medicine at Seton Hill, Greensburg, PA, United States
| | - Naveed Chaudhry
- Lake Erie College of Osteopathic Medicine at Seton Hill, Greensburg, PA, United States
| | - Xiaokun Geng
- Department of Luhe Institute of Neuroscience, Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - Yuchuan Ding
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
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22
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Effectiveness of Combined Thrombolysis and Mild Hypothermia Therapy in Acute Cerebral Infarction: A Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:4044826. [PMID: 35469165 PMCID: PMC9034919 DOI: 10.1155/2022/4044826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 03/05/2022] [Accepted: 03/18/2022] [Indexed: 11/18/2022]
Abstract
Objective To evaluate the effectiveness and safety of thrombolytic therapy combined with mild hypothermia in patients with acute cerebral infarction (ACI), based on a meta-analysis of randomized controlled trials (RCTs). Methods PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure Database of Controlled Trials were systematically screened for randomized controlled trials (RCTs) of thrombolytic therapy combined with mild hypothermia in treating ACI from inception to January 2021. Participation and outcomes among intervention enrollees are as follows: P, participants (patients in ACI); I, interventions (thrombolysis in combination with mild hypothermia therapy); C, controls (thrombolysis merely); O, outcomes (main outcomes are the change of NIHSS, glutathione peroxidase, superoxide dismutase, malondialdehyde, inflammatory factor interleukin-1β, tumor necrosis factor-α, and adverse reaction). Following data extraction and quality assessment, a meta-analysis was performed using RevMan 5.3 software. Results A total of 26 RCTs involving 2071 patients were included. Compared to thrombolysis alone, thrombolytic therapy combined with mild hypothermia leads to better therapeutic efficacy [RR = 1.23, 95% CI (1.16, 1.31)], NIHSS [MD = -2.02, 95% CI (-2.55, -1.49)], glutathione peroxidase [MD = 8.71, 95% CI (5.55, 11.87)], superoxide dismutase [MD = 16.52, 95% CI (12.31, 19.74)], malondialdehyde [MD = -1.86, 95% CI (-1.98, -1.75)], interleukin-1β [MD = -3.48, 95% CI (-4.88, -2.08)], tumor necrosis factor-α [MD = -0.46, 95% CI (-3.39, 2.48)], and adverse reaction [RR = 0.87, 95% CI (0.63, 1.20)]. Conclusions Thrombolytic therapy combined with mild hypothermia demonstrates a beneficial role in reducing brain nerve function impairment and inflammatory reactions in ACI subjects analysed in this meta-analysis.
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23
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Recombinant Klotho Protein Ameliorates Myocardial Ischemia/Reperfusion Injury by Attenuating Sterile Inflammation. Biomedicines 2022; 10:biomedicines10040894. [PMID: 35453645 PMCID: PMC9032004 DOI: 10.3390/biomedicines10040894] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/31/2022] [Accepted: 04/08/2022] [Indexed: 02/01/2023] Open
Abstract
Currently, no effective therapy and potential target have been elucidated for preventing myocardial ischemia and reperfusion injury (I/R). We hypothesized that the administration of recombinant klotho (rKL) protein could attenuate the sterile inflammation in peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1). This hypothesis was examined using a rat coronary artery ligation model. Rats were divided into sham, sham+ rKL, I/R, and I/R+ rKL groups (n = 5/group). Administration of rKL protein reduced infarct volume and attenuated extracellular release of HMGB1 from peri-infarct tissue after myocardial I/R injury. The administration of rKL protein inhibited the expression of pro-inflammatory cytokines in the peri-infarct regions and significantly attenuated apoptosis and production of intracellular reactive oxygen species by myocardial I/R injury. Klotho treatment significantly reduced the increase in the levels of circulating HMGB1 in blood at 4 h after myocardial ischemia. rKL regulated the levels of inflammation-related proteins. This is the first study to suggest that exogenous administration of rKL exerts myocardial protection effects after I/R injury and provides new mechanistic insights into rKL that can provide the theoretical basis for clinical application of new adjunctive modality for critical care of acute myocardial infarction.
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24
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Carlstrom LP, Perry A, Graffeo CS, Dai D, Ding YH, Jakaitis DR, Lu A, Rodgers S, Kreck T, Hoofer K, Gorny KR, Kadirvel R, Kallmes DF. Novel Focal Therapeutic Hypothermia Device for Treatment of Acute Neurologic Injury: Large Animal Safety and Efficacy Trial. J Neurol Surg B Skull Base 2022; 83:203-209. [PMID: 35433184 PMCID: PMC9010132 DOI: 10.1055/s-0040-1721818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 09/11/2020] [Indexed: 10/22/2022] Open
Abstract
Objective Therapeutic hypothermia is a potentially powerful and controversial clinical tool for neuroprotection following acute neurologic pathology, particularly vascular injury. Indeed, therapeutic hypothermia remains a standard of care for postcardiac arrest ischemia and acute neonatal hypoxic-ischemic encephalopathy, improving both survival and outcomes. Although therapeutic hypothermia remains promising for cellular and systems-based neuronal protection in other neurologic injury states, the systemic side effects have limited clinical utility, confounded analysis of potential neurologic benefits, and precluded the completion of meaningful clinical trials. Methods To address such limitations, we developed and tested a novel, minimally invasive, neurocritical care device that employs continuous circulation of cold saline through the pharyngeal region to deliver focal cerebrovascular cooling. We conducted a preclinical safety and efficacy trial in six adult porcine animals to assess the validity and functionality of the NeuroSave device, and assess cooling potential following middle cerebral artery occlusion ( n = 2). Results NeuroSave consistently lowered brain parenchymal temperature by a median of 9°C relative to core temperature within 60 minutes of initiation, including in ischemic cerebral parenchyma. The core body temperature experienced a maximal reduction of 2°C, or 5% of body temperature, with no associated adverse effects identified. Conclusion The present study uses a large animal preclinical model to demonstrate the safety and efficacy of a novel, noninvasive device for the induction of robust and systemically safe hypothermia within the brain.
