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Gutkovich YE, Jamison A, Lagami D, Fonar Y, Siag K, Tal D. Video head impulse test and seasickness susceptibility. Exp Brain Res 2025; 243:119. [PMID: 40237844 DOI: 10.1007/s00221-025-07078-9] [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: 09/10/2024] [Accepted: 04/03/2025] [Indexed: 04/18/2025]
Abstract
Seasickness can have a devastating effect on a crewmember's well-being. In the literature, there is a controversy about whether car sickness could be diagnosed by vestibular evaluation tests, specifically by Video Head impulse test (vHIT) a semi-circular canal (SCC) function test. These consequences might be relevant to seasickness susceptibility. Angular acceleration at the pitch and roll planes lead to the development of seasickness. Normative data from vHIT indicates that the vestibulo-ocular reflex (VOR) gain for the anterior and posterior semicircular canals is lower and more variable compared to the lateral SCC VOR gain. It is expected that these differences will be evident in vHIT testing between individuals who are susceptible to seasickness and those who are not. Eighty-six maritime military personnel were assigned to the study. Participants were classified as non-susceptible based on Golding (1-3) and Motion sickness score ≥ 8. Seasickness-susceptible subjects were classified as Golding 6 and Motion sickness score ≤ 7. There was no significant difference in vertical VOR gains, asymmetry ratios, or the proportion of individuals with corrective saccades between the study groups. The results could not differentiate between study groups by the standard vHIT parameters. Further analysis of the left ipsilateral anterior to lateral vHIT mean VOR gain ratio has revealed a significantly lower ratio for the seasickness susceptible group (0.896 ± 0.126 and 0.963 ± 0.128 in seasickness susceptible and non-susceptible groups, respectively, Student's unpaired t-test, P = 0.0187; Cohen's d effect size 0.527543). This observation should be considered as an additional vHIT parameter when evaluating susceptibility to seasickness. This study was retrospectively registered on December 11th, 2022 and assigned the identifier number NCT05657340.
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Affiliation(s)
- Yoni Evgeni Gutkovich
- Motion Sickness and Human Performance Laboratory, The Israel Naval Medical Institute, IDF Medical Corps, Haifa, Israel
- Department of Otolaryngology, Head and Neck Surgery, Emek Medical Center, Afula, Israel
| | - Anna Jamison
- Motion Sickness and Human Performance Laboratory, The Israel Naval Medical Institute, IDF Medical Corps, Haifa, Israel
| | - Daniel Lagami
- Motion Sickness and Human Performance Laboratory, The Israel Naval Medical Institute, IDF Medical Corps, Haifa, Israel
| | - Yuri Fonar
- Motion Sickness and Human Performance Laboratory, The Israel Naval Medical Institute, IDF Medical Corps, Haifa, Israel
- Shalvata Mental Health Center, HodHasharon, Israel
| | - Kfir Siag
- Department of Otolaryngology, Head and Neck Surgery, Emek Medical Center, Afula, Israel
| | - Dror Tal
- Motion Sickness and Human Performance Laboratory, The Israel Naval Medical Institute, IDF Medical Corps, Haifa, Israel.
- Motion Sickness and Human Performance Laboratory, The Israel Naval Medical Institute (INMI), Box 22 Rambam Health Care Campus, P.O. Box 9602, Haifa, 3109601, Israel.
