Traumatic brain injury (TBI) is an acquired neurological insult that has become a major cause of mortality.Hence, immediate and appropriate medical attention is essential. The present study investigated the neuroprotective effect of 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid against a weight drop model of traumatic brain injury (TBI). During the in-vitro analysis, ECN demonstrated neuroprotective potential by remarkably improving the cell viability and also provided significant protection in case of nitric oxide-evoked oxidative stress in HT22 cells. The administration of ECN significantly improved the neurological severity score, and mechanical/periorbital allodynia following TBI, when compared with the TBI-group. The level of brain edema and blood-brain barrier (BBB) disruption were also significantly reduced by ECN treatment. ECN also restored constitutional changes in the protein/lipid profile; simultaneous with histological changes in the brain in contrast to the TBI-group. It significantly ameliorated neuronal loss and also minimized the intracerebral hemorrhages arising from traumatic insult. ECN exhibited potent anti-inflammatory effects, by altering the expression of extracellular-signal-regulated kinase (ERK), p38, and activating protein-1 (AP-1) proteins. It also exhibited antioxidant effects by increasing the production levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Furthermore, ECN also produced an anti-apoptotic effect by downregulation of caspase3 and upregulation of B-cell lymphoma 2 (Bcl-2). It also increased the levels of antioxidants while reducing the levels of oxidative stress and inflammatory markers in comparison to the TBI-group. In short, it was concluded that ECN exhibited protective anti-inflammatory, antioxidant, and anti-apoptotic effects against trauma-induced brain injury.

Mild traumatic brain injury (mTBI), often resulting from traffic accidents, workplace incidents, sports, or recreational activities, is a neurological condition that significantly impacts the daily lives of many individuals. The absence of reliable biomarkers and the non-specific nature of mTBI symptoms pose challenges for accurate diagnosis, leading to undetected cases and potential long-term consequences. Current diagnostic approaches, including neuroimaging, serum biomarkers, and cognitive assessments, suffer from cost, invasiveness, and sensitivity limitations. To address this, we developed a novel electrochemical detection platform for salivary microRNAs (miRNAs), offering a rapid, non-invasive, and cost-effective alternative for mTBI diagnosis. Key challenges in point-of-care miRNA detection lie in low abundance, short length, sequence complementarity, degradation, and amplification-free detection with high sensitivity and specificity. This platform technology introduces a de novo-synthesized, conductive carboxyl-functionalized thiophene polymer (AAOT:PSS)-coated gold electrode, enabling the covalent attachment of streptavidin-linked, biotinylated anti-miRNAs with methylene blue as the electrochemical reporter. This system successfully detected picomolar concentrations of mTBI-associated miRNAs (miR-let7a, miR-30e, miR-21) in saliva, outperforming traditional methods and establishing salivary miRNAs as highly reliable biomarkers for mTBI. Our approach leverages the mTBI-induced upregulation of miR-let7a, miR-30e, miR-21 as proof-of-concept targets with scope of multiplexing while achieving 100% sensitivity and specificity in patient-derived samples validated via PCR and clinical assessments.

Previous guidance for mild concussion treatment has recommended physical and cognitive rest. However, it remains unknown if patients who received treatment at different times had differential neuropsychiatric outcomes. We examined if patients who received immediate treatment less than one week after a mild concussion had a different risk for subsequent depression or anxiety compared with those who received delayed treatment greater than one week after the event, stratified by age groups. This multicenter retrospective cohort study used the TriNetX Analytics platform to access de-identified electronic health records of over 100 million patients, including both inpatient and outpatient visits, from 60 healthcare organizations across the United States. A total of 9881 patients with a diagnosis of mild concussion either received either immediate treatment, defined as within 1 week (n = 4053), or delayed treatment, defined as 1 week to 6 months (n = 5828) following the diagnosis of mild concussion. Each group was stratified by age:≤25, 26-64, and 65+ years. Patients who received early treatment had significantly lower risk of depression and anxiety compared with propensity-score matched patients who received delayed treatment during a 5-year follow-up after mild TBI diagnosis, with hazard ratios (HRs) of 0.74 (95 % CI, 0.65-0.84) and 0.75 (95 % CI, 0.68-0.84), respectively. These results are consistent across age groups, with strongest reduction in older adults aged 65 years and older. These findings suggest that timely treatment for concussion may mitigate subsequent adverse psychiatric outcomes.

Veterans experience a high prevalence of traumatic brain injuries (TBIs) due to combat-related incidents such as explosive blasts, penetrating injuries, and blunt force trauma. These military TBIs are often more complex than civilian TBIs, leading to increased long-term neurological consequences. Over 414,000 service members have been diagnosed with TBI since 2000, highlighting the need to understand the implications of these injuries and the neurosurgical challenges in their treatment.

This narrative review examines the literature on TBIs in veterans, focusing on the characteristics, health impacts, and neurosurgical challenges associated with these injuries. The review synthesizes relevant articles to provide an overview of the topic.

Veterans with TBIs commonly experience cognitive deficits, including impairments in memory, executive functioning, processing speed, and visual disturbances. Research explores the relationship between TBI and neurodegenerative diseases, with some studies indicating a correlation between TBI severity and an increased risk of all-cause and vascular dementia. Managing TBIs in veterans presents neurosurgical challenges such as timely diagnosis and intervention, tailored treatment approaches due to injury variability (blast vs. blunt trauma), and co-occurring conditions like PTSD and depression. Initial medical measures include osmotherapy, sedation, hyperventilation, oxygenation, control of temperature and infection. In specific scenarios, an external ventricular drain (EVD) may be necessary to drain cerebrospinal fluid (CSF).

Addressing TBIs in veterans necessitates a multidisciplinary approach with timely neurosurgical interventions, comprehensive rehabilitation, and mental health support. Future research should develop targeted treatments and explore novel technologies to improve recovery outcomes. Clinicians should prioritize early screening for TBI and co-occurring conditions, while policymakers should improve access to specialized TBI care, ultimately enhancing veterans' long-term quality of life.

Traumatic brain injury (TBI) associated with facial fractures is a major public health concern worldwide. The rate of TBI in patients with mandibular fractures ranges from 21.3% to 39.6%. However, the risk factors for TBI in patients with mandibular fractures remain unknown. Our study evaluates these risk factors.

