Effects Of Traumatic Brain Injury Research Articles

Predictive capability of Cys112Arg single nucleotide polymorphisms of the apolipoprotein E gene in assessing the risk of immediate and early post-traumatic seizures

This study is aimed at investigating epileptic seizures, one of the consequences of traumatic brain injury (TBI). Immediate and early post-traumatic seizures, as well as late post-traumatic epileptic seizures or post-traumatic epilepsy, can have different pathogenetic bases. The following key risk factors associated with post-traumatic epilepsy are known: duration of unconsciousness, gunshot wounds, intracranial hemorrhage, diffuse axonal injury, prolonged (more than 3 days) post-traumatic amnesia, acute subdural hematoma with surgical evacuation, immediate and early post-traumatic epileptic seizures, fracture of the skull bones. The role of genetic factors in post-traumatic seizures is poorly understood due to the complexity and multiple causal mechanisms. This paper addresses the role of genetic factors in the occurrence and severity of epileptic events in patients with TBI. In particular, we investigated the role of the Cys112Arg single nucleotide polymorphism of the apolipoprotein E gene. Apolipoprotein E is known for its role in the transport and metabolism of lipids and, therefore, the development of cardiovascular diseases; it is also associated with Alzheimer's disease and has recently been studied in the context of association with epilepsy. The study shows an association between this polymorphism and the risk of immediate and early epileptic seizures in patients with severe TBI.

Exercise as a behavioral approach to improve mood in persons with traumatic brain injury.

Mood disturbance is a common, long-term, negative consequence of traumatic brain injury (TBI) that is insufficiently addressed by most traditional treatment modalities. A large body of evidence supports the efficacy of exercise training (ET) to broadly improve mood, as measured most often by the Profile of Mood States (POMS). However, this behavioral approach is not used nearly enough in the TBI population, and when it is, mood is rarely measured. This scoping review will evaluate the use of POMS as a mood measure in TBI research and to establish a rationale for using ET as a behavioral approach to broadly improve mood in persons with TBI.

“Nobody Has a Caseload Called, Patients With Traumatic Brain Injury ”: Rationale to Include TBI Content Into Audiology Programs

Purpose: Understanding the wide-ranging effects of traumatic brain injury (TBI), including posttraumatic auditory and vestibular disturbances, is an essential part of shaping audiology students' readiness for clinical practice. Several recent audiology studies revealed discrepancies in knowledge and application among practicing audiologists in Australia concerning TBI. These studies emphasize the need of exploring the existing TBI-related curriculum within Australian graduate audiology programs. Method: A qualitative research design employing semistructured interviews was conducted. A total of six leading academic educators from all six Australian graduate audiology programs participated in the study. Interview transcripts were analyzed using thematic analysis. Results: Implementation of TBI content into audiological curricula was found to be influenced by three interrelated themes: professional culture, contextual barriers, and practice of teaching and learning. Conclusions: The findings provide an insight into the perceived barriers associated with incorporating TBI-related content into existing audiology curricula. The findings highlight the importance of enhancing audiology curricula in relation to TBI, ensuring that graduate audiologists can provide high-quality care and management for patients with posttraumatic audiovestibular disturbances.

Multiplexed Quantitative Proteomics Reveals Proteomic Alterations in Two Rodent Traumatic Brain Injury Models.

In many cases of traumatic brain injury (TBI), conspicuous abnormalities, such as scalp wounds and intracranial hemorrhages, abate over time. However, many unnoticeable symptoms, including cognitive, emotional, and behavioral dysfunction, often last from several weeks to years after trauma, even for mild injuries. Moreover, the cause of such persistence of symptoms has not been examined extensively. Recent studies have implicated the dysregulation of the molecular system in the injured brain, necessitating an in-depth analysis of the proteome and signaling pathways that mediate the consequences of TBI. Thus, in this study, the brain proteomes of two TBI models were examined by quantitative proteomics during the recovery period to determine the molecular mechanisms of TBI. Our results show that the proteomes in both TBI models undergo distinct changes. A bioinformatics analysis demonstrated robust activation and inhibition of signaling pathways and core proteins that mediate biological processes after brain injury. These findings can help determine the molecular mechanisms that underlie the persistent effects of TBI and identify novel targets for drug interventions.

TIMP2 ameliorates blood-brain barrier disruption in traumatic brain injury by inhibiting Src-dependent VE-cadherin internalization.