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Aoki N, Yamazaki A, Honda K, Tsutsumi T. Ocular torsion induced by Coriolis stimulation. Auris Nasus Larynx 2024; 51:738-746. [PMID: 38850719 DOI: 10.1016/j.anl.2024.05.011] [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: 12/03/2023] [Revised: 05/23/2024] [Accepted: 05/28/2024] [Indexed: 06/10/2024]
Abstract
OBJECTIVE The present study aimed to observe and analyze the ocular movements induced by Coriolis stimulation (eccentric pitch while rotating: PWR) that induces Coriolis forces on the vestibular apparatus of healthy human individuals. METHODS A total of 31 healthy subjects participated in the study. Eccentric PWR was performed on 27 subjects, by pitching the participants' heads forward and backward at an angle of 30° each on an axis parallel and 7 cm below inter-aural axis, at a frequency of 0.5 Hz while on a chair rotating at a constant angular velocity of 97.2°/s on the earth-vertical axis. Ocular movements during stimulation were recorded using three-dimensional video-oculography. As a subsidiary analysis, 0.5 Hz head roll tilt was used as another stimulus that also induced torsional ocular movements. The forces induced on the vestibular apparatus, and phases of ocular torsion against the stimulus were calculated from the observed data. RESULTS In the Coriolis stimulation during rightward yaw rotation, a rightward ocular torsion of 4.8° on average, was observed when the head pitched forward, and the direction of ocular torsion reversed when the head pitched backward. During leftward yaw rotation, these relationships were reversed with an average amplitude of 4.7° The phase of ocular torsion preceded that of Coriolis force by 0.2 s during rightward rotation and 0.14 s during leftward rotation. There were no significant differences in amplitude or phase between the directions of rotation. The phase lead of 0.5 Hz roll-tilt was significantly smaller than that of Coriolis stimulation (p < 0.01). CONCLUSION Coriolis stimulation induced a specific pattern of ocular torsion, where its direction and phase suggested that the mechanism likely involved both the otolith and semicircular canals. Further studies may provide a clue to the magnitude of the otolith and semicircular canal contributions.
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Affiliation(s)
- Natsuki Aoki
- Department of Otolaryngology, Tokyo Medical and Dental university, Tokyo, Japan
| | - Ayame Yamazaki
- Department of Otolaryngology, Tokyo Medical and Dental university, Tokyo, Japan
| | - Keiji Honda
- Department of Otolaryngology, Tokyo Medical and Dental university, Tokyo, Japan
| | - Takeshi Tsutsumi
- Department of Otolaryngology, Tokyo Medical and Dental university, Tokyo, Japan.
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Rahman SM, Buchholz DW, Imbiakha B, Jager MC, Leach J, Osborn RM, Birmingham AO, Dewhurst S, Aguilar HC, Luebke AE. Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs. J Virol 2024; 98:e0006624. [PMID: 38814068 PMCID: PMC11265435 DOI: 10.1128/jvi.00066-24] [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: 01/10/2024] [Accepted: 04/15/2024] [Indexed: 05/31/2024] Open
Abstract
COVID-19 can cause neurological symptoms such as fever, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have been hardly assessed in mouse models. In this study, we infected two commonly used wild-type mouse lines (C57BL/6J and 129/SvEv) and a 129S calcitonin gene-related peptide (αCGRP) null-line with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including fever, dizziness, and nausea. We then evaluated whether a CGRP receptor antagonist, olcegepant, a "gepant" antagonist used in migraine treatment, could mitigate acute neuroinflammatory and neurological signs of SARS-COV-2 infection. First, we determined whether CGRP receptor antagonism provided protection from permanent weight loss in older (>18 m) C57BL/6J and 129/SvEv mice. We also observed acute fever, dizziness, and nausea in all older mice, regardless of treatment. In both wild-type mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP receptor signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic or endemic coronavirus outbreaks.IMPORTANCECoronavirus disease (COVID-19) can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of severe acute respiratory syndrome CoV-2 (SARS-CoV-2) infection have been hardly assessed in mouse models. In this study, we first infected two commonly used wild-type mouse lines (C57BL/6J and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological symptoms including fever and nausea. Furthermore, we showed that the migraine treatment drug olcegepant could reduce long-term weight loss and IL-6 release associated with SARS-CoV-2 infection. These findings suggest that a migraine blocker can be protective for at least some acute SARS-CoV-2 infection signs and raise the possibility that it may also impact long-term outcomes.