We retrospectively reviewed patients who presented with traumatic mandibular fractures in 2018 and 2019. Excluded were patients with no documentation of Glasgow Coma Scale. Our primary outcomes were: (1) prevalence of concomitant TBI on presentation defined as having a positive head computed tomography scan (hemorrhage, parenchymal contusion, diffuse axonal injury), or a negative scan with Glasgow Coma Scale < 15 or any neurologic symptom/sign; (2) prevalence of posttraumatic neurologic symptoms assessed at ≥4 weeks after injury. The mandibular injury severity score (MISS) was calculated for all patients. Bivariate analysis and multivariable logistic regression were performed.

Of 390 patients with mandibular fractures, 165 (42.3%) had concomitant TBI on presentation. Of those, 61% (n = 101) had mild TBI, 12% (n = 20) had moderate TBI, and 27% (n = 44) had severe TBI. Almost half of the mandibular fractures were due to assault (182 [47%]). Older age at injury and the presence of other facial fractures were associated with significantly greater odds of TBI on presentation (adjusted odds ratio 95% confidence interval [CI] 1.016 [1.001-1.032], P = 0.040; 2.457 [1.551-3.891], P < 0.001). Of 195 patients who were assessed at ≥4 weeks after injury, 99 (51%) had neurologic symptoms, most commonly facial numbness (74 [38%]). Mandibular body fracture and a high MISS were associated with significantly greater odds of having neurologic sequelae at ≥4 weeks after injury (adjusted odds ratio [95% CI] 3.12 [1.31-7.50], 1.12 [1.04-1.20]).

Older patients and those with mandibular body fractures and a high MISS may benefit from TBI screening and close longitudinal follow-up to identify and manage neurologic sequelae.

Traumatic brain injury (TBI) is a leading cause of mortality and long-term disability, with its pathophysiology encompassing both primary mechanical damage and secondary neuroinflammatory, metabolic, and biochemical alterations. These complex mechanisms contribute to the observed heterogeneous clinical outcomes, including neuroendocrine dysfunctions, post-traumatic seizures, and disorders of consciousness (DoC). Thyroid hormones (THs) play essential roles in synaptic plasticity, neurogenesis and neuronal homeostasis, and the hypothalamic-pituitary-thyroid (HPT) axis has recently emerged as a potential acute and chronic modulator of neurological and functional recovery following TBI, thereby hinting at the potential involvement of THs in post-TBI outcomes. While evidence suggests that alterations in the HPT axis may influence susceptibility to seizures, progression of DoC, and rehabilitation outcomes, an increased blood-brain barrier permeability in concert with dysregulated deiodinase activity and expanding oxidative stress have all been proposed as mechanisms linking THs to post-TBI neurological complications. This review aims to summarize current evidence on the potential role of the thyrotropic axis in neurological and rehabilitation outcomes following TBI.

Traumatic brain injury (TBI) is a heterogeneous disease characterized by brain damage and functional impairment caused by external forces. Under the influence of multiple mechanisms, TBI can cause synaptic dysfunction, protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammatory cascade reactions, resulting in a high disability and mortality rate for patients and a heavy burden on families and society. Exosomes are cell-derived vesicles that encapsulate a variety of molecules, including proteins, lipids, mRNAs, and other small biomolecules. Among these, exosomes derived from mesenchymal stem cells (MSCs) have garnered significant attention owing to their therapeutic potential in the nervous system, offering broad clinical applicability. Recent studies have demonstrated that MSC-derived exosome injections in traumatic brain injury models effectively mitigate local inflammatory damage and promote nerve regeneration following injury. Owing to their small size, challenging replication, ease of preservation, and low immunogenicity, MSC exosomes are emerging as a promising therapeutic strategy for traumatic brain injury. This review explores the pathogenesis of traumatic brain injury, the underlying mechanisms of MSC exosome action, and the potential clinical applications of MSC exosomes in the treatment of traumatic brain injury.

Guanxin II, proposed by Chen Keji (National master of traditional Chinese medicine), possesses neuroprotective effect. Interestingly, its simplified prescription Danshen-Chuanxiong-Honghua (DCH) can also clinically ameliorate cerebral impairment and improve spatial cognitive deficits, similar to the function of original formula.

We aimed to elucidate the rationality of DCH's natural existence, qualitatively identify DCH-derived phytochemicals, thereby to validate cerebral protective effect, and expose the potential mechanism of DCH and its main absorbed compound ferulic acid (FA).

The natural rationality of DCH's existence for treating TBI was verified using data mining. The qualitative analysis of DCH extract-derived phytochemicals was conducted through liquid chromatography with mass spectrometry (LC-MS). Controlled cortical impact (CCI) was chosen to establish TBI model. Neurological behavior tests, blood-brain barrier (BBB) permeability test, brain water content measurement, and proinflammatory factors consisting of IL-6, IL-1β, and TNF-α of plasma, and HPA axis-related hormone levels of DA, NA, 5-HT, ghrelin, and BDNF in hippocampus were analyzed by enzyme-linked immunosorbent assay. Network pharmacology was employed to predict potential targets and pathways of DCH intervening TBI. Growth hormone secretagogue receptor (GHSR) antagonist [D-Lys3]-GHRP-6 (D-Lys3) was injected intraperitoneally in TBI rats after waking up. Molecular docking and pharmacological experiment with D-Lys3 were used to verify the pathway.

Twenty-six phytochemicals were identified based on LC-MS. FA, as the primary contributor of DCH, alleviated disruption of BBB and reduced brain edema, suppressed the secretion of proinflammatory factors, such as IL-6, IL-1β, TNF-α, as well as HPA axis-related hormones such as DA, NA, and 5-HT, and ghrelin, and BDNF by regulating the Ghrelin/GHSR pathway. These results were validated by GHSR receptor antagonist, as well as molecule docking.

Taken together, DCH, when prescribed for the treatment of TBI, has a certain degree of reasonableness. FA, as the main absorbed component, demonstrated a similar function to DCH in improving the blood-brain barrier, promoting neural recovery, and anti-inflammatory effects in TBI rats, primarily via modulating Ghrelin/GHSR.