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Affiliation(s)
- Lucas P. Carlstrom
- Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, United States
| | - Avital Perry
- Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, United States
| | | | - Daying Dai
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
| | - Yong H. Ding
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
| | - Daniel R. Jakaitis
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
| | - Aiming Lu
- Department of Medical Physics, Mayo Clinic, Rochester, Minnesota, United States
| | - Seth Rodgers
- NeuroSave Inc., San Francisco, California, United States
| | - Thomas Kreck
- NeuroSave Inc., San Francisco, California, United States
| | - Kelly Hoofer
- NeuroSave Inc., San Francisco, California, United States
| | - Krzysztof R. Gorny
- Department of Medical Physics, Mayo Clinic, Rochester, Minnesota, United States
| | | | - David F. Kallmes
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
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25
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Liu C, Xie J, Sun S, Li H, Li T, Jiang C, Chen X, Wang J, Le A, Wang J, Li Z, Wang J, Wang W. Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke. Cell Mol Neurobiol 2022; 42:621-646. [PMID: 33125600 PMCID: PMC11441267 DOI: 10.1007/s10571-020-00985-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 10/22/2020] [Indexed: 12/17/2022]
Abstract
Hemorrhagic transformation (HT) is a common complication after thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in ischemic stroke. In this article, recent research progress of HT in vivo and in vitro studies was reviewed. We have discussed new potential mechanisms and possible experimental models of HT development, as well as possible biomarkers and treatment methods. Meanwhile, we compared and analyzed rodent models, large animal models and in vitro BBB models of HT, and the limitations of these models were discussed. The molecular mechanism of HT was investigated in terms of BBB disruption, rt-PA neurotoxicity and the effect of neuroinflammation, matrix metalloproteinases, reactive oxygen species. The clinical features to predict HT were represented including blood biomarkers and clinical factors. Recent progress in neuroprotective strategies to improve HT after stroke treated with rt-PA is outlined. Further efforts need to be made to reduce the risk of HT after rt-PA therapy and improve the clinical prognosis of patients with ischemic stroke.
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Affiliation(s)
- Chengli Liu
- Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China
| | - Jie Xie
- Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China
| | - Shanshan Sun
- Department of Ultrasound Imaging, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China
| | - Hui Li
- Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China
| | - Tianyu Li
- Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China
| | - Chao Jiang
- Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China
| | - Xuemei Chen
- Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Henan, 450000, People's Republic of China
| | - Junmin Wang
- Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Henan, 450000, People's Republic of China
| | - Anh Le
- Washington University in St. Louis, Saint Louis, MO, 63130, USA
| | - Jiarui Wang
- The Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Zhanfei Li
- Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China
| | - Jian Wang
- Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Henan, 450000, People's Republic of China.
| | - Wei Wang
- Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
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26
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Honig A, Percy J, Sepehry AA, Gomez AG, Field TS, Benavente OR. Hemorrhagic Transformation in Acute Ischemic Stroke: A Quantitative Systematic Review. J Clin Med 2022; 11:jcm11051162. [PMID: 35268253 PMCID: PMC8910828 DOI: 10.3390/jcm11051162] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 02/13/2022] [Accepted: 02/17/2022] [Indexed: 02/06/2023] Open
Abstract
The prevalence and risk factors of hemorrhagic transformation (HT) after acute ischemic stroke HT have not been adequately delineated. We performed a systematic review and meta-analysis to identify English-language prospective observational MEDLINE and EMBASE-listed reports of acute ischemic stroke with HT published from 1985–2017. Studies that used the ECASS-2 definitions of hemorrhagic transformation subtypes, hemorrhagic infarction (HI), and parenchymal hematoma (PH) were included. Patients treated with intravenous thrombolysis with tissue plasminogen activator (IV-tPA) were compared with those who did not receive thrombolysis. A total of 65 studies with 17,259 patients met inclusion criteria. Overall, HT prevalence was 27%; 32% in patients receiving IV-tPA vs. 20% in those without. Overall PH prevalence was 9%; 12% in IV-tPA treated patients vs. 5% in those without. HT was associated with a history of atrial fibrillation (OR 2.94) and use of anticoagulants (OR 2.47). HT patients had higher NIHSS (Hedge’s-G 0.96) and larger infarct volume (diffusion-weighted MRI, Hedge’s-G 0.8). In IV-tPA treated patients, PH correlated with antiplatelet (OR 3) and statin treatment (OR 4). HT (OR 3) and PH (OR 8) were associated with a poor outcome at 90-day (mRS 5–6). Hemorrhagic transformation is a frequent complication of acute ischemic stroke and is associated with poor outcome. Recognition of risk factors for HT and PH may reduce their incidence and severity.
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Affiliation(s)
- Asaf Honig
- Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (J.P.); (A.A.S.); (A.G.G.); (T.S.F.); (O.R.B.)
- Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
- Correspondence:
| | - Jennifer Percy
- Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (J.P.); (A.A.S.); (A.G.G.); (T.S.F.); (O.R.B.)
| | - Amir A. Sepehry
- Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (J.P.); (A.A.S.); (A.G.G.); (T.S.F.); (O.R.B.)
- Clinical Psychology Program, Adler University, Vancouver, BC V6B 3J5, Canada
| | - Alejandra G. Gomez
- Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (J.P.); (A.A.S.); (A.G.G.); (T.S.F.); (O.R.B.)
| | - Thalia S. Field
- Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (J.P.); (A.A.S.); (A.G.G.); (T.S.F.); (O.R.B.)
| | - Oscar R. Benavente
- Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (J.P.); (A.A.S.); (A.G.G.); (T.S.F.); (O.R.B.)
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27
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Kim JY, Kim JH, Park J, Beom JH, Chung SP, You JS, Lee JE. Targeted Temperature Management at 36 °C Shows Therapeutic Effectiveness via Alteration of Microglial Activation and Polarization After Ischemic Stroke. Transl Stroke Res 2022; 13:132-141. [PMID: 33893993 DOI: 10.1007/s12975-021-00910-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 02/03/2021] [Accepted: 04/12/2021] [Indexed: 02/02/2023]
Abstract
Ischemic injury leads to cell death and inflammatory responses after stroke. Microglia especially play a crucial role in this brain inflammation. Targeted temperature management (TTM) at 33 °C has shown neuroprotective effects against many acute ischemic injuries. However, it has also shown some adverse effects in preclinical studies. Therefore, we explored the neuroprotective effect of TTM at 36 °C in the ischemic brain. To confirm the neuroprotective effects of hypothermia, mice were subjected to a permanent stroke and then treated with one of the TTM paradigms at 33 and 36 °C. For comparison of TTM at 33 and 36 °C, we examined neuronal cell death and inflammatory response, including activation and polarization of microglia in the ischemic brain. TTM at 33 and 36 °C showed neuroprotective effects in comparison with normal body temperature (NT) at 37.5 °C. Mice under TTM at 33 and 36 °C showed ~ 45-50% fewer TUNEL-positive cells than those under NT. In IVIS spectrum CT, the activation of microglia/macrophage in CX3CR1GFP mice reduced after TTM at 33 and 36 °C in comparison with that after NT on day 7 after ischemic stroke. The number of Tmem119-positive cells under TTM at 33 and 36 °C was ~ 45-50% lower than that in mice under NT. TTM at 33 and 36 °C also increased the ratio of CD206-/CD86-positive cells than the ratio of CD86-/CD206-positive cells by ~ 1.2-fold. Thus, TTM at 33 and 36 °C could equivalently decrease the expression of certain cytokines after ischemic stroke. Our study suggested that TTM at 33 or 36 °C produces equivalent neuroprotective effects by attenuating cell death and by altering microglial activation and polarization. Therefore, TTM at 36 °C can be considered for its safety and effectiveness in ischemic stroke.
