Journal of Neurotrauma

This scoping review aimed to systematically describe the literature reporting the relationship between guidelines adherence and outcomes in children with severe traumatic brain injury (TBI). The search for articles of interest was performed in the Pubmed, Embase, Cochrane Library, and Google Scholar databases. Two investigators independently screened publications from 2000 to March 2024 reporting the relationship between the implementation of a protocolized management or adherence to guidelines for severe pediatric TBI management and patient outcomes. Discrepancies regarding study eligibility were resolved by consensus, and with a third reviewer if needed. Inclusion criteria included pediatric severe TBI, reporting of clinical outcomes, with comparison of whether guidelines were respected or not. Among 2141 articles identified after the systematic search, eight articles were included in the review. The implementation of a management protocol for severe TBI was reported in five studies and was associated with a reduction in mortality and an improvement in functional prognosis. Three articles also highlighted a statistical association between adherence to guidelines and improved outcomes. In conclusion, guidelines adherence after a pediatric severe TBI was associated with improved survival and functional patient outcomes in all studies identified, although the strength of this observation is limited by the observational or pre–post design of all included studies.

Mild traumatic brain injury (mTBI) is a global health concern that remains difficult to clinically evaluate due to variable diagnostic criteria and a lack of objective biomarkers. Diffusion tensor imaging (DTI) has been shown to be a sensitive measure of microstructural injury caused by head injury that cannot be visualized by conventional neuroimaging, which may potentially aid in the diagnosis and prognosis of mTBI. This review seeks to evaluate the available literature concerning the role of DTI in evaluating microstructural alterations in white matter (WM) associated with mTBI. An initial systematic search from PubMed, CENTRAL, Embase, MEDLINE, Web of Science, and Scopus yielded 1507 articles published between 2007 and 2024. A total of 79 studies met the full eligibility criteria for inclusion in this qualitative synthesis. The majority of studies demonstrated DTI abnormalities in the setting of acute, chronic, and remote mTBI, predominantly in the WM tracts of the corpus callosum, corona radiata, internal capsule, and longitudinal fasciculus. Many studies identified associations between DTI parameters and clinical measures of mTBI, such as cognitive performance, executive functioning, and comorbidities, including post-concussion syndrome and post-traumatic stress disorder. Overall, the weight of evidence in this review supports the cautious integration of DTI in the clinical assessment of mTBI. The observed discrepancies reported in the literature on DTI may be explained by significant variability in study design, analytical technique, and measured clinical outcomes. Further research that implements consistent methodology is crucial to fully realize the use of DTI as an imaging biomarker of mTBI.

Traumatic brain injury (TBI) occurs in millions of people globally each year, with mild TBI (mTBI) representing over 90% of cases. Despite the common assumption of full recovery, significant disturbances persist in many patients with mTBI, including cognitive deficit, headache, dizziness, sleep problems, and symptoms of post-traumatic stress disorder (PTSD). Given that effective treatment is still scarce, the present study investigated the efficacy of transcranial photobiomodulation (tPBM) as an intervention for improving these sequelae in patients with mTBI. In this randomized placebo-controlled trial, 17 patients with mTBI were recruited. Participants were randomized to receive both real and sham tPBM conditions with a counterbalanced order, with a 1-week washout between interventions. Assessments were conducted at baseline, after real tPBM, and after sham tPBM. These included neuropsychological tests, measurements of oxygenated hemoglobin using functional near-infrared spectroscopy during a visual working memory task, and self-rated questionnaires assessing sleep quality, physical post-concussion symptoms, pain intensity, and PTSD symptoms. Compared with the baseline, participants demonstrated significant improvements. After receiving tPBM, patients showed enhanced cognitive efficiency, as evidenced by improved visual working memory performance, better learning in verbal memory tests, improved subjective sleep quality, fewer physical post-concussion symptoms, reduced pain intensity, and decreased PTSD symptoms. In contrast, no significant improvement was observed after patients received the sham tPBM. In addition, the statistically significant improvement in behavioral symptoms also reached the minimal clinically important difference, suggesting clinical significance. These findings support the potential of tPBM as a safe, non-invasive clinical intervention for cognitive deficits and associated symptoms in mTBI. Further exploration is encouraged to evaluate tPBM as a rehabilitation strategy for enhancing recovery in TBI patients.