Traumatic brain injury commonly impairs attention and executive function and disrupts the large-scale brain networks that support these cognitive functions. Abnormalities of functional connectivity are seen in corticostriatal networks, which are associated with executive dysfunction and damage to neuromodulatory catecholaminergic systems caused by head injury. Methylphenidate, a stimulant medication that increases extracellular dopamine and noradrenaline, can improve cognitive function following traumatic brain injury. In this experimental medicine add-on study to a randomized, double-blind, placebo-controlled clinical trial, we test whether administration of methylphenidate alters corticostriatal network function and influences drug response. Forty-three moderate-severe traumatic brain injury patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Twenty-eight patients were included in the neuropsychological and functional imaging analysis (four females, mean age 40.9 ± 12.7 years, range 20-65 years) and underwent functional MRI and neuropsychological assessment after each block. 123I-Ioflupane single-photon emission computed tomography dopamine transporter scans were performed, and specific binding ratios were extracted from caudate subdivisions. Functional connectivity and the relationship to cognition were compared between drug and placebo conditions. Methylphenidate increased caudate to anterior cingulate cortex functional connectivity compared with placebo and decreased connectivity from the caudate to the default mode network. Connectivity within the default mode network was also decreased by methylphenidate administration, and there was a significant relationship between caudate functional connectivity and dopamine transporter binding during methylphenidate administration. Methylphenidate significantly improved executive function in traumatic brain injury patients, and this was associated with alterations in the relationship between executive function and right anterior caudate functional connectivity. Functional connectivity is strengthened to brain regions, including the anterior cingulate, that are activated when attention is focused externally. These results show that methylphenidate alters caudate interactions with cortical brain networks involved in executive control. In contrast, caudate functional connectivity reduces to default mode network regions involved in internally focused attention and that deactivate during tasks that require externally focused attention. These results suggest that the beneficial cognitive effects of methylphenidate might be mediated through its impact on the caudate. Methylphenidate differentially influences how the caudate interacts with large-scale functional brain networks that exhibit co-ordinated but distinct patterns of activity required for attentionally demanding tasks.

Nearly half of mild traumatic brain injury (mTBI) patients continue to experience residual neurological dysfunction, which may be attributed to exposure to stress. Ferroptosis, a newly discovered form of cell death, is increasingly recognized for its involvement in the pathophysiology of TBI. Understanding the mechanisms by which stress influences mTBI, particularly through ferroptosis, is crucial for the effective treatment and prevention of mTBI patients who are sensitive to stressful events. In our study, a mouse mTBI model was established. An acute restraint stress (RS) and a chronic unpredictable mild stress (CUMS) model then were applied to make acute and chronic stress, respectively. We found acute RS significantly delayed the recovery of reduced body weight and short-term motor dysfunctions and exacerbated cell insults and blood-brain barrier leakage caused by mTBI. Further studies revealed that acute RS exacerbates neuronal ferroptosis, pyroptosis, and apoptosis by promoting iron overloading in the neocortex following mTBI. Interestingly, the inhibition of ferroptosis with iron chelators, including deferoxamine and ciclopirox, reversed pyroptosis and apoptosis. Moreover, CUMS aggravated neurological dysfunctions (motor function, cognitive function, and anxiety-like behavior) and exacerbated brain lesion volume. CUMS also exacerbates ferroptosis, pyroptosis, and apoptosis by intensifying iron deposition, along with decreasing the expression of neuronal brain-derived neurotrophic factor and glucocorticoid receptor in the neocortex post mTBI. These effects were also mitigated by iron chelators. Our findings suggest that alleviating ferroptosis induced by iron deposition may represent a promising therapeutic approach for mTBI patients who have experienced stressful events.

Traumatic brain injury (TBI) is a burdensome condition frequently associated with an increased risk of psychiatric disorders. Although the exact molecular signaling pathways have not yet been fully defined, the compromised integrity of functional brain networks in regions such as the prefrontal cortex and anterior cingulate cortex has been linked to persistent symptoms, including depression, fatigue, and sleep disorders. Understanding how TBI affects neural physiology enables the development of effective interventions. One such strategy may be physical exercise, which promotes neural repair and behavioral rehabilitation after TBI. However, there are caveats to consider when interpreting the effects of physical exercise on TBI-induced mental health issues. This review will highlight the main findings from the literature investigating how different physical exercise protocols affect the progression of TBI-induced depression, fatigue, and sleep disturbances. Furthermore, we aim to explore potential neurobiological pathways that explain how physical exercise influences depression, fatigue, and sleep following TBI.

Traumatic brain injury (TBI), particularly at high altitudes (HA-TBI), is a leading cause of mortality and disability, yet clear diagnostic and treatment protocols are lacking. This study explores the early pathophysiological changes occurring within 24 h following HA-TBI, with a focus on differentially expressed proteins (DEPs) and phosphorylated proteins (DEPPs). Using a low-pressure hypoxic chamber to simulate high-altitude conditions combined with a controllable cortical impact (CCI) model, we established a rat model of HA-TBI. Neurological function was evaluated using the modified Neurologic Severity Score (mNSS), while neuropathological and inflammatory responses following HA-TBI were evaluated through hematoxylin and eosin (HE) staining, immunofluorescence, Western blot (WB), and Enzyme-Linked Immunosorbent Assay (ELISA). In-depth proteomic and phosphoproteomic analyses were performed on the cerebral cortex at 6, 12, and 24 h post-injury. Bioinformatic analysis identified time-dependent DEPs, revealing dynamic changes in mRNA metabolism, ATP metabolism, and MAPK signaling during the early stages of HA-TBI. Common DEPs at 6, 12, and 24 h post-injury were linked to complement and coagulation cascades. Time-dependent DEPPs influenced synaptic structure and neurotransmission, with early changes in glutamatergic synapses being especially pronounced. Key pathways, including the complement and coagulation cascades and dopaminergic synapses, emerged as central to the injury response. Furthermore, proteins such as AHSG, APOA1, GRIN2B, phospho-GSK3β-S9, and CAMK2G were identified as critical regulators in these pathways. WB validated these findings, offering new insights into the mechanisms underlying HA-TBI and highlighting potential therapeutic targets for early intervention in high-altitude trauma.