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Affiliation(s)
- Jong Youl Kim
- Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ju Hee Kim
- Department of Emergency Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of Korea
| | - Joohyun Park
- Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin Ho Beom
- Department of Emergency Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of Korea
| | - Sung Phil Chung
- Department of Emergency Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of Korea
| | - Je Sung You
- Department of Emergency Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of Korea.
| | - Jong Eun Lee
- Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea.
- BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro Seodaemun-gu, Medical School Building Room # 146, Seoul, 03722, Republic of Korea.
- Brain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Li W, Cao F, Takase H, Arai K, Lo EH, Lok J. Blood-Brain Barrier Mechanisms in Stroke and Trauma. Handb Exp Pharmacol 2022; 273:267-293. [PMID: 33580391 DOI: 10.1007/164_2020_426] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
The brain microenvironment is tightly regulated. The blood-brain barrier (BBB), which is composed of cerebral endothelial cells, astrocytes, and pericytes, plays an important role in maintaining the brain homeostasis by regulating the transport of both beneficial and detrimental substances between circulating blood and brain parenchyma. After brain injury and disease, BBB tightness becomes dysregulated, thus leading to inflammation and secondary brain damage. In this chapter, we overview the fundamental mechanisms of BBB damage and repair after stroke and traumatic brain injury (TBI). Understanding these mechanisms may lead to therapeutic opportunities for brain injury.
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Affiliation(s)
- Wenlu Li
- Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Fang Cao
- Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Hajime Takase
- Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Ken Arai
- Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Eng H Lo
- Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
| | - Josephine Lok
- Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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29
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Gonzales NR, Grotta JC. Pharmacologic Modification of Acute Cerebral Ischemia. Stroke 2022. [DOI: 10.1016/b978-0-323-69424-7.00057-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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30
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Hong JM, Kim DS, Kim M. Hemorrhagic Transformation After Ischemic Stroke: Mechanisms and Management. Front Neurol 2021; 12:703258. [PMID: 34917010 PMCID: PMC8669478 DOI: 10.3389/fneur.2021.703258] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 10/21/2021] [Indexed: 01/01/2023] Open
Abstract
Symptomatic hemorrhagic transformation (HT) is one of the complications most likely to lead to death in patients with acute ischemic stroke. HT after acute ischemic stroke is diagnosed when certain areas of cerebral infarction appear as cerebral hemorrhage on radiological images. Its mechanisms are usually explained by disruption of the blood-brain barrier and reperfusion injury that causes leakage of peripheral blood cells. In ischemic infarction, HT may be a natural progression of acute ischemic stroke and can be facilitated or enhanced by reperfusion therapy. Therefore, to balance risks and benefits, HT occurrence in acute stroke settings is an important factor to be considered by physicians to determine whether recanalization therapy should be performed. This review aims to illustrate the pathophysiological mechanisms of HT, outline most HT-related factors after reperfusion therapy, and describe prevention strategies for the occurrence and enlargement of HT, such as blood pressure control. Finally, we propose a promising therapeutic approach based on biological research studies that would help clinicians treat such catastrophic complications.
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Affiliation(s)
- Ji Man Hong
- Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon-si, South Korea
- Department of Biomedical Science, Ajou University School of Medicine, Ajou University Medical Center, Suwon-si, South Korea
| | - Da Sol Kim
- Department of Biomedical Science, Ajou University School of Medicine, Ajou University Medical Center, Suwon-si, South Korea
| | - Min Kim
- Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon-si, South Korea
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31
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Ushio A, Eto K. The Expression of the Cold Shock Protein RNA Binding Motif Protein 3 is Transcriptionally Responsive to Organ Temperature in Mice. Protein Pept Lett 2021; 28:270-275. [PMID: 32972335 DOI: 10.2174/0929866527666200924144424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/19/2020] [Accepted: 08/21/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Mild hypothermia, i.e. maintenance of organ temperature by up to 8°C lower than body temperature, is a critical strategy for exerting some functions of the cells and organs normally, and is an useful therapy for recovering properly from some diseases, including myocardial infarction, cardiac arrest, brain injury, and ischemic stroke. Nevertheless, there were no focusses so far on organ temperature and potential responses of gene expression to organ temperature in organs of homeothermic animals that survive under normal conditions. OBJECTIVE The present study aimed to assess organ temperature in homeothermic animals and evaluate the effect of their organ temperature on the expression of the cold shock protein RNA binding motif protein 3 (RBM3), and to gain insights into the organ temperature-mediated regulation of RBM3 gene transcription via Nuclear factor β-light-chain-enhancer of activated B cells (NF-κB) p65, which had been identified as a transcription factor that is activated by undergoing the Ser276 phosphorylation and promotes the RBM3 gene expression during mild hypothermia. METHODS We measured the temperature of several organs, where RBM3 expression was examined, in female and male mice. Next, in male mice, we tested NF-κB p65 expression and its Ser276 phosphorylation in organs that have their lower temperature than body temperature and compared them with those in organs that have their temperature near body temperature. RESULTS Organ temperature was around 32°C in the brain and reproductive organs, which is lower than the body temperature, and around 37°C in the heart, liver, and kidney, which is comparable to the body temperature. The expression of RBM3 was detected greatly in the brain and reproductive organs with their organ temperature of around 32°C, and poorly in the heart, liver, and kidney with their organ temperature of around 37°C. In accordance with the changes in the RBM3 expression, the NF-κB p65 Ser276 phosphorylation was detected more greatly in the testis and brain with their organ temperature of around 32°C, than in the heart, liver, and kidney with their organ temperature of around 37°C, although the NF-κB p65 expression was unchanged among all the organs tested. DISCUSSION Our data suggested that organ temperature lower than body temperature causes the expression of RBM3 in the brain and reproductive organs of mice, and that lower organ temperature causes the NF-κB p65 activation through the Ser276 phosphorylation, resulting in an increase in the RBM3 gene transcription, in the brain and reproductive organs of mice. CONCLUSION The study may present the possibility that organ temperature-induced alterations in gene expression are organ specific in homeotherms and the possibility that organ temperature-induced alterations in gene expression are transcriptionally regulated in some organs of homeotherms.