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Affiliation(s)
- Shafaqat M. Rahman
- Departments of Biomedical Engineering, Neuroscience, Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA
| | - David W. Buchholz
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Brian Imbiakha
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Mason C. Jager
- Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Justin Leach
- Departments of Biomedical Engineering, Neuroscience, Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA
| | - Raven M. Osborn
- Departments of Biomedical Engineering, Neuroscience, Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA
| | - Ann O. Birmingham
- Departments of Biomedical Engineering, Neuroscience, Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA
| | - Stephen Dewhurst
- Departments of Biomedical Engineering, Neuroscience, Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA
| | - Hector C. Aguilar
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Anne E. Luebke
- Departments of Biomedical Engineering, Neuroscience, Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA
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Bawa Z, McCartney D, Bedoya-Pérez M, Lau NS, Fox R, MacDougall H, McGregor IS. Effects of cannabidiol on psychosocial stress, situational anxiety and nausea in a virtual reality environment: a protocol for a single-centre randomised clinical trial. BMJ Open 2024; 14:e082927. [PMID: 38531572 PMCID: PMC10966725 DOI: 10.1136/bmjopen-2023-082927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 03/13/2024] [Indexed: 03/28/2024] Open
Abstract
INTRODUCTION The non-intoxicating plant-derived cannabinoid, cannabidiol (CBD), has demonstrated therapeutic potential in a number of clinical conditions. Most successful clinical trials have used relatively high (≥300 mg) oral doses of CBD. Relatively few studies have investigated the efficacy of lower (<300 mg) oral doses, typical of those available in over-the-counter CBD products. METHODS We present a protocol for a randomised, double-blind, placebo-controlled, parallel-group clinical trial investigating the effects of a low oral dose (150 mg) of CBD on acute psychosocial stress, situational anxiety, motion sickness and cybersickness in healthy individuals. Participants (n=74) will receive 150 mg of CBD or a matched placebo 90 min before completing three virtual reality (VR) challenges (tasks) designed to induce transient stress and motion sickness: (a) a 15 min 'Public Speaking' task; (b) a 5 min 'Walk the Plank' task (above a sheer drop); and (c) a 5 min 'Rollercoaster Ride' task. The primary outcomes will be self-reported stress and nausea measured on 100 mm Visual Analogue Scales. Secondary outcomes will include salivary cortisol concentrations, skin conductance, heart rate and vomiting episodes (if any). Statistical analyses will test the hypothesis that CBD reduces nausea and attenuates subjective, endocrine and physiological responses to stress compared with placebo. This study will indicate whether low-dose oral CBD has positive effects in reducing acute psychosocial stress, situational anxiety, motion sickness and cybersickness. ETHICS AND DISSEMINATION The University of Sydney Human Research Ethics Committee has granted approval (2023/307, version 1.6, 16 February 2024). Study findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER Australian New Zealand Clinical Trials Registry (ACTRN12623000872639).
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Affiliation(s)
- Zeeta Bawa
- The Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia
- The Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
- Sydney Pharmacy School, The University of Sydney, Sydney, New South Wales, Australia
| | - Danielle McCartney
- The Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia
- The Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
- School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
| | - Miguel Bedoya-Pérez
- The Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia
- The Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
- School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
| | - Namson S Lau
- The Boden Initiative, Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Richard Fox
- Yellow Dog Man Studios s.r.o, Ostrava-jih-Zábřeh, Czechia
| | - Hamish MacDougall
- RPA Institute of Academic Surgery, Sydney Local Health District, Sydney, New South Wales, Australia
| | - Iain S McGregor
- The Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia
- The Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
- School of Psychology, The University of Sydney, Sydney, New South Wales, Australia
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Rahman SM, Buchholz DW, Imbiakha B, Jaeger MC, Leach J, Osborn RM, Birmingham AO, Dewhurst S, Aguilar HC, Luebke AE. Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.10.23.563669. [PMID: 37965203 PMCID: PMC10634772 DOI: 10.1101/2023.10.23.563669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2023]
Abstract
COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion-related dizziness. We then evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 αCGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. First, we determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic and/or endemic coronaviruses.