The present study aimed to clarify the onset of traumatic brain injury (TBI) and identify mortality-related risk factors in patients with severe TBI, to enable the early identification of high-risk individuals and timely implementation of prevention and treatment strategies to minimize mortality rates. Comprehensive database searches were conducted across Web of Science, PubMed, CINAHL and EMBASE, covering publications from database inception until October 17, 2023. Search terms in English included 'head trauma', 'brain trauma', 'mortality', 'death' and 'risk factor'. In total, two independent researchers screened and extracted the data on mortality onset and associated risk factors in patients with severe TBI. Meta-analysis was performed using R 4.2.2. A total of 33 cohort studies, including 71,718 patients with severe TBI, were selected for meta-analysis. The data indicated an overall mortality rate of 27.8% (95%CI: 22.5-33.2%) from database inception until October 17, 2023. Subgroup analysis revealed a mortality rate of 25.2% (95%CI: 20.2-30.1%) in developed countries, compared with 38.0% (95%CI: 21.4-54.7%) in developing countries. Additionally, the mean age of deceased patients was significantly higher compared with that of survivors (41.53±16.47). Key risk factors found to be associated with mortality included anemia [relative risk (RR), 1.42; 95%CI, 1.04-1.93], diabetes mellitus (RR, 1.40; 95%CI, 1.00-1.96), coagulopathy (RR, 4.31; 95%CI, 2.31-8.05), shock (RR, 3.41; 95%CI, 2.31-5.04) and systolic blood pressure≤90 mmHg (RR, 2.32; 95%CI, 1.65-3.27). Furthermore, pre-hospital intubation (RR, 1.48; 95%CI, 1.13-1.92),hypotension (RR, 2.04; 95%CI: 1.58, 2.63), hypoxemia (RR, 1.42; 95%CI: 1.13, 1.79), subdural hemorrhage (RR, 1.99; 95%CI: 1.50, 2.62), subarachnoid hemorrhage (RR, 1.64; 95%CI: 1.09, 2.47) and subdural hematoma (SDH; RR, 1.50; 95%CI: 1.04, 2.17). was identified to be a significant risk factor during hospitalization treatment. These results suggest that various factors, such as age, anemia, diabetes, shock, hypotension, hypoxemia, trauma scores and brain injury types, can all contribute to mortality risk in patients with severe TBI. Addressing these risk factors will likely be important for reducing mortality in this patient population.

Traumatic brain injury (TBI) leads to significant hippocampal neuronal loss, contributing to cognitive dysfunction. Our bioinformatics analysis of single-cell RNA sequencing data from hippocampal tissue following TBI revealed persistent neuronal loss and activation of ferroptosis-related pathways. Notably, Tyro3 expression was significantly upregulated, suggesting its potential role in neuronal ferroptosis. This finding was further validated in both in vivo and in vitro studies using a controlled cortical impact (CCI) model. We observed that Tyro3 knockdown exacerbated ferroptosis, while Tyro3 overexpression mitigated it. Moreover, treatment with the Tyro3 agonist Gal-3 conferred protective effects, improving both motor and cognitive functions through Tyro3 activation. These results highlight Tyro3 as a promising therapeutic target for TBI.

This retrospective cohort study aimed to identify predictive factors for patients with traumatic brain injury (TBI) requiring short (≤ 14 days) or long (≥ 15 days) rehabilitation length of stays (LOSs).The study was conducted in an acute rehabilitation hospital associated with a community-based tertiary medical center. Patients who were admitted to the acute inpatient rehabilitation unit with TBI between January 2020 and September 2022 were included (n = 197). The mean rehabilitation LOS of the 197 patients was 16.73 ± 9.4 days. A long rehabilitation LOS was associated with a higher rate of urinary tract infection in the rehabilitation facility (p = 0.002), a higher rate of lung infection in the inpatient rehabilitation facility (p = 0.003), unplanned readmission to acute care (p < 0.001), a longer LOS in acute care before admission to rehabilitation (p < 0.001), and a lower Section GG score on admission to rehabilitation (p < 0.001). The logistic regression model revealed having lower Section GG scores on admission to rehabilitation as the only factor predictive of a long rehabilitation LOS (odds ratio, 0.91; p < 0.001). Our study revealed that the Section GG score at admission to inpatient rehabilitation facilities is a predictor of rehabilitation LOS.

Traumatic brain injury (TBI) and spinal cord injury (SCI) are significant central nervous system injuries with epidemiological importance, particularly in the North Africa and the Middle East (NAME) region, which is diverse in public health aspects across its 21 countries.

This study aims to present an up-to-date assessment of the regional and national TBI and SCI burden and their causes in the NAME region from 1990 to 2021.

We utilized the Global Burden of Disease (GBD) results tool to gather relevant data. The analysis included TBI and SCI incidence, prevalence, and years lived with disability (YLDs) rates, along with absolute numbers and percent change trends by gender, age, and country from 1990 to 2021. We also examined the causes of TBI and SCI and identified the most common causes for each country.

In 2021, TBI age-standardized rates of incidence, prevalence, and YLDs were 333 (293, 380), 593 (553, 642), and 87 (63, 114) per 100,000 people, respectively. For SCI, the rates were 10 (7, 13), 256 (200, 344), and 78 (51, 115). Since 1990, incidence rates of TBI and SCI have decreased in most countries. Saudi Arabia, Afghanistan, and Yemen experienced increasing incidence rates for both injuries. Transport injuries and unintentional injuries were the primary causes of TBI and SCI, respectively, in most countries.

Despite global trends showing a decreased burden of TBI and SCI, the NAME region's public health systems should remain vigilant. Both injuries are epidemiologically significant and require continued public health interventions to manage and control them in this particular region.

Many patients with traumatic brain injury (TBI) across all levels of severity experience persistent psycho-emotional, cognitive, and somatic symptoms. Psychological network theory views disorders as intricate systems rather than discrete diseases. This study employs an exploratory network analysis method to uncover potential causal links among long-term TBI symptoms.

We examined persistent symptoms using secondary data from 250 TBI patients undergoing an inpatient "brain check" procedure. We constructed two partial correlation networks: one for the entire sample and another for a mild TBI subgroup, each consisting of 14 symptoms and three covariates. The symptoms and their connections were visualized in network graphs to identify potential causal, and structural indicators and centrality indices were calculated.