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Affiliation(s)
- Ayako Ushio
- Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan
| | - Ko Eto
- Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan
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Qu X, Shang F, Zhao H, Qi M, Cheng W, Xu Y, Jiang L, Chen W, Wang N, Zhang H. Targeted temperature management at 33 degrees Celsius in patients with high-grade aneurysmal subarachnoid hemorrhage: a protocol for a multicenter randomized controlled study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:581. [PMID: 33987279 DOI: 10.21037/atm-20-4719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background Studies on the use of therapeutic hypothermia (TH) to improve the outcome of high-grade aneurysmal subarachnoid hemorrhage (aSAH), show promising, though conflicting results because of the lack of high-quality trials. The aim of this study is to evaluate the safety and efficacy of TH (maintaining bladder temperature at 33 °C for ≥72 h) to treat patients with high-grade aSAH (Hunt-Hess grade IV-V). Methods A multicenter, randomized, controlled clinical trial will be conducted for October 2020 to September 2024 involving 10 clinics. Patients who meet the inclusion criteria will be randomized 1:1 to a TH group and a normothermia group. The trial will enroll 96 participants in TH group and normothermia one, respectively. The trial was registered with ClinicalTrials.gov (NCT03442608) on February 22, 2018. Following conventional treatment for aSAH, patients will undergo either TH for at least 72 h or normothermia. The primary endpoint is the Glasgow outcome scale at 6 months after bleeding. The secondary endpoints are: (I) mortality at 6 months after bleeding; (II) intracranial pressure; (III) intensive care unit stay; and (IV) hospital stay. The safety endpoints include neurological, infectious, intestinal, circulatory, coagulation, and bleeding complications, electrolyte disorders, and other complications. Discussion If the study hypothesis is confirmed, TH at 33 °C in patients with high-grade aSAH may become a promising treatment strategy for improving 6-month outcome. Trial registration The trial has been registered at ClinicalTrials.gov (ID: NCT03442608).
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Affiliation(s)
- Xin Qu
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Feng Shang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Hao Zhao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Meng Qi
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Weitao Cheng
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yueqiao Xu
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Lidan Jiang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Wenjing Chen
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Ning Wang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Hongqi Zhang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
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Lee JS, Hwang YH, Sohn SI. Factors Contributing to an Efficacious Endovascular Treatment for Acute Ischemic Stroke in Asian Population. Neurointervention 2021; 16:91-110. [PMID: 33765729 PMCID: PMC8261106 DOI: 10.5469/neuroint.2020.00339] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 02/19/2021] [Indexed: 12/13/2022] Open
Abstract
Although randomized control trials about endovascular treatment (EVT) of emergent large vessel occlusion (LVO) have demonstrated the success of mechanical thrombectomy as the choice of treatment, a wide range of caveats remain unaddressed. Asian patients were rarely included in the trials, thereby raising the question of whether the treatment could be generalized. In addition, there remains a concern on the feasibility of the method with respect to its application against intracranial atherosclerosis (ICAS)-related LVO, frequently observed in the Asian population. It is important to include evidence on ICAS LVO from Asian countries in the future for a comprehensive understanding of LVO etiology. Besides the issues with EVT, prognostic concerns in diabetes patients, acute kidney injury following EVT, neuroprotective management against reperfusion injury, and other peri-EVT issues should be considered in clinical practice. In the current article, we present an in-depth review of the literature that revises information pertaining to such concerns.
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Affiliation(s)
- Jin Soo Lee
- Department of Neurology, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Yang-Ha Hwang
- Department of Neurology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Sung-Il Sohn
- Department of Neurology, Keimyung University Dongsan Hospital, Kyemyung University School of Medicine, Daegu, Korea
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Prognostic significance of early pyrexia in acute intracerebral haemorrhage: The INTERACT2 study. J Neurol Sci 2021; 423:117364. [PMID: 33647734 DOI: 10.1016/j.jns.2021.117364] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 01/25/2021] [Accepted: 02/18/2021] [Indexed: 11/23/2022]
Abstract
INTRODUCTION Uncertainty exists over the prognostic significance of pyrexia in acute intracerebral haemorrhage (ICH). We aimed to determine the association of elevated body temperature with clinical and imaging outcomes among participants of the main Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2). METHODS Post-hoc analyses of INTERACT2, an international open, blinded outcome assessed, randomised trial of 2839 patients with spontaneous ICH (<6 h of onset) and elevated systolic blood pressure (SBP, 150-220 mmHg) randomly assigned to intensive (SBP target <140 mmHg) or guideline-recommended (SBP target < 180 mmHg) BP management. Multivariable logistic regression was used to determine associations of elevated baseline body temperature (<37.5 vs. ≥37.5 °C) and 90-day clinical outcome defined on the modified Rankin scale (mRS). Analysis of covariance determined relations of body temperature and haematoma and perihaematomal oedema (PHE) volumes, at baseline and 24 h post-randomisation. RESULTS Of 2792 participants with data available at admission, 39 (1.4%) patients had elevated body temperature ≥ 37.5 °C. Elevated body temperature was significantly associated with 90-day mortality (adjusted odds ratio 2.44; 95% confidence interval 1.02-5.82; P = .044) but not with major disability alone (mRS scores 3-5) and combination death or major disability (mRS scores 3-6). Elevated body temperature was also associated with larger PHE volume at baseline (10.89 vs. 3.14 cm3, P < .001;) and 24 h (12.43 vs 5.76 cm3, P = .018) but not with haematoma volumes at these time points. CONCLUSION Early pyrexia in mild to moderate ICH is associated with greater mortality and larger PHE volume, suggesting an early inflammatory-mediated reaction. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov (NCT00716079).
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Rosahl SC, Covarrubias C, Wu JH, Urquieta E. Staying Cool in Space: A Review of Therapeutic Hypothermia and Potential Application for Space Medicine. Ther Hypothermia Temp Manag 2021; 12:115-128. [PMID: 33617356 DOI: 10.1089/ther.2020.0041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Despite rigorous health screenings, medical incidents during spaceflight missions cannot be avoided. With long-duration exploration flights on the rise, the likelihood of critical medical conditions with no suitable treatment on board will increase. Therapeutic hypothermia (TH) could serve as a bridge treatment in space prolonging survival and reducing neurological damage in ischemic conditions such as stroke and cardiac arrest. We conducted a review of published studies to determine the potential and challenges of TH in space based on its physiological effects, the cooling methods available, and clinical evidence on Earth. Currently, investigators have found that application of low normothermia leads to better outcomes than mild hypothermia. Data on the impact of hypothermia on a favorable neurological outcome are inconclusive due to lack of standardized protocols across hospitals and the heterogeneity of medical conditions. Adverse effects with systemic cooling are widely reported, and could be reduced through selective brain cooling and pharmacological cooling, promising techniques that currently lack clinical evidence. We hypothesize that TH has the potential for application as supportive treatment for multiple medical conditions in space and recommend further investigation of the concept in feasibility studies.