Blood-brain barrier (BBB) disruption is a serious pathological consequence of traumatic brain injury (TBI), for which there are limited therapeutic strategies. Tissue inhibitor of metalloproteinase-2 (TIMP2), a molecule with dual functions of inhibiting MMP activity and displaying cytokine-like activity through receptor binding, has been reported to inhibit VEGF-induced vascular hyperpermeability. Here, we investigate the ability of TIMP2 to ameliorate BBB disruption in TBI and the underlying molecular mechanisms. Both TIMP2 and AlaTIMP2, a TIMP2 mutant without MMP-inhibiting activity, attenuated neurological deficits and BBB leakage in TBI mice; they also inhibited junctional protein degradation and translocation to reduce paracellular permeability in human brain microvascular endothelial cells (ECs) exposed to hypoxic plus inflammatory insult. Mechanistic studies revealed that TIMP2 interacted with α3β1 integrin on ECs, inhibiting Src activation-dependent VE-cadherin phosphorylation, VE-cadherin/catenin complex destabilization, and subsequent VE-cadherin internalization. Notably, localization of VE-cadherin on the membrane was critical for TIMP2-mediated EC barrier integrity. Furthermore, TIMP2-mediated increased membrane localization of VE-cadherin enhanced the level of active Rac1, thereby inhibiting stress fiber formation. All together, our studies have identified an MMP-independent mechanism by which TIMP2 regulates EC barrier integrity after TBI. TIMP2 may be a therapeutic agent for TBI and other neurological disorders involving BBB breakdown.

Non-Invasive Systems Application in Traumatic Brain Injury Rehabilitation.

Traumatic brain injury (TBI) is a significant public health concern, often leading to long-lasting impairments in cognitive, motor and sensory functions. The rapid development of non-invasive systems has revolutionized the field of TBI rehabilitation by offering modern and effective interventions. This narrative review explores the application of non-invasive technologies, including electroencephalography (EEG), quantitative electroencephalography (qEEG), brain-computer interface (BCI), eye tracking, near-infrared spectroscopy (NIRS), functional near-infrared spectroscopy (fNIRS), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) in assessing TBI consequences, and repetitive transcranial magnetic stimulation (rTMS), low-level laser therapy (LLLT), neurofeedback, transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS) and virtual reality (VR) as therapeutic approaches for TBI rehabilitation. In pursuit of advancing TBI rehabilitation, this narrative review highlights the promising potential of non-invasive technologies. We emphasize the need for future research and clinical trials to elucidate their mechanisms of action, refine treatment protocols, and ensure their widespread adoption in TBI rehabilitation settings.

Emotional state of patients with mild traumatic brain injury

Introduction and Aim: Psychological effects of traumatic brain injury (TBI) are frequently present in addition to neurological deficits. The purpose of this study is to assess the emotional state of patients with mild TBI in the remote period. Methods: This study included 78 patients aged 22–53 years with a reliably established diagnosis of mild TBI, with damage duration ranging from 1–5 years. The mean age was (34.6±3.2 years). To determine the level of anxiety, the Taylor Manifest Anxiety Scale was used. Results: The testing revealed that patients with suicidal thoughts had a significantly higher level of anxiety (34.2%) than the patients with TBI in the main group (27.5%). Comparative analysis between the two groups showed that the uselessness was more characteristic for suicides (22.8±0.14), who considered themselves completely useless than patients with TBI (20.6±1.36) with reliability (t = 4.2; p<0.001). Conclusion: Due to the damage that post-traumatic stress disorder (PTSD) can do to the body, especially to mental health, it is important to use medical and psychosocial rehabilitation as early as possible in the treatment stage to figure out the type and severity of the psychoemotional disorder and correct the psychosomatic state using psychopharmacological and psychotherapeutic effects.

Sex-Specific and Traumatic Brain Injury Effects on Dopamine Receptor Expression in the Hippocampus.