The analysis revealed two dense networks characterized by multiple complex connections. In the overall network, symptoms are clustered into psycho-emotional and cognitive communities, with attention deficits serving as a crucial link between them. One finding was that self-reported cognitive impairments do not align with objectively measured deficits. Within the mild TBI subgroup, PTSD emerges as a central node in the network.

Network analysis reveals the multidimensional and reciprocal nature of long-term TBI symptoms. Attention deficits bridge cognitive and psycho-emotional areas, whereas psycho-emotional symptoms influence self-perceived performance. Self-reported cognitive impairments should be emphasized in therapy as they are linked rather to sleep, visual disturbances, and anxiety than to objective deficits. Network analysis is valuable for understanding TBI symptom complexity and exploring treatment options. Future research should utilize longitudinal designs to validate our findings.

Increasing evidence suggests that ferroptosis, an iron-dependent form of cell death characterized by lipid peroxidation, may play a substantial role in the traumatic brain injury (TBI) pathophysiology. 3-n-butylphthalide (NBP), a compound extracted from the seeds of Apium graveolens Linn (Chinese celery) and used in China to treat ischemic stroke, has demonstrated encouraging anti-reactive oxygen species (ROS) effects. Ascertaining whether NBP can inhibit ferroptosis and its mechanism could potentially expand its use in models of neurological injury and neurodegenerative diseases.

In this study, we used erastin-induced in vitro ferroptosis models (HT22 cells, hippocampal slices, and primary neurons) and an in vivo controlled cortical impact mouse model. Our study revealed that NBP administration mitigated erastin-induced death in HT-22 cells and decreased ROS levels, lipid peroxidation, and mitochondrial superoxide indicators, resulting in mitochondrial protection. Moreover, the ability of NBP to inhibit ferroptosis was confirmed in organotypic hippocampal slice cultures and a TBI mouse model. NBP rescued neurons, inhibited microglial activation, and reduced iron levels in the brain tissue. The protective effect of NBP can be partly attributed to the inhibition of the AHR-CYP1B1 axis, as evidenced by RNA-seq and CYP1B1 overexpression/inhibition experiments in HT22 cells and primary neurons.

Our study underscores that NBP inhibition of the AHR-CYP1B1 axis reduces ferroptosis in neuronal damage and ameliorates brain injury.

Post-traumatic cerebral infarction (PTCI) is a severe complication resulting from traumatic brain injury (TBI), which can lead to permanent neurological damage or death. The investigation of the factors associated with PTCI and the establishment of predictive models are crucial for clinical practice.

We made a retrospective analysis of clinical data from 1484 TBI patients admitted to the Neurosurgery Department of a provincial hospital from January 2018 to December 2023. Predictive factors were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) and multivariable logistic regression analysis. Several machine learning (ML) classification models were developed and compared. The interpretations of the ML models' predictions were provided by SHAP values.

Key predictors included age, bilateral brain contusions, platelet count, uric acid, glucose, traumatic subarachnoid hemorrhage, and surgical treatment. The logistic regression (LR) model outperformed other ML algorithms, demonstrating superior performance in the test set with an AUC of 0.821, accuracy of 0.845, Matthews correlation coefficient (MCC) of 0.264, area under the receiver operating characteristic curve (AUROC) of 0.711, precision of 0.56, and specificity of 0.971. It had stable performance in the ten-fold cross-validation.

ML algorithms, integrating demographic and clinical factors, accurately predicted the risk of PTCI occurrence. Interpretations using the SHAP method offer guidance for personalized treatment of different patients, filling gaps between complex clinical data and actionable insights.

Traumatic brain injury (TBI) is one of the major causes of severe neurological disorders and long-term dysfunction in the nervous system. Besides inducing neurodegeneration, TBI alters stem cell activity and neurogenesis within primary neurogenic niches. However, the fate of dividing cells in other brain regions remains unclear despite offering potential targets for therapeutic intervention. Here, we investigated cell division and differentiation in non-neurogenic brain regions during the acute and delayed phases of TBI-induced neurodegeneration. We subjected mice to lateral fluid percussion injury (LFPI) to model TBI and analyzed them 1 or 7 weeks later. To assess cellular proliferation and differentiation, we administered 5-ethinyl-2'-deoxyuridine (EdU) and determined the number and identity of dividing cells 2 h later using markers of neuronal precursors and astro-, micro-, and oligodendroglia. Our results demonstrated a significant proliferative response in several brain regions at one week post-injury that notably diminished by seven weeks, except in the optic tract. In addition to active astro- and microgliosis, we detected oligodendrogenesis in the striatum and optic tract. Furthermore, we observed trauma-induced neurogenesis in the striatum. These findings suggest that subcortical structures, particularly the striatum and optic tract, may possess a potential for self-repair through neuronal regeneration and axon remyelination.

Health-related behavioral changes may occur following traumatic brain injury. We focused on understanding the impact of mild traumatic brain injury (TBI) on health-related behaviors and identifying factors associated with such changes. We utilized health check-up records from the Korean National Health Insurance Service database spanning January 1, 2009, to December 31, 2017. The sample included 49,212 patients diagnosed with mild TBI and 1:1 matched controls who participated in national health check-ups in 2009-2010, 2011-2012, and 2016-2017. Multivariable logistic regression analysis was utilized to examine the association between mild TBI and short- and long-term health-related behavioral changes. Mild TBI was significantly associated with an increased risk of insufficient physical activity at the short- [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 - 1.07] and long-term (OR, 1.06; 95% CI, 1.03 - 1.09) follow-ups. Age ≥ 65 years and female sex were significant effect modifiers for insufficient physical activity (OR, 1.11; 95% CI, 1.02 - 1.21) and smoking (OR, 1.31; 95% CI, 1.14 - 1.51), respectively. Mild TBI may lead to detrimental health-related behavioral changes, varying by age and sex. Thus, age- and sex-specific interventions may be needed to address these changes.