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Affiliation(s)
- Sophie C Rosahl
- Faculty of Medicine, Ruprecht-Karls-Universität, Heidelberg, Germany
| | - Claudia Covarrubias
- School of Medicine, Universidad Anáhuac Querétaro, Santiago de Querétaro, México
| | - Jimmy H Wu
- Department of Medicine and Center for Space Medicine, Baylor College of Medicine, Houston, Texas, USA.,Translational Research Institute for Space Health, Houston, Texas, USA
| | - Emmanuel Urquieta
- Translational Research Institute for Space Health, Houston, Texas, USA.,Department of Emergency Medicine and Center for Space Medicine, Baylor College of Medicine, Houston, Texas, USA
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Sultan S, Acharya Y, Barrett N, Hynes N. A pilot protocol and review of triple neuroprotection with targeted hypothermia, controlled induced hypertension, and barbiturate infusion during emergency carotid endarterectomy for acute stroke after failed tPA or beyond 24-hour window of opportunity. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1275. [PMID: 33178807 PMCID: PMC7607101 DOI: 10.21037/atm-2020-cass-14] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
An alternative to tissue plasminogen activator (tPA) failure has been a daunting challenge in ischemic stroke management. As tPA is time-dependent, delays can occur in definitive treatment while passively waiting to observe a clinical response to intravenous thrombolysis. Until today, uncertainty exists in the management strategy of wake-up stroke patients or those presenting beyond the therapeutic tPA window. Clinical dilemmas in these situations can prolong the transitional period of inertia, resulting in an adverse neurological outcome. We propose and review an innovative approach called triple neuro-protection (TNP), which encompasses three technical domains-targeted hypothermia, systemic induced hypertension, and barbiturates infusion, to protect the brain during carotid endarterectomy after failed tPA and/or beyond the 24-hour therapeutic mechanical thrombectomy window. This proposal assimilates discussion on the clinical evidence of the individual domains of TNP with our own clinical experience with TNP. Our first TNP was successfully employed in a 55-year-old man in 2015 while performing emergency carotid endarterectomy after he was referred to us 72 hours post tPA failure. The patient had a successful clinical outcome despite being in therapeutic inertia with 90–99% ipsilateral carotid stenosis and contralateral occlusion on presentation. In the last five years, we have safely used TNP in 25 selected cases with favourable clinical outcomes.
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Affiliation(s)
- Sherif Sultan
- Western Vascular Institute, Department of Vascular and Endovascular Surgery, University Hospital Galway, National University of Ireland, Galway, Ireland.,Department of Vascular & Endovascular Surgery, Galway Clinic, Royal College of Surgeons of Ireland/National University of Ireland Affiliated Teaching Hospitals, Doughiska, Galway, Ireland
| | - Yogesh Acharya
- Western Vascular Institute, Department of Vascular and Endovascular Surgery, University Hospital Galway, National University of Ireland, Galway, Ireland
| | - Nora Barrett
- Western Vascular Institute, Department of Vascular and Endovascular Surgery, University Hospital Galway, National University of Ireland, Galway, Ireland
| | - Niamh Hynes
- Department of Vascular & Endovascular Surgery, Galway Clinic, Royal College of Surgeons of Ireland/National University of Ireland Affiliated Teaching Hospitals, Doughiska, Galway, Ireland
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Lee SJ, Choi MH, Lee SE, Park JH, Park B, Lee JS, Hong JM. Optic nerve sheath diameter change in prediction of malignant cerebral edema in ischemic stroke: an observational study. BMC Neurol 2020; 20:354. [PMID: 32962645 PMCID: PMC7510108 DOI: 10.1186/s12883-020-01931-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 09/14/2020] [Indexed: 12/28/2022] Open
Abstract
Background In acute large anterior circulation infarct patients with large core volume, we evaluated the role of optic nerve sheath diameter (ONSD) change rates in prediction of malignant progression. Methods We performed a retrospective observational study including patients with anterior circulation acute ischemic stroke with large ischemic cores from January 2010 to October 2017. Primary outcome was defined as undergoing decompressive surgery or death due to severe cerebral edema, and termed malignant progression. Patients were divided into malignant progressors and nonprogressors. Malignant progression was divided into early progression that occurred before D1 CT, and late progression that occurred afterwards. Retrospective analysis of changes in mean ONSD/eyeball transverse diameter (ETD) ratio, and midline shifting (MLS) were evaluated on serial computed tomography (CT). Through analysis of CT at baseline, postprocedure, and at D1, the predictive ability of time based change in ONSD/ETD ratio in predicting malignant progression was evaluated. Results A total of 58 patients were included. Nineteen (32.8%) were classified as malignant; 12 early, and 7 late progressions. In analysis of CTpostprocedure, A 1 mm/hr. rate of change in MLS during the CTbaseline-CTpostprocedure time phase lead to a 6.7 fold increased odds of early malignant progression (p < 0.05). For ONSD/ETD, 1%/hr. change lead to a 1.6 fold increased odds, but this association was trending (p = 0.249). In the CTD1, 1%/day change of ONSD/ETD in the CTbaseline-CTD1 time phase lead to a 1.4 fold increased odds of late malignant progression (p = 0.021) while 1 mm/day rate of change in MLS lead to a 1.5 fold increased odds (p = 0.014). Conclusions The rate of ONSD/ETD changes compared to baseline at D1 CT can be a predictor of late malignant progression along with MLS. ONSD/ETD change rates evaluated at postprocedure did not predict early malignant progression.
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Affiliation(s)
- Seong-Joon Lee
- Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, Republic of Korea
| | - Mun Hee Choi
- Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, Republic of Korea
| | - Sung Eun Lee
- Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, Republic of Korea
| | - Ji Hyun Park
- Office of Biostatistics, Medical Research Collaborating Center, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Republic of Korea
| | - Bumhee Park
- Office of Biostatistics, Medical Research Collaborating Center, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Republic of Korea.,Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Jin Soo Lee
- Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, Republic of Korea
| | - Ji Man Hong
- Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, Republic of Korea.
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The Clinical Usefulness of Targeted Temperature Management in Acute Ischemic Stroke with Malignant Trait After Endovascular Thrombectomy. Neurocrit Care 2020; 34:990-999. [PMID: 32812197 DOI: 10.1007/s12028-020-01069-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/27/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND/OBJECTIVE Targeted temperature management (TTM) may be more beneficial after endovascular treatment (EVT) in patients with a large ischemic core. Therefore, we assessed the usefulness of TTM for such patients from a multicenter endovascular registry. METHODS Anterior circulation stroke patients who underwent endovascular recanalization were included; acute ischemic stroke with malignant traits was designated as (1) baseline Alberta Stroke Program Early CT Score (ASPECTS) below 6 and (2) diffusion-weighted imaging (DWI) lesion volume measurement (> 82 ml) or National Institutes of Health Stroke Scale score > 20 and item Ia > 0. TTM (34.5 °C) was maintained for at least 48 h. RESULTS We evaluated baseline demographics, risk factors, EVT parameters, and clinical outcomes between the TTM and non-TTM groups. Among the 548 patients, the TTM group (n = 91) significantly had a lower baseline ASPECTS (p < 0.001) and a higher DWI volume (p < 0.001) than the non-TTM group (n = 457). TTM group had a lower prevalence of favorable outcome (0-2 of modified Rankin Scale at 3 months; p = 0.008) than the non-TTM group. In a subgroup analysis of malignant trait patients (n = 80), TTM patients (n = 28) had more favorable outcome (32.1% vs. 7.7% p = 0.009) and less hemorrhagic transformation (none vs. any hemorrhage, p = 0.007) than non-TTM patients (n = 52). After adjusting for potential outcome predictors, TTM (odds ratio [OR] 4.63; confidence interval [CI] 1.20-17.89; p = 0.026) and hypertension (OR 0.18; CI 0.04-0.74; p = 0.018) were found to be independent determinants. CONCLUSIONS Our data suggest that TTM attenuates impending hemorrhagic transformation and leads to favorable clinical outcomes in EVT patients with malignant trait.