The objective of this study was to compare the effectiveness of Brock string vision therapy (BSVT) with usual care (UC) for receded near point of convergence (NPC) following concussion. This study employed a single-blind, randomized controlled trial design involving participants aged 11–30 years within 10 days of a concussion. Participants with receded NPC (i.e., mean NPC ≥5 cm) were randomized to either BSVT or UC. The BSVT group was prescribed BSVT exercises (5 reps, 2× daily, using ∼3 meters string with three colored beads). The UC group was prescribed symptom-specific management strategies (i.e., breaks during reading or other visual tasks) and behavioral management (e.g., sleep, hydration, diet) until follow-up (7–14 days post-enrollment). Two-way mixed effects analyses of variance examined the interaction between group (BSVT, UC) and time (enrollment, follow-up) on mean NPC (primary outcome) and secondary outcomes (e.g., Concussion Clinical Profile Screen [CP Screen]). Fifty participants were enrolled, with 25 in BSVT (age = 15.8 ± 4.1, 44% F, 84% sport-related concussion [SRC]) and 25 in UC (age = 17.9 ± 4.8, 36% F, 60% SRC). Results supported an interaction in the BSVT group for NPC (F[1, 48] = 5.3, p = 0.026, η_p ² = 0.10) and CP Screen Neck (F[1, 43] = 4.9, p = 0.033, η_p ² = 0.10). The BSVT group exhibited greater improvement in mean NPC distance (−8.9 cm, 95% confidence interval [CI] = −12.1, −5.7, p < 0.001) than the UC group (−3.8 cm, 95% CI = −6.9, −0.6, p = 0.02), and greater improvement in CP Screen Neck symptoms (−0.6, 95% CI, −1.1, −0.03, p = 0.039) than the UC group (0.27, 95% CI, −0.3, 0.8, p = 0.32). BSVT improved mean NPC distance compared with UC, suggesting that this simple, inexpensive, and early intervention may be effective for treating receded NPC following concussion.

Targeted manipulation of dietary omega-3 and omega-6 fatty acids has previously been shown to decrease nontraumatic headaches in controlled trials. This study assessed the effects of a diet high in omega-3 fatty acids and low in omega-6 linoleic acid (H3L6 diet) on headache frequency and severity, headache impact, and plasma nociceptive mediators in a persistent post-traumatic headache (pPTH) population. One hundred and twenty-two participants with pPTH were randomized 1:1 to 12 weeks of either the H3L6 (n = 62) or a control (n = 60) diet. A priori primary end-points were the plasma levels of the antinociceptive docosahexaenoic acid (DHA) derivative 17-hydroxy-DHA and the Headache Impact Test (HIT-6) score. Secondary end-points included headache days/month and average daily headache pain intensity (0–10 scale). Statistical analyses followed intention-to-treat principles and were adjusted for baseline values. Relative to the control group, the H3L6 group significantly reduced headache days/month (−2.1, 95% confidence interval [CI]: −3.5 to −0.8, p = 0.002) and average headache intensity (−0.9, 95% CI: −1.2 to −0.5, p < 0.001) and increased circulating 17-hydroxy-DHA (nanograms/milliliter; difference 0.07, 95% CI: 0.02–0.11, p = 0.003), although it did not significantly improve HIT-6 scores (−1.6, 95% CI: −4.0 to 0.8, p = 0.18). In conclusion, the H3L6 diet reduced headache pain and increased antinociceptive mediators, supporting its potential as an adjunct nonpharmacological pPTH therapy.

