FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Implementation of activities of daily living retraining for individuals in post-traumatic amnesia.

Background Despite evidence of the efficacy of activities of daily living (ADL) retraining during post-traumatic amnesia (PTA) following traumatic brain injury (TBI), utilisation of this intervention in practice is unclear. Utilising an implementation science framework, the Consolidated Framework for Implementation Research, this study explored efforts to translate ADL retraining during PTA into the clinical practice of occupational therapists (OTs) working in TBI rehabilitation settings across Australia. Methods Participants were 44 OTs who attended a day-long training workshop that included knowledge and skill-based content regarding ADL retraining during PTA. Baseline and post-training ratings were completed including evaluation of workshop utility, and skill and knowledge-based competencies relevant to the intervention. Approximately 2 years later, nine trained OTs and two administrators were interviewed to explore the results of implementing the intervention. Results Overall, the training workshop was rated as being helpful and OT ratings of confidence (P P Conclusion Multiple barriers were identified in implementation of ADL retraining during PTA and require consideration to facilitate translation and promote best practice.

Long-Term Impact of Diffuse Traumatic Brain Injury on Neuroinflammation and Catecholaminergic Signaling: Potential Relevance for Parkinson's Disease Risk.

Traumatic brain injury (TBI) is associated with an increased risk of developing Parkinson's disease (PD), though the exact mechanisms remain unclear. TBI triggers acute neuroinflammation and catecholamine dysfunction post-injury, both implicated in PD pathophysiology. The long-term impact on these pathways following TBI, however, remains uncertain. In this study, male Sprague-Dawley rats underwent sham surgery or Marmarou's impact acceleration model to induce varying TBI severities: single mild TBI (mTBI), repetitive mild TBI (rmTBI), or moderate-severe TBI (msTBI). At 12 months post-injury, astrocyte reactivity (GFAP) and microglial levels (IBA1) were assessed in the striatum (STR), substantia nigra (SN), and prefrontal cortex (PFC) using immunohistochemistry. Key enzymes and receptors involved in catecholaminergic transmission were measured via Western blot within the same regions. Minimal changes in these markers were observed, regardless of initial injury severity. Following mTBI, elevated protein levels of dopamine D1 receptors (DRD1) were noted in the PFC, while msTBI resulted in increased alpha-2A adrenoceptors (ADRA2A) in the STR and decreased dopamine beta-hydroxylase (DßH) in the SN. Neuroinflammatory changes were subtle, with a reduced number of GFAP+ cells in the SN following msTBI. However, considering the potential for neurodegenerative outcomes to manifest decades after injury, longer post-injury intervals may be necessary to observe PD-relevant alterations within these systems.

[Traumatic damage to the diaphragm in children]. / Travmaticheskie povrezhdeniya diafragmy u detei.

OBJECTIVE: To analyze treatment outcomes in children with traumatic injuries of the diaphragm. MATERIAL AND METHODS: We followed-up 14 children aged 3-18 years with traumatic injuries of the diaphragm. Diagnostic measures included anamnesis, physical examination, pleural and abdominal puncture, bladder catheterization, ultrasound and X-ray examination including CT. RESULTS: Traumatic brain injury and thoracoabdominal trauma prevailed in children with traumatic injuries of the diaphragm. In 8 children, diaphragm injury was the result of a traffic accident. Of these, 5 ones died at the scene due to traumatic brain injury. In 3 children, diaphragm injury was associated with penetration of an iron pin through the perineum, pelvic cavity, abdominal and chest cavities when falling from a height (n=1) and sledding (n=2). Two children were littered with a pile of bricks and building materials. One girl suffered a diaphragm injury as a result of a stab wound. CONCLUSION: Combined damage to the diaphragm, TBI, chest and abdominal organs are serious injuries. Signs of shock, internal bleeding, respiratory failure and bone fractures come to the fore. Assistance to these children should be carried out in specialized hospitals.

Olfactory function after mild traumatic brain injury in children-a longitudinal case control study.