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Zhou L, Hu H, Qin B, Zhu Q, Qian Z. Brain activity differences between susceptible and non-susceptible populations under visually induced motion sickness based on sensor-space and source-space analyses. Brain Res 2023; 1815:148474. [PMID: 37393010 DOI: 10.1016/j.brainres.2023.148474] [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: 02/18/2023] [Revised: 06/25/2023] [Accepted: 06/28/2023] [Indexed: 07/03/2023]
Abstract
The neural mechanisms underlying visually induced motion sickness (VIMS) in different susceptible populations are unclear, as it is not clear how brain activity changes in different susceptible populations during the vection section (VS). This study aimed to analyze the brain activity changes in different susceptible populations during VS. Twenty subjects were included in this study and divided into the VIMS-susceptible group (VIMSSG) and VIMS-resistant group (VIMSRG) based on a motion sickness questionnaire. 64-channel electroencephalogram (EEG) data from these subjects during VS were collected. The brain activities during VS for VIMSSG and VIMSRG were analyzed with time-frequency based sensor-space analysis and EEG source imaging based source-space analysis. Under VS, delta and theta energies were significantly increased in VIMSSG and VIMSRG, while alpha and beta energies were only significantly increased in VIMSRG. Also, the superior and middle temporal were activated in VIMSSG and VIMSRG, while lateral occipital, supramarginal gyrus, and precentral gyrus were activated only in VIMSSG. The spatiotemporal differences in brain activity observed between VIMSSG and VIMSRG may be attributed to the different susceptibility of participants in each group and the different severity of MS symptoms experienced. Long-term vestibular training can effectively improve the ability of anti-VIMS. The knowledge gained from this study helps advance understanding of the neural mechanism of VIMS in different susceptible populations.
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Affiliation(s)
- Lu Zhou
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, China; Key Laboratory of Multimodal Brain-Computer Precision Drive Ministry of Industry and Information Technology, Nanjing, 210016, China; Key Laboratory of Digital Medical Equipment and Technology of Jiangsu Province, Nanjing, 210016, China
| | - Haixu Hu
- Sports Training Academy, Nanjing Sport Institute, Nanjing, 210016, China
| | - Bing Qin
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, China; Key Laboratory of Multimodal Brain-Computer Precision Drive Ministry of Industry and Information Technology, Nanjing, 210016, China; Key Laboratory of Digital Medical Equipment and Technology of Jiangsu Province, Nanjing, 210016, China
| | - Qiaoqiao Zhu
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, China; Key Laboratory of Multimodal Brain-Computer Precision Drive Ministry of Industry and Information Technology, Nanjing, 210016, China; Key Laboratory of Digital Medical Equipment and Technology of Jiangsu Province, Nanjing, 210016, China.
| | - Zhiyu Qian
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, China; Key Laboratory of Multimodal Brain-Computer Precision Drive Ministry of Industry and Information Technology, Nanjing, 210016, China; Key Laboratory of Digital Medical Equipment and Technology of Jiangsu Province, Nanjing, 210016, China.
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Zhang ZH, Liu LP, Fang Y, Wang XC, Wang W, Chan YS, Wang L, Li H, Li YQ, Zhang FX. A New Vestibular Stimulation Mode for Motion Sickness With Emphatic Analysis of Pica. Front Behav Neurosci 2022; 16:882695. [PMID: 35600993 PMCID: PMC9115577 DOI: 10.3389/fnbeh.2022.882695] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 03/30/2022] [Indexed: 11/13/2022] Open
Abstract
Motion sickness (MS) was frequently introduced for rodents in research work through passive motion that disturbed vestibular signals in the presence of visual and aleatory, proprioceptive inputs. Inducement of MS in this way causes conflicting signals that activate intermixed neural circuits representing multimodal stimulation. From reductionism, a lab setup to elicit rat MS via vestibular stimulation was configured in the present study for MS study in connection with dissection of the central vestibular component causally underlying MS. The individual animal was blinded to light with a custom-made restrainer, and positioned at an inclination of 30° for otolith organs to receive unusual actions by gravitoinertial vector. Following a 2-h double-axis (earth-vertical) rotation involving angular acceleration/deceleration, a suit of behaviors characterizing the MS was observed to be significantly changed including pica (eating non-nutritive substance like kaolin), conditioned taste avoidance and locomotion (p < 0.05). Notably, for the statistical hypothesis testing, the utility of net increased amount of kaolin consumption as independent variables in data processing was expounded. In addition, Fos-immunostained neurons in vestibular nucleus complex were significantly increased in number, suggesting the rotation-induced MS was closely related to the vestibular activation. In conclusion, our work indicated that the present setup could effectively elicit the MS by disturbing vestibular signals in rat in the context of well-controlled proprioceptive inputs and lack of visual afference.