Traumatic brain injury (TBI) affects millions globally each year, with mild TBI comprising about 75% of cases. While most mild TBI symptoms are resolved within 3 months, some patients experience persistent issues. This study aimed to identify underlying mechanisms contributing to decrements in fluid cognitive abilities in chronic (>6 months) mild-to-moderate TBI. Specifically, the study focused on the relationships between cognitive performance, white matter integrity, TBI-related symptoms, and blood biomarkers, which are thought to be indicative of biological processes including neuronal injury (neurofilament light [NF-L], neurofilament heavy, ubiquitin C-terminal hydrolase-L1), vascular injury (vascular endothelial growth factor A), glial injury (glial fibrillary acidic protein [GFAP]), neurodegeneration (tau, phosphorylated-tau), immune response (GFAP immunoglobulin G), and inflammation (tumor necrosis factor-α, interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, interferon-γ, and macrophage inflammatory protein-1α). The final study sample included 57 participants (42 males, 15 females) aged 19–59 with a history of chronic, remote mild-to-moderate TBI. Participants underwent cognitive and behavioral testing, neuroimaging, and a blood draw. Diffusion-weighted magnetic resonance imaging was used to assess white matter integrity in tracts connecting frontal and parietal regions with fractional anisotropy utilized as the metric. Blood samples were analyzed for TBI-related biomarkers. The study found that higher fluid cognition scores were associated with higher white matter integrity in frontal–parietal networks, fewer reported TBI-related symptoms, and mixed biomarker and cytokine levels. Inflammatory processes were linked to lower fractional anisotropy in white matter pathways, more reported symptoms, and increased biomarkers of injury. Higher white matter integrity was also associated with fewer reported neurobehavioral symptoms. The findings provide evidence for a complex interplay of ongoing neuroinflammatory processes, white matter integrity, symptomology, and cognitive function in chronic mild-to-moderate TBI. The results underscore the importance of considering both structural brain changes and systemic responses in understanding the long-term effects of TBI. The observed correlations between cognitive deficits, white matter disruptions, and biomarker profiles suggest potential avenues for targeted interventions aimed at mitigating these effects in TBI patients.

Many women survivors of intimate partner violence (IPV) experience traumatic brain injury (TBI) due to physical violence, with a large portion of these women exposed to repetitive IPV-TBI. Limited research has examined neurological outcomes following repetitive IPV-TBI among survivors. The few existing studies have observed both structural and functional effects on neuroimaging. This pilot investigation is the first case-control study to assess differences in white matter between women survivors of IPV with and without repetitive IPV-TBI history. Participants underwent diffusion tensor imaging (DTI) and cognitive testing to compare white matter integrity between groups and assess the association between white matter integrity and fluid cognitive functioning. Participants were recruited from shelters, IPV service organizations, and the local community in Kentucky, USA. The final sample included 11 women with repetitive IPV-TBI (mean [M] = 34.2 years old, standard deviation [SD] = 7.3; 54.5% White; 81.8% with ≥12 years of education) and 11 women survivors without IPV-TBI history (M = 28.4 years old, SD = 9.7; 72.7% White; 90.9% with ≥12 years of education). Women completed the Brain Injury Screening Questionnaire, NIH Toolbox Cognition Battery, and DTI. Women with and without repetitive IPV-TBI were compared using tract-based spatial statistics (TBSS), which involved voxel-wise comparisons of fractional anisotropy (i.e., estimating white matter integrity) across groups using threshold-free cluster enhancement. Group differences in the corpus callosum, primarily posterior, and anterior thalamic radiation, primarily left, were noted. Lower white matter integrity was associated with reduced fluid cognitive functioning in the full sample among clusters that differed across groups (rho = −0.44, p = 0.040), but this association was nonsignificant when stratified by group (repetitive IPV-TBI: rho = −0.37, p = 0.259; no IPV-TBI: rho = 0.06, p = 0.873). Results from this case-control study suggest that repetitive IPV-TBI history corresponded with lower white matter integrity, most prominently in the posterior corpus callosum. Lower white matter integrity also correlated with reduced fluid cognitive ability across the study sample, regardless of IPV-TBI status. Despite a small sample size and cross-sectional design, this study builds on early neuroimaging research on IPV-TBI, further documenting the physical neurological effects of repetitive IPV-TBI among women survivors. Future research on IPV-TBI should assess whether white matter integrity among survivors corresponds with functional impairment, remains stable or progressive over time, or responds to intervention to improve brain health in this community.