The prevalence of posttraumatic olfactory dysfunction in children after mild traumatic brain injury ranges from 3 to 58%, with potential factors influencing this variation, including traumatic brain injury severity and assessment methods. This prospective longitudinal study examines the association between mild traumatic brain injury and olfactory dysfunction in children. Seventy-five pediatric patients with mild traumatic brain injury and an age-matched healthy control group were enrolled. Olfactory function was assessed using the Sniffin' Sticks battery, which focuses on olfactory threshold and odor identification. The study found that children with mild traumatic brain injury had impaired olfactory function compared with healthy controls, particularly in olfactory threshold scores. The prevalence of olfactory dysfunction in the patient group was 33% and persisted for 1 yr. No significant association was found between traumatic brain injury symptoms (e.g. amnesia, loss of consciousness) and olfactory dysfunction. The study highlights the importance of assessing olfactory function in children after mild traumatic brain injury, given its potential impact on daily life. Although most olfactory dysfunction appears transient, long-term follow-up is essential to fully understand the recovery process. The findings add valuable insights to the limited literature on this topic and urge the inclusion of olfactory assessments in the management of pediatric mild traumatic brain injury.

Effects of Transcranial Direct Current Stimulation on Motor and Cognitive Dysfunction in an Experimental Traumatic Brain Injury Model.

AIM: To investigate the therapeutic and neuroprotective effects of transcranial direct current stimulation (tDCS) application on the traumatic brain injury (TBI)-induced glutamate and calcium excitotoxicity and loss of motor and cognitive functions. MATERIAL AND METHODS: Forty rats were equally divided in the sham, TBI, tDCS + TBI + tDCS, and TBI + tDCS groups. Mild TBI was induced by dropping a 450-g iron weight from a height of 1 m onto the skull of the rats. The tDCS + TBI + tDCS group was prophylactically administered 1 mA stimulation for 30 min for 7 days starting 5 days before inducing TBI. In the TBI + tDCS group, tDCS (1 mA for 30 min) was administered 2 h after TBI, on days 1 and 2. Cognitive and locomotor functions were assessed using the novel object recognition and open field tests. The calcium, glutamate, and N-methyl-D-aspartate receptor 1 (NMDAR1) levels in the hippocampus were measured using enzyme-linked immunosorbent assay. RESULTS: Although the motor and cognitive functions were substantially reduced in the TBI group when compared with the sham, they improved in the treatment groups (p < 0.05). The calcium, glutamate, and NMDAR1 levels were considerably higher in the TBI group than in the sham (p < 0.001). However, they were considerably lower in the tDCS + TBI + tDCS and TBI + tDCS groups than in the TBI groups (p < 0.05). In particular, the change in the tDCS + TBI + tDCS group was higher than that in the TBI + tDCS group. CONCLUSION: Application of tDCS before the development of TBI improved motor and cognitive dysfunction. It demonstrated a neuroprotective and therapeutic effect by reducing the excitotoxicity via the regulation of calcium and glutamate levels.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

BACKGROUND: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. METHODS: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. RESULTS: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. CONCLUSIONS: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

Association between mammillary body atrophy and memory impairment in retired athletes with a history of repetitive mild traumatic brain injury.

Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV-adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK-SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann-Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10-3, p < 0.001). The MBs volume/TBV ratio correlated with visual memory, as assessed, respectively, by the Rey-Osterrieth Complex Figure test delayed recall (ρ = 0.62, p < 0.001). In conclusion, retired athletes with rmTBI have MB atrophy, potentially contributing to memory impairment linked to the Papez circuit disconnection.

Lateral fluid percussion injury: A rat model of experimental traumatic brain injury.