Traumatic brain injury (TBI) is a major health concern. Each year, over 50 million individuals worldwide suffer from TBI, and this leads to a number of acute and chronic health issues. These include affective and cognitive impairment, as well as an increased risk of alcohol and drug use. The dopaminergic system, a key component of reward circuitry, has been linked to alcohol and other substance use disorders, and previous research indicates that TBI can induce plasticity within this system. Understanding how TBI modifies the dopaminergic system may offer insights into the heightened substance use and reward-seeking behavior following TBI. The hippocampus, a critical component of the reward circuit, is responsible for encoding and integrating the spatial and salient aspects of rewarding stimuli. This study explored TBI-related changes in neuronal D2 receptor expression within the hippocampus, examining the hypothesis that sex differences exist in both baseline hippocampal D2 receptor expression and its response to TBI. Utilizing D2-expressing tdTomato transgenic male and female mice, we implemented either a sham injury or the lateral fluid percussion injury (FPI) model of TBI and subsequently performed a region-specific quantification of D2 expression in the hippocampus. The results show that male mice exhibit higher baseline hippocampal D2 expression compared to female mice. Additionally, there was a significant interaction effect between sex and injury on the expression of D2 in the hippocampus, particularly in regions of the dentate gyrus. Furthermore, TBI led to significant reductions in hippocampal D2 expression in male mice, while female mice remained mostly unaffected. These results suggest that hippocampal D2 expression varies between male and female mice, with the female dopaminergic system demonstrating less susceptibility to TBI-induced plasticity.

Behavioral, Genomic and Neurochemical Deficits Evoked by Neurotrauma in Adult Zebrafish (<i>Danio rerio</i>)

Traumatic brain injury (TBI) is a serious biomedical problem with high prevalence and mortality risks. Understanding TBI in traditional (e.g., rodent) animal models often presents challenges due to the complexity of their brain and its limited regenerative capabilities. Here, we present novel data obtained using the zebrafish TBI model based on a stab wound of telencephalon, aiming to investigate behavioral and molecular consequences of TBI in zebrafish. Four days following the injury, adult zebrafish displayed hypolocomotion in the novel seen tank test and impaired working memory in the Y-maze test, paralleling behavioral deficits in rodent models and human TBI patients. Molecular analyses of key genes involved in the inflammatory response and cell death pathways revealed a remarkable upregulation of the interferon-stimulated gene 15 (isg15) in the injured telencephalon, a general biomarker for neuronal damage. Furthermore, noradrenaline (but not dopamine or serotonin) levels in whole-brain tissue declined following TBI, likely contributing to the observed cognitive deficits and implicating neurotransmitter dysregulation in TBI pathogenesis.

The neuropathology of intimate partner violence

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd–8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd–9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Gender versus sex in predicting outcomes of traumatic brain injury: a cohort study utilizing large administrative databases

Understanding the factors associated with elevated risks and adverse consequences of traumatic brain injury (TBI) is an integral part of developing preventive measures for TBI. Brain injury outcomes differ based on one’s sex (biological characteristics) and gender (social characteristics reflecting norms and relationships), however, whether it is sex or gender that drives differences in early (30-day) mortality and discharge location post-TBI is not well understood. In the absence of a gender variable in existing data, we developed a method for “measuring gender” in 276,812 residents of Ontario, Canada who entered the emergency department and acute care hospitals with a TBI diagnostic code between April 1st, 2002, and March 31st, 2020. We applied logistic regression to analyse differences in diagnostic codes between the sexes and to derive a gender score that reflected social dimensions. We used the derived gender score along with a sex variable to demonstrate how it can be used to separate the relationship between sex, gender and TBI outcomes after severe TBI. Sex had a significant effect on early mortality after severe TBI with a rate ratio (95% confidence interval (CI)) of 1.54 (1.24–1.91). Gender had a more significant effect than sex on discharge location. A person expressing more “woman-like” characteristics had lower odds of being discharged to rehabilitation versus home with odds ratio (95% CI) of 0.54 (0.32–0.88). The method we propose offers an opportunity to measure a gender effect independently of sex on TBI outcomes.

Updates on Improving Imaging Modalities for Traumatic Brain Injury.

The Center for Disease Control and Prevention reports that traumatic brain injury (TBI) was related to over 64,000 deaths in the United States in 2020, equating to more than 611 TBI-related hospitalizations and 176 TBI-related deaths per day. There are both long- and short-term sequelae involved with the pathophysiology of TBI that can range from mild to severe. Recently, more effort has been devoted to understanding the long-term consequences of TBI and how early detection of these injuries can prevent late clinical manifestations. Obtaining proper, detailed imaging is key to guiding the direction of intervention, but there is a gap in the understanding of how TBI imaging can be used to predict and prevent the long-term morbidities seen with even mild forms of TBI. There have been significant strides in the advancement of TBI imaging that allows for quicker, more affordable, and more effective imaging of intracranial bleeds, axonal injury, tissue damage, and more. Despite this, there is still room for improved standardization and more data supporting the justification of using certain imaging modalities. This review aims to outline recent advancements in TBI imaging and areas that require further investigation to improve patient outcomes and minimize the acute and chronic comorbidities associated with TBI.