Traumatic brain injury (TBI) is a predominant cause of long-term disability in adults, yet the molecular mechanisms underpinning the neuropathological processes associated with it remain inadequately understood. Neutrophil cytosolic factor 1 (NCF1, also known as p47phox) is one of the cytosolic components of NADPH oxidase NOX2. In this study, we observed a reduction in the volume of TBI-induced brain lesions in NCF1-knockout mice compared to controls. Correspondingly, the neuronal loss induced by TBI was mitigated in the NCF1-knockout mice. Behavioral analysis also demonstrated that the motor coordination deficit following TBI was mitigated by the depletion of NCF1. Mechanistically, our findings revealed that NCF1 deficiency attenuated TBI-induced inflammatory responses by inhibiting the release of proinflammatory factors and reducing neutrophil infiltration into the brain parenchyma. Additionally, our results indicated that NCF1 deficiency significantly decreased the levels of reactive oxygen species in neutrophils. Taken together, our findings indicate that NCF1 plays a crucial role in the regulation of brain injury and secondary inflammation post-TBI.

Traumatic brain injury (TBI) represents a common and severe medical condition necessitating prompt risk stratification to enhance patient outcomes. Although substantial research has been conducted on the prognostic utility of various biomarkers for TBI, no single biomarker has been definitively recognized as the most precise predictor of disease outcomes. In comparison to other markers, the neutrophil-albumin ratio (NAR) has emerged as a cost-effective and reproducible inflammatory biomarker, demonstrating potential in evaluating the severity of inflammation and prognosticating outcomes in infections and cerebrovascular diseases. This study evaluated the prognostic significance of the NAR in comparison to two other readily accessible and cost-effective composite indices: the Neutrophil-Lymphocyte Ratio (NLR) and the Platelet-Lymphocyte Ratio (PLR) in individuals with TBI. We conducted a retrospective cohort analysis involving 297 hospitalized TBI patients, gathering comprehensive demographic, anthropometric, medical, clinical, laboratory, and imaging data to assess the expression changes of these biomarkers. Our findings suggest that both the NAR and the NLR possess predictive value regarding prognosis following TBI. However, receiver operating characteristic (ROC) curve analysis revealed that NAR outperformed NLR as a prognostic predictor. In conclusion, our examination of blood biochemistry composite indicators indicates that, while both NAR and NLR serve as significant prognostic markers, NAR is a more effective predictor of outcomes in patients with TBI.

Traumatic brain injury (TBI) is associated with various endocrine abnormalities, including pituitary axis dysfunction. Understanding the prevalence and temporal patterns of these dysfunctions is crucial for effective clinical management. This study aimed to systematically review the literature and conduct a meta-analysis to determine the prevalence of pituitary axis dysfunction following TBI, assess temporal patterns across different post-injury durations, and identify potential contributing factors. A comprehensive search was conducted across multiple electronic databases between 1st of January 2000 until 31st March 2024. Studies reporting the prevalence of pituitary axis dysfunction post-TBI were included. Pooled estimates with 95% confidence intervals (CIs) were calculated using random-effects models in the R statistical software. Subgroup analyses were performed based on duration post-TBI (< 3 months, 3-6 months, 6-12 months, > 12 months) to explore temporal variations. Heterogeneity was assessed using the I^2 statistic. A total of 52 studies were included in the meta-analysis, encompassing 7367 participants. The pooled estimate for the prevalence of any pituitary axis dysfunction post-TBI was 33% (95% CI [28%; 37%]). Subgroup analysis by duration revealed varying prevalence rates: < 3 months (40%, 95% CI [27%; 53%]), 3-6 months (31%, 95% CI [15%; 47%]), 6-12 months (26%, 95% CI [19%; 33%]), and > 12 months (32%, 95% CI [26%; 38%]). Prevalence of multiple axes affection was 7% (95% CI [6%; 9%]), with varying rates across durations. Specific axes affection varied: Growth Hormone (GH) deficiency was 18% (95% CI [14%; 21%]), adrenocorticotropic hormone (ACTH) deficiency was 10% (95% CI [8%; 13%]), pituitary-gonadal axis hormones deficiency was 16% (95% CI [12%; 19%]), and thyroid-stimulating hormone (TSH) deficiency was 6% (95% CI [5%; 7%]). This meta-analysis highlights a significant prevalence of pituitary axis dysfunction following TBI, with temporal variations observed across different post-injury durations. The findings underscore the importance of tailored clinical management strategies based on the duration and type of dysfunction. Further research addressing potential contributing factors is warranted to enhance understanding and management of these conditions.

Traumatic brain injury is a highly irreversible process that consists of primary as well as secondary injury which develops and progresses over months to years, leading to cognitive dysfunctions. Vitamin B12 received considerable interest due to its potential therapeutic properties. The pathways of vitamin B12 are closely related to neuronal survival but its effects on the pathophysiology of injury with respect to cognition is a relatively unexplored area of research. In this study, we investigated, the effect of vitamin B12 and its involvement in neuroprotection on TBI-induced pathophysiology in male Swiss albino mice. Our findings suggested that vitamin B12 supplementation improves TBI-mediated neurological impairments, spatial and recognition memory, and anxiety-like behavior. Furthermore, the oxidative stress was reduced by declined homocysteine level with vitamin B12 supplementation validating declined expression of astrocytes and TBI biomarkers. The studies on neuronal morphology revealed that vitamin B12 supplementation increases the dendritic arborization and density of mushroom and filopodia-shaped spines and further increases the expression of synaptic plasticity-related genes and proteins. Taken together, our findings reveal that, supplementation of vitamin B12 restored the TBI-induced downregulation of dendritic arborization, and spine density which ultimately increases synaptic plasticity, cell survival, and recovery of cognitive dysfunctions.

Traumatic brain injury (TBI) exhibits high prevalence and mortality, but current treatments remain suboptimal. Traditional Chinese medicine (TCM) has long been effectively used for TBI intervention. Moreover, the recently discovered iron-dependent cell death pathway, known as ferroptosis, characterized by lipid peroxidation, as a key target in TCM-based treatments for TBI. This review provides a comprehensive overview of the latest advancements in TCM strategies targeting ferroptosis in TBI therapy, covering natural product monomers, classic formulas, and acupuncture/moxibustion. The review also addresses current challenges and outlines future research directions to further advance the development and application of TBI management strategies.