Traumatic brain injury (TBI) represents one of the leading causes of disability and death worldwide. The annual economic impact of TBI-including direct and indirect costs-is high, particularly impacting low- and middle-income countries. Despite extensive research, a comprehensive understanding of the primary and secondary TBI pathophysiology, followed by the development of promising therapeutic approaches, remains limited. These fundamental caveats in knowledge have motivated the development of various experimental models to explore the molecular mechanisms underpinning the pathogenesis of TBI. In this context, the Lateral Fluid Percussion Injury (LFPI) model produces a brain injury that mimics most of the neurological and systemic aspects observed in human TBI. Moreover, its high reproducibility makes the LFPI model one of the most widely used rodent-based TBI models. In this chapter, we provide a detailed surgical protocol of the LFPI model used to induce TBI in adult Wistar rats. We further highlight the neuroscore test as a valuable tool for the evaluation of TBI-induced sensorimotor consequences and their severity in rats. Lastly, we briefly summarize the current knowledge on the pathological aspects and functional outcomes observed in the LFPI-induced TBI model in rodents.

The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review.

There is a growing body of evidence that suggests a connection between traumatic brain injury (TBI) and subsequent post-traumatic stress disorder (PTSD). While the exact mechanism is unknown, we hypothesize that chronic glutamate neurotoxicity may play a role. The consumption of dietary glutamate is a modifiable factor influencing glutamate levels in the blood and, therefore, in the brain. In this systematic review, we explored the relationship between dietary glutamate and the development of post-TBI PTSD. Of the 1748 articles identified, 44 met the inclusion criteria for analysis in this review. We observed that individuals from countries with diets traditionally high in glutamate had greater odds of developing PTSD after TBI (odds ratio = 15.2, 95% confidence interval 11.69 to 19.76, p < 0.01). These findings may support the hypothesis that chronically elevated blood glutamate concentrations caused by high dietary intake invoke neurodegeneration processes that could ultimately result in PTSD. Further studies will clarify whether lowering glutamate via diet would be an effective strategy in preventing or treating post-TBI PTSD.

Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.

BACKGROUND AND OBJECTIVES: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories. METHODS: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018. Plasma glial fibrillary acidic protein (GFAP), high-sensitivity C-reactive protein (hsCRP), S100b, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. The insomnia severity index was collected at 2 weeks, 3, 6, and 12 months postinjury. Participants were classified into insomnia trajectory classes based on a latent class model. We assessed the association of biomarkers with insomnia trajectories, controlling for medical and psychological comorbidities and demographics. RESULTS: Two thousand twenty-two individuals with TBI were studied. Elevations in D1 hsCRP were associated with persistent insomnia (severe, odds ratio [OR] = 1.33 [1.11, 1.59], p = 0.002; mild, OR = 1.10 [1.02, 1.19], p = 0.011). Similarly, D14 hsCRP elevations were associated with persistent insomnia (severe, OR = 1.27 [1.02, 1.59], p = 0.03). Of interest, D1 GFAP was lower in persistent severe insomnia (median [Q1, Q3]: 154 [19, 445] pg/mL) compared with resolving mild (491 [154, 1,423], p < 0.001) and persistent mild (344 [79, 1,287], p < 0.001). D14 GFAP was similarly lower in persistent (11.8 [6.4, 19.4], p = 0.001) and resolving (13.9 [10.3, 20.7], p = 0.011) severe insomnia compared with resolving mild (20.6 [12.4, 39.6]. Accordingly, increases in D1 GFAP were associated with reduced likelihood of having persistent severe (OR = 0.76 [95% CI 0.63-0.92], p = 0.004) and persistent mild (OR = 0.88 [0.81, 0.96], p = 0.003) compared with mild resolving insomnia. No differences were found with other biomarkers. DISCUSSION: Elevated plasma hsCRP and, surprisingly, lower GFAP were associated with adverse insomnia trajectories after TBI. Results support future prospective studies to examine their utility in guiding insomnia care after TBI. Further work is needed to explore potential mechanistic connections between GFAP levels and the adverse insomnia trajectories.

An effective insulin infusion protocol for severe traumatic brain injury patients: A retrospective observational study.