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Ageing as a risk factor for cerebral ischemia: Underlying mechanisms and therapy in animal models and in the clinic. Mech Ageing Dev 2020; 190:111312. [PMID: 32663480 DOI: 10.1016/j.mad.2020.111312] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/24/2020] [Accepted: 07/06/2020] [Indexed: 12/12/2022]
Abstract
Age is the only one non-modifiable risk of cerebral ischemia. Advances in stroke medicine and behavioral adaptation to stroke risk factors and comorbidities was successful in decreasing stroke incidence and increasing the number of stroke survivors in western societies. Comorbidities aggravates the outcome after cerebral ischemia. However, due to the increased in number of elderly, the incidence of stroke has increased again paralleled by an increase in the number of stroke survivors, many with severe disabilities, that has led to an increased economic and social burden in society. Animal models of stroke often ignore age and comorbidities frequently associated with senescence. This might explain why drugs working nicely in animal models fail to show efficacy in stroke survivors. Since stroke afflicts mostly the elderly comorbid patients, it is highly desirable to test the efficacy of stroke therapies in an appropriate animal stroke model. Therefore, in this review, we make parallels between animal models of stroke und clinical data and summarize the impact of ageing and age-related comorbidities on stroke outcome.
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Wu D, Chen J, Hussain M, Wu L, Shi J, Wu C, Ma Y, Zhang M, Yang Q, Fu Y, Duan Y, Ma C, Yan F, Zhu Z, He X, Yao T, Song M, Zhi X, Wang C, Cai L, Li C, Li S, Zhang Y, Ding Y, Ji X. Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status. J Cereb Blood Flow Metab 2020; 40:1415-1426. [PMID: 32126876 PMCID: PMC7308521 DOI: 10.1177/0271678x20903697] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes - complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.
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Affiliation(s)
- Di Wu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
| | - Jian Chen
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Mohammed Hussain
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
| | - Longfei Wu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China
| | - Jingfei Shi
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Chuanjie Wu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China
| | - Yanhui Ma
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Mo Zhang
- Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Qi Yang
- Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yongjuan Fu
- Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yunxia Duan
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Cui Ma
- Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Feng Yan
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zixin Zhu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xiaoduo He
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Tianqi Yao
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Ming Song
- Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Xinglong Zhi
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Chunxiu Wang
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Lipeng Cai
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Chuanhui Li
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Shengli Li
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yongbiao Zhang
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Yuchuan Ding
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.,Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
| | - Xunming Ji
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
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Safety of Triple Neuroprotection with Targeted Hypothermia, Controlled Induced Hypertension, and Barbiturate Infusion during Emergency Carotid Endarterectomy for Acute Stroke after Missing the 24 Hours Window Opportunity. Ann Vasc Surg 2020; 69:163-173. [PMID: 32473308 DOI: 10.1016/j.avsg.2020.05.041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 04/30/2020] [Accepted: 05/02/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND The aim of this study is to establish the initial safety of triple neuroprotection (TNP) in an acute stroke setting in patients presenting outside the window for systemic tissue plasminogen activator (tPA). METHODS Over 12,000 patients were referred to our vascular services with carotid artery disease, of whom 832 had carotid intervention with a stroke rate of 0.72%. Of these, 25 patients presented (3%), between March 2015 and 2019, with acute dense stroke. These patients had either failed tPA or passed the recommended timing for acute stroke intervention. Fifteen (60%) had hemi-neglect with evidence of acute infarct on magnetic resonance imaging of the brain and a Rankin score of 4 or 5. Ninety-six percent had an 80-99% stenosis on the symptomatic side. Mean ABCD3-I score was 11.35. All patients underwent emergency carotid endarterectomy (CEA) with therapeutically induced hypothermia (32-34°C), targeted hypertension (systolic blood pressure 180-200 mm Hg), and brain suppression with barbiturate. RESULTS There were no cases of myocardial infarction, death, cranial nerve injury, wound hematoma, or procedural bleeding. Mean hospital stay was 8.4 (±9.5) days. All cases had resolution of neurological symptoms, except 3 who had failed previous thrombolysis. Eighty percent had a postoperative Rankin score of 0 on discharge and 88% of patients were discharged home with 3 requiring rehabilitation. CONCLUSIONS Positive neurological outcomes and no serious adverse events were observed using TNP during emergency CEA in patients with acute brain injury. We recommend TNP for patients who are at an increased risk of stroke perioperatively, or who have already suffered from an acute stroke beyond the recommended window of 24 hr. Certainly, the positive outcomes are not likely reproducible outside of high-volume units and patients requiring this surgery should be transferred to experienced surgeons in appropriate tertiary referral centers.
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Kuczynski AM, Marzoughi S, Al Sultan AS, Colbourne F, Menon BK, van Es ACGM, Berez AL, Goyal M, Demchuk AM, Almekhlafi MA. Therapeutic Hypothermia in Acute Ischemic Stroke-a Systematic Review and Meta-Analysis. Curr Neurol Neurosci Rep 2020; 20:13. [PMID: 32372297 DOI: 10.1007/s11910-020-01029-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Therapeutic hypothermia (TH) in stroke demonstrates robust neuroprotection in animals but clinical applications remain controversial. We assessed current literature on the efficacy of TH in ischemic stroke. RECENT FINDINGS We conducted a meta-analysis comparing TH versus controls in studies published until June 2019. Controlled studies reporting on ≥ 10 adults with acute ischemic stroke were included. Primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2). Twelve studies (n = 351 TH, n = 427 controls) were included. Functional independence did not differ between groups (RR 1.17, 95% CI 0.93-1.46, random-effects p = 0.2). Five studies reported individual mRS outcomes and demonstrated a shift toward better outcome with TH (unadjusted cOR 1.57, 95% CI 1.01-2.44, p = 0.05). Overall complications were higher with TH (RR 1.18, 95% CI 1.06-1.32, p < 0.01). We did not observe an overall beneficial effect of TH in this analysis although some studies showed a shift toward better outcome. TH was associated with increased complications.