Traumatic brain injuries (TBIs) account for over 2.5 million emergency department (ED) visits each year in the United States. The bulk of TBI research in acute care settings has focused exclusively on individuals who receive computed tomography (CT) scanning. Recently, more sensitive TBI assessment tools have been identified, including blood biomarkers such as glial fibrillary acidic protein (GFAP) and magnetic resonance imaging (MRI) of white matter microstructural integrity. These methods can evaluate for evidence of TBI in CT-negative patients. However, limited prior work has investigated the relationship between blood GFAP levels and white matter microstructural integrity. The present study examined the association between acute (≤72 h) GFAP levels and white matter microstructural integrity at 2 weeks post-trauma among ED patients (n = 328) recruited after a qualifying traumatic experience. We hypothesized that acute GFAP concentrations would be associated with disrupted microstructural integrity, quantified with Tract-Based Spatial Statistics-derived diffusion tensor imaging (DTI) metrics (reduced fractional anisotropy and increased axial diffusivity [AD], radial diffusivity, and mean diffusivity), in tracts previously shown to be vulnerable to TBI. Our secondary hypothesis was that there would be a stronger association between GFAP levels and white matter integrity among female relative to male trauma survivors, in line with previous literature suggesting that females’ axons are less resilient to stretch injury. To test the primary hypothesis, we fit four sets of linear regression models to assess the association between natural log-transformed acute GFAP concentration and DTI metrics for 15 white matter regions of interest (ROIs). The false discovery rate (FDR) was controlled at 0.05 for each set of models. Models were adjusted for age, sex, neuroimaging site, and a composite lifetime traumatic stress variable. To test the secondary hypotheses, we fit identical sets of linear regression models, with an additional interaction term between sex and ln(GFAP). We followed up all significant results surviving FDR correction with correlational tractography to examine the location and direction of tracts associated with the DTI metric passing through those ROIs. We observed significant and positive associations between acute GFAP and AD in the parahippocampal cingulum (B = 1.416 × 10⁻⁵, standard error [SE] = 4.806 × 10⁻⁶, p = 0.003, FDR-corrected p = 0.026), and the sagittal stratum (B = 1.012 × 10⁻⁵, SE = 3.438 × 10⁻⁶, p = 0.003, FDR-corrected p = 0.026), including fibers of the inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus. Furthermore, the association between GFAP and AD of the parahippocampal cingulum was stronger in female trauma survivors compared with male trauma survivors (B = 2.898 × 10⁻⁵, SE = 9.352 × 10⁻⁶, p = 0.002, FDR-corrected p = 0.032). Our results suggest that among ED patients with low rates of intracranial injuries observed on CT and MRI scans, acute peripheral levels of GFAP may be able to predict later disruption in structural connectivity.

Differentiation of levels of consciousness in patients with prolonged disorders of consciousness (DOC) remains a major challenge, especially differentiation between vegetative state (VS) and minimally conscious state (MCS). This study was to investigate the alterations of gut microbiota in patients with DOC and to identify potential microbiome biomarkers that can differentiate levels of consciousness. In this study, we collected fecal samples from patients with prolonged DOC, including 19 patients in MCS and 14 patients in VS; 16S-rRNA sequencing was used to investigate the gut microbiome of patients. Gut microbiota diversity, composition, and discriminant bacterial taxa were analyzed to identify potential biomarkers for differentiating levels of consciousness. We found that diversity and composition of gut microbiome were significantly altered in patients with DOC, and decreased alpha diversity was associated with lower levels of consciousness. Specific bacterial taxa including Firmicutes, Escherichia_shigella, Raecalibacterium, Lachnospiraceae, and Ruminococcaceae_UCG_013 were more abundant in patients in MCS, whereas Clostridiales were more abundant in patients in VS. In conclusion, the study results demonstrated that patients with DOC exhibited distinct diversity and composition of gut microbiota. And there was a decreasing trend of alpha diversity of gut microbiota from patients in MCS to patients in VS, which indicates that lower alpha diversity was associated with more severe level of unconsciousness. Specific bacterial taxa may be potential biomarkers to differentiate MCS and VS.