PURPOSE: Severe traumatic brain injury (sTBI) patients often experience stress hyperglycaemia, which can lead to negative outcomes. This study aims to introduce an effective insulin infusion protocol specifically designed for sTBI patients. METHODS: Data was collected from all sTBI patients during two periods: 1 October 2019 to 30 April 2020, and 1 June 2020 to 31 December 2020. In May 2020, a new insulin infusion protocol was implemented. Blood glucose management, infection, coagulation, and prognosis were compared in these two periods. RESULT: 195 patients were included, with 106 using the new protocol. The proportion of hyperglycaemia decreased from 40.04% to 26.91% (P<0.05), and the proportion of on-target blood glucose levels increased from 35.69% to 38.98% (P<0.05). Average blood glucose levels decreased from 9.98±2.79mmol/L to 8.96±2.82mmol/L (P<0.05). There was no substantial increase in hypoglycaemia, which remained controlled below 1%. The new protocol positively influenced glucose concentration and dispersion trends. There were no significant differences in catheter-related infections, antibiotic use, mechanical ventilation (MV) duration, length of stay in ICU, Glasgow Outcome Scale (GOS), or mortality. However, the conventional protocol group had a higher coagulation tendency (R-value of thromboelastography 4.80±1.35min vs. 5.52±1.87min, P<0.05), with no difference in deep vein thrombosis (DVT) incidence. CONCLUSION: Our findings suggest that a customized insulin infusion process for sTBI patients can effectively manage blood glucose. While there is no significant improvement in infection control or prognosis, it may have a positive impact on coagulation without affecting the occurrence of DVT.

The combination treatment of hypothermia and intranasal insulin ameliorates the structural and functional changes in a rat model of traumatic brain injury.

The present study aimed to investigate the combination effects of hypothermia (HT) and intranasal insulin (INS) on structural changes of the hippocampus and cognitive impairments in the traumatic brain injury (TBI) rat model. The rats were divided randomly into the following five groups (n = 10): Sham, TBI, TBI with HT treatment for 3 h (TBI + HT), TBI with INS (ten microliters of insulin) treatment daily for 7 days (TBI + INS), and TBI with combining HT and INS (TBI + HT + INS). At the end of the 7th day, the open field and the Morris water maze tests were done for evaluation of anxiety-like behavior and memory performance. Then, after sacrificing, the brain was removed for stereological study. TBI led to an increase in the total volume of hippocampal subfields CA1 and DG and a decrease in the total number of neurons and non-neuronal cells in both sub-regions, which was associated with anxiety-like behavior and memory impairment. Although, the combination of HT and INS prevented the increased hippocampal volume and cell loss and improved behavioral performances in the TBI group. Our study suggests that the combined treatment of HT and INS could prevent increased hippocampal volume and cell loss in CA1 and DG sub-regions and consequently improve anxiety-like behaviors and memory impairment following TBI.

Impact of PTSD treatment on postconcussive symptoms in veterans: A comparison of sertraline, prolonged exposure, and their combination.

Many Veterans who served in Iraq and Afghanistan struggle with posttraumatic stress disorder (PTSD) and the effects of traumatic brain injuries (TBI). Some people with a history of TBI report a constellation of somatic, cognitive, and emotional complaints that are often referred to as postconcussive symptoms (PCS). Research suggests these symptoms may not be specific to TBI. This study examined the impact of PTSD treatment on PCS in combat Veterans seeking treatment for PTSD. As part of a larger randomized control trial, 198 Operation Iraqi Freedom, Operation Enduring Freedom, Operation New Dawn (OIF/OEF/OND) Veterans with PTSD received Prolonged Exposure Therapy, sertraline, or the combination. Potential deployment related TBI, PCS, PTSD and depression symptoms were assessed throughout treatment. Linear mixed models were used to predict PCS change over time across the full sample and treatment arms, and the association of change in PTSD and depression symptoms on PCS was also examined. Patterns of change for the full sample and the subsample of those who reported a head injury were examined. Results showed that PCS decreased with treatment. There were no significant differences across treatments. No significant differences were found in the pattern of symptom change based on TBI screening status. Shifts in PCS were predicted by change PTSD and depression. Results suggest that PCS reduced with PTSD treatment in this population and are related to shift in depression and PTSD severity, further supporting that reported PCS symptoms may be better understood as non-specific symptoms.

Traumatic Brain Injury and Post-Traumatic Stress Disorder and Their Influence on Development and Pattern of Alzheimer's Disease Pathology in Later Life.