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Affiliation(s)
| | - Sina Marzoughi
- Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | | | | | - Bijoy K Menon
- Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Department of Clinical Neurosciences, Hotchkiss Brain Institute, Calgary, AB, Canada
| | - Adriaan C G M van Es
- Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands
| | | | - Mayank Goyal
- Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Department of Radiology, University of Calgary, Calgary, AB, Canada
| | - Andrew M Demchuk
- Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Department of Clinical Neurosciences, Hotchkiss Brain Institute, Calgary, AB, Canada
| | - Mohammed A Almekhlafi
- Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. .,Department of Clinical Neurosciences, Hotchkiss Brain Institute, Calgary, AB, Canada.
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Abstract
Despite thousands of neuroprotectants demonstrating promise in preclinical trials, a neuroprotective therapeutic has yet to be approved for the treatment of acute brain injuries such as stroke or traumatic brain injury. Developing a more detailed understanding of models and populations demonstrating "neurological resilience" in spite of brain injury can give us important insights into new translational therapies. Resilience is the process of active adaptation to a stressor. In the context of neuroprotection, models of preconditioning and unique animal models of extreme physiology (such as hibernating species) reliably demonstrate resilience in the laboratory setting. In the clinical setting, resilience is observed in young patients and can be found in those with specific genetic polymorphisms. These important examples of resilience can help transform and extend the current neuroprotective framework from simply countering the injurious cascade into one that anticipates, monitors, and optimizes patients' physiological responses from the time of injury throughout the process of recovery. This review summarizes the underpinnings of key adaptations common to models of resilience and how this understanding can be applied to new neuroprotective approaches.
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Affiliation(s)
- Neel S Singhal
- Department of Neurology, University of California-San Francisco, 555 South Mission Bay Blvd, San Francisco, CA, 94158, USA.
| | - Chung-Huan Sun
- Department of Neurology, University of California-San Francisco, 555 South Mission Bay Blvd, San Francisco, CA, 94158, USA
| | - Evan M Lee
- Cardiovascular Research Institute, University of California-San Francisco, 555 South Mission Bay Blvd, San Francisco, CA, 94158, USA
- Department of Physiology, University of California-San Francisco, 555 South Mission Bay Blvd, San Francisco, CA, 94158, USA
| | - Dengke K Ma
- Cardiovascular Research Institute, University of California-San Francisco, 555 South Mission Bay Blvd, San Francisco, CA, 94158, USA
- Department of Physiology, University of California-San Francisco, 555 South Mission Bay Blvd, San Francisco, CA, 94158, USA
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Wu L, Wu D, Yang T, Xu J, Chen J, Wang L, Xu S, Zhao W, Wu C, Ji X. Hypothermic neuroprotection against acute ischemic stroke: The 2019 update. J Cereb Blood Flow Metab 2020; 40:461-481. [PMID: 31856639 PMCID: PMC7026854 DOI: 10.1177/0271678x19894869] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 11/14/2019] [Accepted: 11/18/2019] [Indexed: 02/06/2023]
Abstract
Acute ischemic stroke is a leading cause of death and disability worldwide. Therapeutic hypothermia has long been considered as one of the most robust neuroprotective strategies. Although the neuroprotective effects of hypothermia have only been confirmed in patients with global cerebral ischemia after cardiac arrest and in neonatal hypoxic ischemic encephalopathy, establishing standardized protocols and strictly controlling the key parameters may extend its application in other brain injuries, such as acute ischemic stroke. In this review, we discuss the potential neuroprotective effects of hypothermia, its drawbacks evidenced in previous studies, and its potential clinical application for acute ischemic stroke especially in the era of reperfusion. Based on the different conditions between bench and bedside settings, we demonstrate the importance of vascular recanalization for neuroprotection of hypothermia by analyzing numerous literatures regarding hypothermia in focal cerebral ischemia. Then, we make a thorough analysis of key parameters of hypothermia and introduce novel hypothermic therapies. We advocate in favor of the process of clinical translation of intra-arterial selective cooling infusion in the era of reperfusion and provide insights into the prospects of hypothermia in acute ischemic stroke.
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Affiliation(s)
- Longfei Wu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Di Wu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Tuo Yang
- Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jin Xu
- Department of Library, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jian Chen
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Luling Wang
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Shuaili Xu
- Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Wenbo Zhao
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Chuanjie Wu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xunming Ji
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
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Whole body hypothermia extends tissue plasminogen activator treatment window in the rat model of embolic stroke. Life Sci 2020; 256:117450. [PMID: 32087233 DOI: 10.1016/j.lfs.2020.117450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 02/13/2020] [Accepted: 02/19/2020] [Indexed: 12/12/2022]
Abstract
Late treatment with tissue plasminogen activator (tPA) leads to reperfusion injury and poor outcome in ischemic stroke. We have recently shown the beneficial effects of local brain hypothermia after late thrombolysis. Herein, we investigated whether transient whole-body hypothermia was neuroprotective and could prevent the side effects of late tPA therapy at 5.5 h after embolic stroke. After induction of stroke, male rats were randomly assigned into four groups: Control, Hypothermia, tPA and Hypothermia+tPA. Hypothermia started at 5 h after embolic stroke and continued for 1 h. Thirty min after hypothermia, tPA was administrated. Infarct volume, brain edema, blood-brain barrier (BBB) and matrix metalloproteinase-9 (MMP-9) were assessed 48 h and neurological functions were assessed 24 and 48 hour post-stroke. Compared with the control or tPA groups, whole-body hypothermia decreased infarct volume (P < 0.01), BBB disruption (P < 0.05) and MMP-9 level (P < 0.05). However, compared with hypothermia alone a combination of hypothermia and tPA was more effective in reducing infarct volume. While hypothermia alone did not show any effect, its combination with tPA reduced brain edema (P < 0.05). Hypothermia alone or when combined with tPA decreased MMP-9 compared with control or tPA groups (P < 0.01). Although delayed tPA therapy exacerbated BBB integrity, general cooling hampered its leakage after late thrombolysis (P < 0.05). Moreover, only combination therapy significantly improved sensorimotor function as well as forelimb muscle strength at 24 or 48 h after stroke (P < 0.01). Transient whole-body hypothermia in combination with delayed thrombolysis therapy shows more neuroprotection and extends therapeutic time window of tPA up to 5.5 h.