Whether and how traumatic brain injury (TBI) impacts ageing in the decades post-injury remains a matter of debate, partly due to a lack of controlled studies. This study examined the long-term impact of TBI on cognition and wellbeing in middle-aged and older adults and explored the relationship between age, cognition, and wellbeing, compared with a non-TBI control group. Cross-sectional data from 143 participants aged ≥40 with moderate-severe TBI (6–33 years post-injury; mean age 59.64) were compared with 71 non-TBI controls (mean age 62.10) group matched on age, gender, and premorbid IQ. Individuals with significant confounding comorbidities were excluded. A battery of neuropsychological tests and wellbeing measures (emotional distress, sleep, health-related quality of life [HRQoL]) was administered. Older age and TBI were each independently associated with poorer cognition across multiple domains (p < 0.05). The relationship between verbal learning and memory impairment post-TBI differed between age groups: individuals with TBI in their 40s–60s performed significantly worse than same-aged controls on verbal story acquisition (B = 0.09, p = 0.040, 95% confidence interval [CI] [0.004, 0.17]) and recall (B = 0.12, p = 0.009, 95% CI [0.03, 0.21]), and verbal wordlist recall (B = 0.11, p = 0.007, 95% CI [0.03, 0.19]). In comparison, no significant group differences in verbal memory emerged for ages 70–90. The TBI group reported greater emotional distress (B = 3.55, p < 0.001, 95% CI [1.73, 5.37]), poorer sleep quality (B = 1.07, p = 0.016, 95% CI [0.20, 1.94]), and poorer physical HRQoL (B = −4.26, p = 0.003, 95% CI [−7.08, −1.43]) than controls at all ages. Poorer physical HRQoL was related to poorer cognition post-TBI (p < 0.05). Our results challenge the notion that TBI exacerbates ageing. Moderate-severe TBI resulted in significant long-term impairments in cognition and wellbeing, with verbal learning and memory more impaired during middle-adulthood but not older adulthood compared to controls. TBI was not associated with changes to wellbeing with ageing. Intervention for verbal memory deficits in middle-aged adults with TBI is important, along with wider long-term supports for cognition, wellbeing, and activity participation in all individuals with TBI.

Traumatic brain injury with a Glasgow Coma Scale (GCS) score of 3–5 is characterized by severe injury, poor prognosis, and low survival rates. Deciding between aggressive neurosurgery and treatment discontinuation is challenging among older adults. This study analyzed the characteristics, treatment, and outcomes of acute subdural hematoma (ASDH) in older adults with a GCS score of 3–5 to assess the benefits of surgery and guide future treatment decisions. We analyzed the data of 205 older adults (aged 65 years or older) with ASDH and a GCS score of 3–5 registered in the Korean Neuro-Trauma Data Bank System from January 2018 to June 2021. The patients were divided into death and survival groups, and the demographic, clinical, and radiological characteristics; treatment methods; mortality rates; and treatment outcomes were analyzed, along with the relationship between variables and mortality. We also compared the Glasgow Outcome Scale–Extended (GOSE) scores and investigated whether surgical treatment affected mortality and good recovery rates according to age. According to the GOSE, 76.1% of patients died, 12.7% survived in a vegetative state, 3.9% had severe disabilities, and only 4.0% showed good recovery. The GCS score at admission was significantly associated with pupil reactivity; Rotterdam computed tomography score; time interval from injury to operation and arrival to operation; treatment; and hospital stay between patients who died and those who survived. Surgical treatment was significantly associated with a lower mortality rate but not with good recovery rates.

Traumatic brain injury (TBI) is a major global health concern, contributing substantially to mortality and disability. While previous studies have reported the global and regional burden of TBI, few have explored its long-term trends, cause-specific burden, sociodemographic disparities, and future projections in a comprehensive framework. To address this gap, we conducted a retrospective analysis using the Global Burden of Disease 2021 data to estimate TBI incidence, prevalence, and years lived with disability across sex, age, and Sociodemographic Index (SDI) quintiles. We used average annual percent change (AAPC) to evaluate temporal trends from 1990 to 2021 and applied Spearman’s correlation to examine the association between age-standardized incidence rate (ASIR) and SDI. Projections of future trends were made using an autoregressive integrated moving average model. The results revealed that global TBI cases increased from 17.0 million in 1990 to 20.8 million in 2021, although the global ASIR decreased from 324.43 to 259.02 per 100,000, with an AAPC of −0.80%. The age-standardized prevalence rate (ASPR) also declined in high SDI locations, from 539.7 to 425.9 per 100,000 (AAPC: −0.76%), with similar declines observed in high-middle SDI locations. Southern Sub-Saharan Africa showed the largest reductions, whereas Oceania experienced a slight increase in ASIR, largely driven by falls and road injuries, with notable gender-specific patterns. By 2031, TBI incidence rates are projected to decline for both sexes, with falls remaining stable and road injuries decreasing. While the ASIR and ASPR of TBI have decreased, the absolute number of cases has risen, underscoring the need for public health interventions that consider regional differences in TBI trends and causes in order to effectively reduce the burden.