Background: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are potential risk factors for the development of dementia including Alzheimer's disease (AD) in later life. The findings of studies investigating this question are inconsistent though. Objective: To investigate if these inconsistencies are caused by the existence of subgroups with different vulnerability for AD pathology and if these subgroups are characterized by atypical tau load/atrophy pattern. Methods: The MRI and PET data of 89 subjects with or without previous TBI and/or PTSD from the DoD ADNI database were used to calculate an age-corrected gray matter tau mismatch metric (ageN-T mismatch-score and matrix) for each subject. This metric provides a measure to what degree regional tau accumulation drives regional gray matter atrophy (matrix) and can be used to calculate a summary score (score) reflecting the severity of AD pathology in an individual. Results: The ageN-T mismatch summary score was positively correlated with whole brain beta-amyloid load and general cognitive function but not with PTSD or TBI severity. Hierarchical cluster analysis identified five different spatial patterns of tau-gray matter interactions. These clusters reflected the different stages of the typical AD tau progression pattern. None was exclusively associated with PTSD and/or TBI. Conclusions: These findings suggest that a) although subsets of patients with PTSD and/or TBI develop AD-pathology, a history of TBI or PTSD alone or both is not associated with a significantly higher risk to develop AD pathology in later life. b) remote TBI or PTSD do not modify the typical AD pathology distribution pattern.

Influence of affective instability on suicidal ideation beyond traumatic brain injury and posttraumatic stress disorder in veterans.

OBJECTIVE: Mild traumatic brain injury (TBI) is associated with long-term consequences, including greater risk for posttraumatic stress disorder (PTSD) and suicidal ideation. Affective instability is also independently related to PTSD and suicidality, which may explain why some individuals continue to experience chronic psychiatric complaints following mild TBI. The purpose of the present study was to evaluate affective instability as a key factor for PTSD and suicidal ideation among Veterans with and without TBI. METHOD: Participants (N = 299 Veterans; 86.96% male) completed the Personality Assessment Inventory (PAI) and structured clinical interviews for TBI and psychiatric diagnoses. Hierarchical linear regression was used to evaluate main and interaction effects. RESULTS: There were no significant differences in affective instability (p = 0.140) or suicidal ideation (p = 0.453) between Veterans with or without TBI. Individuals with TBI were more likely to have a PTSD diagnosis (p = 0.001). Analyses evaluating PTSD diagnosis as an outcome indicated a main effect of affective instability (p < 0.001), but not TBI (p = 0.619). Analyses evaluating suicidal ideation as an outcome demonstrated an interaction effect between PTSD and affective instability beyond the effects of TBI (p = 0.034). CONCLUSIONS: Severe Affective instability appears to be a key factor in suicidal ideation among Veterans beyond TBI or PTSD history. PTSD was more strongly associated with suicidality at lower and moderate levels of affective instability. At severe levels of affective instability, however, Veterans with and without PTSD experienced suicidal ideation at similar rates. Findings suggests that high levels of affective instability not better explained by other psychiatric conditions confers similar suicidality risk to that of PTSD in a Veteran population.

Bilateral vertebral artery injury leads to brain death following traumatic brain injury: a case report.

BACKGROUND: Vertebral artery injury is a rare condition in trauma settings. In the advanced stages, it causes death. CASE: A 31-year-old Sundanese woman with cerebral edema, C2-C3 anterolisthesis, and Le Fort III fracture after a motorcycle accident was admitted to the emergency room. On the fifth day, she underwent arch bar maxillomandibular application and debridement in general anesthesia with a hyperextended neck position. Unfortunately, her rigid neck collar was removed in the high care unit before surgery. Her condition deteriorated 72 hours after surgery. Digital subtraction angiography revealed a grade 5 bilateral vertebral artery injury due to cervical spine displacement and a grade 4 left internal carotid artery injury with a carotid cavernous fistula (CCF). The patient was declared brain death as not improved cerebral perfusion after CCF coiling. CONCLUSIONS: Brain death due to cerebral hypoperfusion following cerebrovascular injury in this patient could be prevented by early endovascular intervention and cervical immobilisation.