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Katica-Mulalic A, Suljic E, Begic E, Mukanovic-Alihodzic A, Straus S, Feto A, Dedovic Z, Gojak R. Effect of Therapeutic Hypothermia on Liver Enzymes in Patients With Stroke. Med Arch 2020; 74:470-473. [PMID: 33603273 PMCID: PMC7879342 DOI: 10.5455/medarh.2020.74.470-473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Introduction: A promising strategy that can lead to longer brain cell survival after an acute stroke is therapeutic hypothermia. It represents a controlled decrease in body temperature for therapeutic reasons. It is increasingly represented as a therapeutic option and is one of the most challenging treatments that improves neurological recovery and treatment outcome in patients with acute stroke. Aim: To examine the effect of therapeutic hypothermia on liver enzymes in patients with diagnosis of stroke. Methods: A total of 101 patients diagnosed with acute stroke were treated. The first group (n=40) were treated with conventional treatment and therapeutic hypothermia, while the second group (n=61) only with conventional treatment. Cooling of the body to a target body temperature of 34°C to 35°C was performed for up to 24 hours. Outcome (survival or death) of treatment was monitored, degree of disability was determined by National Institutes of Health Stroke Scale (NIHSS) and assessment of consciousness using the Glasgow Coma Scale (GCS). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were taken at admission, after 24 hours, and were monitored upon discharge. Results: There was a significant difference in AST values at admission relative to disease outcome (p = 0.002), as well as for ALT (p = 0.008). In patients treated with therapeutic hypothermia, mean AST values decreased after 24 hours (32.50 to 31.00 IU/mL) as well as ALT values (27.50 to 26.50 IU/mL), without statistical significance. In the group of subjects who survived with sequela, AST values correlated with GCS (rho = -0.489; p = 0.002) and NIHSS (rho = 0.492; p = 0.003), ALT values correlated with GCS (rho = -0.356; p = 0.03) but not with NIHSS. Conclusion: AST and ALT values at admission correlate with the severity of the clinical picture. Therapeutic hypothermia is hepatoprotective and lowers AST and ALT values.
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Affiliation(s)
- Amela Katica-Mulalic
- Clinic Anesthesiology and Resuscitation, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Enra Suljic
- Department for Science, Teaching and Clinical Trials, Clinical Centre University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Edin Begic
- Department of Cardiology, General Hospital «Prim. dr. Abdulah Nakas», Sarajevo, Bosnia and Herzegovina
| | - Azra Mukanovic-Alihodzic
- Clinic Anesthesiology and Resuscitation, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Slavenka Straus
- Clinic for Cardiovascular Surgery, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Amila Feto
- Clinic Anesthesiology and Resuscitation, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Zenaida Dedovic
- Clinic Anesthesiology and Resuscitation, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Refet Gojak
- Clinic for Infectious Diseases, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
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Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344-e418. [PMID: 31662037 DOI: 10.1161/str.0000000000000211] [Citation(s) in RCA: 4038] [Impact Index Per Article: 673.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.
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Bertalan G, Boehm-Sturm P, Schreyer S, Morr AS, Steiner B, Tzschätzsch H, Braun J, Guo J, Sack I. The influence of body temperature on tissue stiffness, blood perfusion, and water diffusion in the mouse brain. Acta Biomater 2019; 96:412-420. [PMID: 31247381 DOI: 10.1016/j.actbio.2019.06.034] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 05/28/2019] [Accepted: 06/20/2019] [Indexed: 12/11/2022]
Abstract
While hypothermia of the brain is used to reduce neuronal damage in patients with conditions such as traumatic brain injury or stroke, little is known about how temperature affects the biophysical properties of in vivo brain tissue. Therefore, we measured shear wave speed (SWS), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) in the mouse brain at different body temperatures to investigate the relationship between temperature and tissue stiffness, water diffusion, and blood perfusion in the living brain. Multifrequency magnetic resonance elastography (MRE), diffusion-weighted imaging (DWI), and arterial spin labeling (ASL) were performed in seven mice while increasing and recording body temperature from hypothermia (28-30 °C) to normothermia (36-38 °C). SWS, ADC, and CBF were analyzed in regions of whole brain, cortex, hippocampus, and diencephalon. Our results show that SWS decreases while ADC and CBF increase from hypothermia to normothermia (whole brain SWS: -6.2%, ADC: +34.0%, CBF: +80.2%; cortex SWS: -10.1%, ADC: +30.9%, CBF: +82.4%; all p > 0.05). We found a significant inverse correlation between SWS and both ADC and CBF in all analyzed regions except diencephalon (whole brain SWS-ADC: r = -0.8, p < 0.005; SWS-CBF: r = -0.84, p < 0.005; cortex SWS-ADC: r = -0.74, p < 0.05; SWS-CBF: r = -0.65, p < 0.05). These results show that in vivo brain stiffness is inversely correlated with temperature, extracellular water mobility, and microvascular blood flow. Regional differences indicate that cortical areas are more markedly affected by hypothermia than central regions such as diencephalon. Temperature should be considered as a confounder in elastographic measurements, especially in preclinical settings. STATEMENT OF SIGNIFICANCE: Hibernating mammals lower their body temperature and metabolic activity. A hypothermic state can also be induced for medical purposes to reduce the risk of neural damage in patients with neurological disease or injury. However, little is known how physical soft-tissue properties of the in-vivo brain such as water diffusion, blood perfusion or mechanical parameters correlate with each other when temperature changes. Our study demonstrates for the first time that those quantitative imaging markers are tightly linked to changes in body temperature. While water diffusion and blood perfusion are reduced during hypothermia, brain stiffness significantly increases, suggesting that multiparametric quantitative MRI should be used for the noninvasive assessment of brain metabolic activity.
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Baron JC. Protecting the ischaemic penumbra as an adjunct to thrombectomy for acute stroke. Nat Rev Neurol 2019; 14:325-337. [PMID: 29674752 DOI: 10.1038/s41582-018-0002-2] [Citation(s) in RCA: 127] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
After ischaemic stroke, brain damage can be curtailed by rescuing the 'ischaemic penumbra' - that is, the severely hypoperfused, at-risk but not yet infarcted tissue. Current evidence-based treatments involve restoration of blood flow so as to salvage the penumbra before it evolves into irreversibly damaged tissue, termed the 'core'. Intravenous thrombolysis (IVT) can salvage the penumbra if given within 4.5 h after stroke onset; however, the early recanalization rate is only ~30%. Direct removal of the occluding clot by mechanical thrombectomy considerably improves outcomes over IVT alone, but despite early recanalization in > 80% of cases, ~50% of patients who receive this treatment do not enjoy functional independence, usually because the core is already too large at the time of recanalization. Novel therapies aiming to 'freeze' the penumbra - that is, prevent core growth until recanalization is complete - hold potential as adjuncts to mechanical thrombectomy. This Review focuses on nonpharmacological approaches that aim to restore the physiological balance between oxygen delivery to and oxygen demand of the penumbra. Particular emphasis is placed on normobaric oxygen therapy, hypothermia and sensory stimulation. Preclinical evidence and early pilot clinical trials are critically reviewed, and future directions, including clinical translation and trial design issues, are discussed.
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Affiliation(s)
- Jean-Claude Baron
- Department of Neurology, Hôpital Sainte-Anne, Université Paris 5, INSERM U894, Paris, France.
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