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Affiliation(s)
- Zhi-Hao Zhang
- Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
- Department of Anatomy, Medical College, Yan’an University, Yan’an, China
| | - Li-Peng Liu
- Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Yan Fang
- Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Xiao-Cheng Wang
- Center of Clinical Aerospace Medicine, School of Aerospace Medicine, Fourth Military Medical University, Xi’an, China
| | - Wei Wang
- Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
- Department of Pharmacology, Xi’an Biomedicine College, Xi’an, China
| | - Ying-Shing Chan
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Lu Wang
- Department of Anatomy, Medical College, Yan’an University, Yan’an, China
| | - Hui Li
- Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Yun-Qing Li
- Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Fu-Xing Zhang
- Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, School of Basic Medicine, Fourth Military Medical University, Xi’an, China
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Zhu HS, Li D, Li C, Huang JX, Chen SS, Li LB, Shi Q, Ju XL. Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion. World J Stem Cells 2021; 13:177-192. [PMID: 33708346 PMCID: PMC7933988 DOI: 10.4252/wjsc.v13.i2.177] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 10/31/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Motion sickness (MS) is a disease that occurs during unbalanced movement, characterized by gastrointestinal symptoms and autonomic nervous system activation. Current clinical treatments for MS are limited. Recent evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune imbalance. In the present study, mesenchymal stem cells (MSCs) have been shown to exert strong immuno-suppressive effects.
AIM To explore whether umbilical cord-derived mesenchymal stem cells (UC-MSCs) can prevent the occurrence of MS, and the underlying mechanism regulated by MSCs in a mouse model of MS.
METHODS A total of 144 (equal numbers of males and females) 5wkold BALB/c mice were randomly divided into five groups: Normal group (n = 16), MS group (n = 32), MSCs group (n = 32), MS + MSCs group (n = 32), and MS + AS101/MSCs group (n = 32). The MSCs group (n = 32), MS + MSCs group (n = 32), and MS + AS101/MSCs group (n = 32) were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs (1 × 106 cells/mouse). Mice in the MS (n = 32), MS + MSCs, and MS + AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8 × g/min for MS model establishment on days 3, 5, 8, and 10 after UC-MSCs injection. The Morris water maze (MWM) test was used to observe the symptom of dizziness. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone samples. Western blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear tissues. Histological examination was performed by hematoxylin and eosin (HE) staining for conventional morphological evaluation in the petrous part of temporal bone samples.
RESULTS The MWM test demonstrated that UC-MSCs improved the symptoms of MS. The MS + MSCs group was faster than the MS group on days 3 and 5 (P = 0.036 and P = 0.002, respectively). ELISA and RT-qPCR showed that the serum and mRNA levels of interleukin-10 (IL-10) in the cochlear tissues were increased after transplantation with UC-MSCs (MS + MSCs group vs MS group at 3 and 5 d, P = 0.002 and cP < 0.001, respectively). RT-qPCR results confirmed a significant increase in IL-10 levels at four time points (MS + MSCs group vs MS group, P = 0.009, P = 0.009, P = 0.048, and P = 0.049, respectively). This suggested that UC-MSCs reduced the sensitivity of the vestibular microenvironment by secreting IL-10. Moreover, Western blot analysis showed that the MSCs activated the JAK2/STAT3 signaling pathway in the cochlear tissues. The levels of IL-10, IL-10RA, JAK2, STAT3, and phosphorylated JAK2 and STAT3 in the MS + MSCs group were increased compared to those of the MS group (P < 0.05). The morphological changes in the four groups showed no significant differences. The role of IL-10 secretion on the ability of UC-MSCs to successfully improve the symptoms of MS was confirmed by the diminished therapeutic effects associated with treatment with the IL-10 inhibitor ammonium trichloro (dioxoethylene-o,o′) tellurate (AS101).