Mild traumatic brain injury (mTBI) is a common occurrence around the world, associated with a variety of blunt force and torsion injuries affecting all age groups. Most never reach medical attention, and the identification of acute injury and later clearance to return to usual activities is relegated to clinical evaluation-particularly in sports injuries. Advanced structural imaging is rarely performed due to the usual absence of associated acute anatomic/hemorrhagic changes. This review targets physiologic imaging techniques available to identify subtle blood-brain barrier dysfunction and white matter tract shear injury and their association with chronic traumatic encephalopathy. These techniques provide needed objective measures to assure recovery from injury in those patients with persistent cognitive/emotional symptoms and in the face of repetitive mTBI.

The secondary insult in the aftermath of traumatic brain injury (TBI) causes detrimental and self-perpetuating alteration in cells, resulting in aberrant function and the death of neuronal cells. The secondary insult is mainly driven by activation of the neuroinflammatory pathway. Among several classical pathways, the cGAS-STING pathway, a primary neuroinflammatory route, encompasses the cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and downstream signaling adaptor. Recently, the cGAS-STING research domain has gained exponential attention. The aberrant stimulation of cGAS-STING machinery and corresponding neuroinflammation have also been reported after TBI. In addition to the critical contribution to neuroinflammation, the cGAS-STING signaling also provokes neuronal cell death through various cell death mechanisms. This review highlights the structural and molecular mechanisms of the cGAS-STING machinery associated with TBI. We also focus on the intricate relationship and framework between cGAS-STING signaling and cell death mechanisms (autophagy, apoptosis, pyroptosis, ferroptosis, and necroptosis) in the aftermath of TBI. We suggest that the targeting of cGAS-STING signaling may open new therapeutic strategies to combat neuroinflammation and neurodegeneration in TBI.

The Renin Angiotensin System (RAS) plays a pathophysiological role in traumatic brain injury (TBI) but the evidence of its involvement in mild TBI (mTBI) is still limited. We aimed at investigating the levels of components from both the classical and counter-regulatory axis of the RAS in a mTBI animal model. Mice with mTBI displayed enhanced ACE/Ang II/AT1R axis ipsilateral- and contralaterally to the trauma in the hippocampus and prefrontal cortex during acute (24 and 72 h) and later (30 days) timepoints. Increase in Ang-(1-7) levels alongside reduction in Mas receptor expression in hippocampus and prefrontal cortex was also observed after injury. Conversely, mTBI-mice presented higher expression of AT2 receptor in the contralateral hippocampus and the ipsilateral prefrontal cortex. Importantly, treatment with telmisartan, an AT1R blocker, and perindopril, an ACE inhibitor, were able to prevent mTBI-associated locomotor activity impairment and anxiety-like behavior, corroborating the involvement of RAS in the pathophysiology of mTBI. We provided original evidence that components of classical and alternative RAS axes undergo alterations in key brain areas following a mTBI in a time and hemisphere dependent manner. Our findings also open new avenues for investigating the therapeutic potential of RAS components in mTBI.

Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown.

To investigate the mechanism by which Pae regulates ferroptosis after TBI.

The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI.

Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53.

Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.

Central nervous system (CNS) disorders have a complicated pathogenesis, and to date, no single mechanism can fully explain them. Most drugs used for CNS disorders primarily aim to manage symptoms and delay disease progression, and none have demonstrated any pathological reversal. Fucoidan is a safe, sulfated polysaccharide from seaweed that exhibits multiple pharmacological effects, and it is anticipated to be a novel treatment for CNS disorders. To assess the possible clinical uses of fucoidan, this review aims to provide an overview of its neuroprotective mechanism in both in vivo and in vitro CNS disease models, as well as its pharmacokinetics and safety. We included 39 articles on the pharmacology of fucoidan in CNS disorders. In vitro and in vivo experiments demonstrate that fucoidan has important roles in regulating lipid metabolism, enhancing the cholinergic system, maintaining the functional integrity of the blood-brain barrier and mitochondria, inhibiting inflammation, and attenuating oxidative stress and apoptosis, highlighting its potential for CNS disease treatment. Fucoidan has a protective effect against CNS disorders. With ongoing research on fucoidan, it is expected that a natural, highly effective, less toxic, and highly potent fucoidan-based drug or nutritional supplement targeting CNS diseases will be developed.

Traumatic brain injury (TBI) often precipitates a cascade of neurophysiological alterations, impacting structures such as the optic nerve and ocular motor system. However, the literature lacks expansive investigations into the longitudinal changes in the optic chiasm and its relationship with the clinical recovery of visual processing. This study aimed to scrutinize longitudinal changes in optic chiasm volume (OCV) and establish the relationship of OCV with process speed index at 12 months post-injury. Process speed index is derived from Wechsler Adult Intelligence Scale IV.

Thorough cross-sectional and longitudinal analyses were executed, involving 42 patients with moderate to severe TBI and 35 healthy controls. OCV was acquired at 3, 6, and 12 months post-injury using T1-weighted images. OCV of healthy controls and that of patients with TBI at 3, 6, and 12 months post-injury were compared using a Mann-Whitney U test. A multiple linear regression model was constructed to assess the association between OCV and PSI and to predict PSI at 12 months post-injury using OCV at 3 months post-injury.

OCV of patients with TBI was significantly larger compared to healthy controls, persisting from 3 to 12 months post-injury (p < 0.05). This increased OCV negatively correlated with PSI at 12 months post-injury, indicating that larger OCV sizes were associated with decreased PSI (p = 0.031). Furthermore, the multiple linear regression model was significant in predicting PSI at 12 months post-injury utilizing OCV at 3 months post-injury (p = 0.024).

For the first time, this study elucidates the increased OCV and the significant association between OCV in sub-chronic stage and PSI at 12 months post-injury, potentially providing clinicians with a tool for anticipatory cognitive rehabilitation strategies following TBI.

Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment.

Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes (n = 177) between the ages of 27 and 85 (M = 54.1, SD = 14.7).

Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms.

Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p = <.001). Further analysis revealed that the number of mTBI + LOC events predicted neurobehavioral symptoms indirectly through both depression (B = 0.85, 95% CI = [0.27, 1.52) and insomnia (B = 0.81, 95% CI = [0.3, 1.4]). Further, the direct effect of mTBI + LOC events on neurobehavioral symptoms became non-significant when depression and insomnia were added to the model (B = 0.78, SE = 0.45, p = 0.08).