Women with a history of intimate partner violence (IPV) are at risk for traumatic brain injury (TBI) with persistent neurobehavioral symptoms, post-traumatic stress disorder (PTSD), and chronic pain, which, together, characterize the polytrauma clinical triad. Among predominantly male Veteran samples, research has suggested that the triad may exacerbate health problems, compared with the presence of any component of the triad alone. The current study is the first to explore the polytrauma clinical triad among a sample of cisgender women who have experienced IPV (N = 198; M = 39.6 years old, SD = 11.9; 83.3% White, 7.1% Hispanic; 59.1% college-educated). Compared with participants without TBI history, participants with IPV-related TBI had higher rates of chronic pain (43.8% vs. 29.0%, p = 0.045, odds ratio [OR] = 1.87 [95% confidence interval: 1.01, 3.43]), PTSD with chronic pain (19.0% vs. 6.5%, p = 0.009, OR = 3.84 [1.41, 10.46]), neurobehavioral symptoms with chronic pain (40.0% vs. 22.6%, p = 0.030, OR = 2.01 [1.07, 3.79]), and the polytrauma clinical triad (19.0% vs. 6.5%, p = 0.009, OR = 3.84 [1.41, 10.46]), after adjusting for age and education. After controlling for IPV severity, however, there were no statistically significant group differences, suggesting that IPV severity may be closely linked to both risk of TBI and elevated symptomatology associated with the polytrauma clinical triad. Additionally, as the number of lifetime TBIs increased, the odds of having chronic pain (p = 0.011, OR = 1.17 [1.04, 1.33]) and chronic pain with concurrent neurobehavioral symptoms (p = 0.007, OR = 1.05 [1.05, 1.34]) also increased. These findings suggest that, especially when comorbid with IPV-related TBI, chronic pain may be a priority treatment target among individuals with a history of IPV. Considering that women with a history of IPV often experience concurrent health conditions, multicomponent interventions that address each condition within the polytrauma clinical triad may benefit this population.

Under-vehicle blast (UVB) caused by landmine detonation induces a distinct traumatic brain injury (TBI) and can be accompanied by head impact. Injured soldiers often undergo multiple flights after injury to access medical care and return to duty. Previous work has shown that low air pressure during air travel (hypobaria [HB]) exacerbates neurological injury, but the effects of one or more HB exposures on chronic brain injury are unknown. We hypothesized that multiple HB exposures after TBI would result in worse outcomes than 0–1 exposures. Sedated male ferrets underwent UVB and controlled cortical impact (CCI) under anesthesia (BCCI), followed by zero (normobaria [BCCI + NB]), one (BCCI + 1HB), or five (BCCI + 5HB) 6-h HB exposure(s) over 6 months post-injury or remained experimentally naïve. Anxiety-like behavior was assessed with the Open Field at 6 months post-injury. Ferrets also underwent T₂-weighted (T2w), resting-state functional magnetic resonance imaging, and diffusion-weighted imaging scans at pre-injury baseline and 6 months post-injury under anesthesia. Relative to naïve, BCCI + 5HB animals expressed significantly more anxiety-like behavior. Region of interest (ROI)-to-ROI functional connectivity (FC) analysis was conducted to evaluate FC changes within the anxiety network. ROI-based diffusion tensor and kurtosis imaging modeling was conducted to evaluate the white matter (WM) integrity of major anxiety-associated WM tracts. Results indicated increased FC between prefrontal cortex, amygdala, and hippocampus and decreased fractional anisotropy and mean kurtosis in cerebral WM, corpus callosum, cingulum, and fornix WM tracts when comparing BCCI + 5HB with all other groups. Together, these suggest that multiple HB exposures after BCCI exacerbate changes in neurological activity in the anxiety regulation brain network, as well as structural damage in the anxiety-associated WM tracts. Our findings demonstrate that air travel after TBI, particularly multiple flights, can have a chronic negative impact on brain structure and function.

Traumatic brain injury (TBI) disrupts the intestinal barrier, linking brain trauma to systemic inflammation and secondary complications. This study investigated the role of gut microbiota and its metabolites in intestinal barrier dysfunction following TBI, using a controlled cortical impact mouse model. TBI-induced gut dysbiosis was characterized by reduced microbial diversity and a loss of butyrate-producing bacteria, which led to decreased levels of short-chain fatty acids (SCFAs), particularly butyric acid. This disruption compromised the interleukin-22/regenerating islet-derived protein 3 (IL-22/Reg3) signaling pathway, which is essential for maintaining gut barrier integrity. Supplementation with Clostridium butyricum restored butyric acid production, enhanced IL-22/Reg3 expression, and alleviated TBI-induced intestinal permeability. These findings identify the SCFA/IL-22/Reg3 axis as a key mediator of gut barrier homeostasis after TBI and highlight the potential therapeutic role of butyrate-producing probiotics in managing TBI-associated intestinal complications.

Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with mild TBI (concussions) representing over 80% of cases. Although often considered benign, mild TBI is associated with persistent neuropsychiatric conditions, including post-traumatic stress disorder, anxiety, and depression. A hallmark of these conditions is impaired fear extinction (FE), the process by which learned fear responses are inhibited in safe contexts. This dysfunction contributes to maladaptive fear expression and is linked to altered neurocircuitry, particularly in the infralimbic cortex (IL), a key region in FE. Despite extensive evidence of impaired FE in patients with mild TBI and animal models, the specific mechanisms underlying this deficit remain poorly understood. This study aimed to address this gap by combining cued-FE behavior, local field potential recordings, and whole-cell patch-clamp techniques to investigate how mild TBI affects IL network activity and excitability in a mouse model of TBI. Our results demonstrate that mild lateral fluid percussion injury significantly impairs FE memory, as evidenced by an elevated cued-fear response during extinction testing 10 days post-injury. Field potential recordings revealed decreased activation of the IL network in both layers II/III and V, which was consistent with the observed behavioral deficits. Further analysis of synaptic physiology revealed an imbalance in excitatory and inhibitory neurotransmission (E/I imbalance) in the IL, characterized by reduced excitatory input and enhanced inhibitory input to neurons in both layers. Moreover, intrinsic excitability was altered in IL neurons after mild TBI. This study provides novel insights into how mild TBI disrupts the neurocircuitry underlying FE, specifically by suppressing IL excitability. These results highlight the importance of understanding the mechanistic disruptions in IL activity for developing therapeutic strategies to address fear-based disorders in patients with mild TBI.

Cerebrovascular autoregulation (CA) is a protective mechanism against brain injury. We present an ultrasound-based volumetric blood flow indices to monitor CA. Swine were instrumented under general anesthesia to monitor mean arterial blood pressure (MAP), intracranial pressure (ICP), and blood flow in the internal carotid artery (ICA) and femoral artery (FA) and flow velocity and volumetric flow in the middle cerebral artery (MCA) using transcranial Doppler. Animals were subjected to several physiological challenges to perturb cerebral pressure and flow hemodynamics as follows: (1) Vasopressor challenge by controlled infusion of norepinephrine to raise MAP to 150–160 mmHg, followed by its down titration. (2) Epidural hematoma by inflating a subdurally-placed balloon to raise ICP to 35–45 mmHg, followed by deflation of the balloon. (3) Hemorrhage and resuscitation by controlled removal of the blood from jugular vein. After a 10–15 min period of hypovolemia, resuscitated started to raise MAP to 65 mmHg. Pressure reactivity index (PRx) was calculated as a moving Pearson correlation coefficient between MAP and ICP. The flow/flow indices [FFx(s)] were calculated as a moving Pearson correlation coefficient between FA blood flow and one of the following (mean flow velocity in the MCA, relative volumetric flow in the MCA and blood flow in the ICA). FFx(s) were compared to PRx using area under the receiver operator characteristic curve (AUROC) and the precision recall curve (AUPRC). FFx(s) demonstrated AUPRC and AUROC ranges (0.88–0.91) and (0.73–0.79). The FFx(s) can act as excellent potential surrogates for the PRx for the assessments of CA.

The location close to the front lines of Mechnikov Hospital in the eastern Ukrainian city of Dnipro creates both opportunities and challenges. The same medical teams have worked closely together for years. They have learned how to provide the best possible care despite personnel shortages and overwhelming patient volumes, including many patients who are critically ill with systemic as well as neurological injuries. Outcomes are better than many might expect. International support and collaboration have been instrumental in achieving these good outcomes. Mechnikov Hospital neurosurgeons have developed new patient care pathways and management techniques that they disseminate internationally through publications and academic conferences. Prospective studies and other research activities are underway despite the obvious challenges caused by the war. The lessons learned by the team at Mechnikov Hospital will benefit other patients both now and in the future, especially as the international medical community prepares for possible large-scale combat operations in austere environments.