CONCLUSION Prophylactic transplantation of UC-MSCs can alleviate the clinical symptoms of MS in mice, particularly at 3-5 d after preventive transplantation. The mechanism for UC-MSCs to reduce the sensitivity of vestibular cortex imbalance may be the secretion of IL-10. The next step is to demonstrate the possibility of curing MS in the vestibular environment by intermittent transplantation of MSCs. Above all, MSCs are expected to become a new method for the clinical prevention and treatment of MS.
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Affiliation(s)
- Hua-Su Zhu
- Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Dong Li
- Stem Cell and Regenerative Medicine Research Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Cong Li
- Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Jin-Xian Huang
- Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Shan-Shan Chen
- Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Lan-Bo Li
- Department of Animal Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Qing Shi
- Stem Cell and Regenerative Medicine Research Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Xiu-Li Ju
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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Aghababaei Ziarati M, Taziki MH, Hosseini SM. Autonomic laterality in caloric vestibular stimulation. World J Cardiol 2020; 12:144-154. [PMID: 32431785 PMCID: PMC7215963 DOI: 10.4330/wjc.v12.i4.144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 03/12/2020] [Accepted: 03/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Caloric stimulation of the vestibular system is associated with autonomic response. The lateralization in the nervous system activities also involves the autonomic nervous system.
AIM To compare the effect of the right and left ear caloric test on the cardiac sympathovagal tone in healthy persons.
METHODS This self-control study was conducted on 12 healthy male volunteers. The minimal ice water caloric test was applied for vestibular stimulation. This was done by irrigating 1 milliliter of 4 ± 2 °C ice water into the external ear canal in 1 s. In each experiment, only one ear was stimulated. For each ear, the pessimum position was considered as sham control and the optimum position was set as caloric vestibular stimulation of horizontal semicircular channel. The order of right or left caloric vestibular stimulation and the sequence of optimum or pessimum head position in each set were random. The recovery time between each calorie test was 5 min. The short-term heart rate variability (HRV) was used for cardiac sympathovagal tone metrics. All variables were compared using the analysis of variance.
RESULTS After caloric vestibular stimulation, the short-term time-domain and frequency-domain HRV indices as well as, the systolic and the diastolic arterial blood pressure, the respiratory rate and the respiratory amplitude, had no significant changes. These negative results were similar in the right and the left sides. Nystagmus duration of left caloric vestibular stimulations in the optimum and the pessimum positions had significant differences (e.g., 72.14 ± 39.06 vs 45.35 ± 35.65, P < 0.01). Nystagmus duration of right caloric vestibular stimulations in the optimum and the pessimum positions had also significant differences (e.g., 86.42 ± 67.20 vs 50.71 ± 29.73, P < 0.01). The time of the start of the nystagmus following caloric vestibular stimulation had no differences in both sides and both positions.
CONCLUSION Minimal ice water caloric stimulation of the right and left vestibular system did not affect the cardiac sympathovagal balance according to HRV indices.
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Affiliation(s)
- Mohammadreza Aghababaei Ziarati
- Department of Internal Medicine, Medical Faculty, Golestan University of Medical Sciences, Gorgan 4934174515, Golestan, Iran
| | - Mohammad Hosein Taziki
- Department of Otolaryngology, Medical Faculty, Golestan University of Medical Sciences, Gorgan 4934174515, Golestan, Iran
| | - Seyed Mehran Hosseini
- Department of Physiology, Medical Faculty, Golestan University of Medical Sciences, Gorgan 4934174515, Golestan, Iran
- Neuroscience Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan 4934174515, Golestan, Iran
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