Findings support LOC at time of injury as an important predictor of long-term outcomes. Additionally, results suggest depression and insomnia as potential mediators in the association between mTBI + LOC and neurobehavioral symptoms. These findings provide justification for early depression and insomnia symptom monitoring following mTBI + LOC.

The aim of this report is to provide a comprehensive overview of clinical trials and protocols related to traumatic brain injury over the past two decades.

We collected information on clinical trials related to traumatic brain injury (TBI) from the ClinicalTrials.gov database, identified key categorical variables, and assessed their characteristics.

A total of 367 TBI-related trials were identified for analysis. All identified trials were interventional clinical trials. Most trials were small-scale, with 75.2% enrolling 1-100 participants, and only about 20% were funded by industry or the National Institutes of Health (NIH). In most trials, participants were gender-neutral (96.5%), and the primary age group was adults and older adults (56.9%). Of all identified TBI trials, 78.2% were randomized, and 69.4% were blinded. Additionally, the primary purpose of 297 trials (80.9%) was treatment, with drug therapy as the most common intervention. A total of 153 trials (41.7%) were completed; however, only 58 trials submitted results to the registry. Furthermore, 81 trials (22.1%) were discontinued early, primarily due to recruitment problems. Clinical trials started between 2004 and 2013 reported a higher proportion of results compared with those started between 2014 and 2023 (35.1% vs. 11.1%, p < 0.001). In addition, between 2014 and 2023, there was an increase in trials for diagnostic purposes (2.4% vs. 6.5%, p < 0.001).

Based on the data collected from the ClinicalTrials.gov, our study reveals that most clinical trials related to TBI focus on drug-related treatments, underreporting remains a significant concern, and greater emphasis should be placed on improving the publication and dissemination of clinical trial results.

In preclinical traumatic brain injury (TBI) research, the animal model should be selected based on the research question and outcome measures of interest. Direct side-by-side comparisons of different injury models are essential for informing such decisions. Here, we used immunohistochemistry to compare the outcomes from two common models of TBI, lateral fluid percussion (LFP) and repeated mild weight drop (rmWD) in adult female and male Wistar rats. Specifically, we measured the effects of LFP and rmWD on markers of cerebrovascular and tight junction disruption, neuroinflammation, mature neurons, and perineuronal nets in the cortical site of injury, cortex adjacent to injury, dentate gyrus, and the CA 2/3 area of the hippocampus. Animals were randomized into the LFP or rmWD group. On day 1, the LFP group received a craniotomy, and on day 4, injury (or sham procedure; randomly assigned). The rmWD animals underwent either injury or isoflurane only (randomly assigned) on each of those 4 days. Seven days after injury, brains were harvested for analysis. Overall, our observations revealed that the most significant disruptions were evident in response to LFP, followed by craniotomy only, whereas rmWD animals showed the least residual changes compared with isoflurane-only controls, supporting consideration of rmWD as a mild injury. LFP led to longer-lasting disruptions, perhaps more representative of moderate TBI. We also report that craniotomy and LFP produced greater disruptions in females relative to males. These findings will assist the field in the selection of animal models based on target severity of postinjury outcomes and support the inclusion of both sexes and appropriate control groups.

This study aimed to investigate the effects of traumatic brain injury (TBI) on employment status, household income, and the development of new disabilities among survivors, as well as its correlation with mortality rates over a 2-year period.

In this nationwide population-based cohort study, we screened all patients admitted to the intensive care unit (ICU) because of TBI between January 1, 2010, and December 31, 2018, in South Korea. Among them, patients who were alive for > 1 year were considered TBI survivors. Changes in unemployment, decreased household income, and newly acquired disabilities were evaluated one year after the date of ICU admission due to TBI.

In total, 78,420 TBI survivors were included in this study. Among them, 5.4 %, 22.5 %, and 8.6 % of the TBI survivors experienced unemployment, decreased household income, and newly acquired disabilities within one year after the date of ICU admission, respectively. A longer ICU stay, comorbidities, hospital admission through the emergency room, increased total cost of hospitalization, and mechanical ventilatory support were associated with unemployment, decreased household income, and newly acquired disabilities. Among the three factors, the newly acquired disability was associated with a 27 % increase in 2-year all-cause mortality (hazard ratio: 1.27, 95 % confidence interval: 1.17-1.39; P < 0.001), while unemployment and decreased household income were not significantly associated (P = 0.371 and P = 0.105, respectively).

A significant number of individuals in South Korea who survived TBI faced challenges such as unemployment, reduced household income, and the acquisition of new disabilities within a year of being admitted to the ICU. In addition, the study found that individuals who developed a new disability after TBI had a higher risk of mortality within two years.

Astrocytes are the most abundant glial cells in the central nervous system; they participate in crucial biological processes, maintain brain structure, and regulate nervous system function. Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins, peptides, nucleotides, and lipids secreted from their cellular sources. Increasing evidence shows that exosomes participate in a communication network in the nervous system, in which astrocyte-derived exosomes play important roles. In this review, we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system. We also discuss the potential research directions of the exosome-based communication network in the nervous system. The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain. New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.

MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements.

Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium observational study of the late effects of mTBI in combat with and without a history of mTBI were examined. A series of regression models with link functions appropriate for the model outcome were used to evaluate the relationships among imaging measures and clinical features of mTBI. Each model included acquisition site, participant sex, and age as covariates. Separate regression models were fit for each region of interest where said region was a predictor.

After controlling for multiple comparisons, no significant main effect was noted for comparisons between veterans and service members with and without a history of mTBI. However, blast-related mTBI were associated with volumetric reductions of several subregions of the corpus callosum compared to non-blast-related mTBI. Several volumetric (i.e., hippocampal subfields, etc.) and diffusion (i.e., corona radiata, superior longitudinal fasciculus, etc.) MRI findings were noted to be associated with an increased number of repetitive mTBIs versus.

In deployment-related mTBI, significant findings in this cohort were only observed when considering mTBI sub-groups (blast mechanism and total number/dose). Simply comparing healthy controls and those with a positive mTBI history is likely an oversimplification that may lead to non-significant findings, even in consortium analyses.