Association between steroid use and concussions among high school athletes: a cross-sectional analysis of the Youth Risk Behavior Surveillance System.

In 2017, there were almost 2.5 million high school students who experienced a concussion while playing a sport, raising concern for the neurologic problems that theycould face. Some of these athletes may seek to gain a competitive advantage in their sport by utilizing substances like steroids. However, steroid use can cause increased aggression and body mass index (BMI), which might lead to heightened risk for concussions. Despite extensive research, we found no previous evidence linking these two factors. This analysis aims to investigate steroid use trends in high school athletes and to determine whether there is an association between steroid use and concussions in these athletes. We conducted a cross-sectional analysis of the cumulative Youth Risk Behavior Surveillance System (YRBSS). Respondents were added if they participated in sports and answered the steroid and concussion prompts. Demographic variables were assessed including age, grade, BMI, gender, and race/ethnicity. We found that 3.7 % (n=2991) of high school athletes reported previous steroid use and that 20.7 % (n=2273) reported having sustained a concussion. There was a statistically significant difference in steroid use by race/ethnicity (p<0.001), with the highest rate of use (7.2 %) among American Indian/Alaska Natives (AI/AN). A significantly higher prevalence of steroid use occurred in athletes who were males (4.7 %) than females (2.5 %) and inathletes with a BMI>95 % (5.2 %) compared with those with a BMI between 85 and 95 % (3.9 %) and <85 % (3.5 %) (χ2=135.1, p<0.001 and χ2=16.3, p<0.001, respectively). Further, our results showed that the prevalence of steroid use among high school athletes decreased from 3.4 % in 1999 to 1.9 % in 2019, with the most drastic drop occurring between 2015 and 2019-declining 1.9 %. Whereas 19.6 % of athletes reported a concussion without steroid use, 54.6 % of steroid-utilizing athletes reported having experienced a concussion-a statistically significant finding (adjusted odds ratio [AOR]=4.3; 95 % CI: 3.2-5.9). Finally, compared with White athletes, we found that AI/AN athletes were significantly more likely to have sustained a concussion (AOR=2.3; 95 % CI=1.2-4.3). Although our study found decreasing rates of steroid use among high school athletes from 1999 through 2019, our results also show that steroid use is significantly associated with sustaining a concussion. Additionally, the data from YRBSS also demonstrates that AI/AN high school athletes are more likely to utilize steroids and sustain a concussion. Given the long-term consequences of traumatic brain injuries, we recommend that coaches should be aware of potential steroid use among players, and that coaches, athletic trainers, and physicians should all be aware of concussion protocols and remove players from games for evaluation when a concussion is suspected.

Long-Term Follow-Up of Critically Ill Patients With Traumatic Brain Injury: From Intensive Care Parameters to Patient and Caregiver-Reported Outcome.

Abstract Traumatic brain injury (TBI) is associated with a high social and financial burden due to persisting (severe) disabilities. The consequences of TBI after intensive care unit (ICU) admission are generally measured with global disability screeners such as the Glasgow Outcome Scale-Extended (GOSE), which may lack precision. To improve outcome measurement after brain injury, a comprehensive clinical outcome assessment tool called the Minimal Dataset for Acquired Brain Injury (MDS-ABI) was recently developed. The MDS-ABI covers 12 life domains (demographics, injury characteristics, comorbidity, cognitive functioning, emotional functioning, energy, mobility, self-care, communication, participation, social support, and quality of life), as well as informal caregiver capacity and strain. In this cross-sectional study, we used the MDS-ABI among formerly ICU admitted patients with TBI to explore the relationship between dichotomized severity of TBI and long-term outcome. Our objectives were to: 1) summarize demographics, clinical characteristics, and long-term outcomes of patients and their informal caregivers, and 2) compare differences between long-term outcomes in patients with mild-moderate TBI and severe TBI based on Glasgow Coma Scale (GCS) scores at admission. Participants were former patients of a Dutch university hospital (total n = 52; mild-moderate TBI n = 23; severe TBI n = 29) and their informal caregivers (n = 45). Hospital records were evaluated, and the MDS-ABI was administered during a home visit. On average 3.2 years after their TBI, 62% of the patients were cognitively impaired, 62% reported elevated fatigue, and 69% experienced restrictions in ≥2 participation domains (most frequently work or education and going out). Informal caregivers generally felt competent to provide necessary care (81%), but 31% experienced a disproportionate caregiver burden. All but four patients lived at home independently, often together with their informal caregiver (81%). Although the mild-moderate TBI group and the severe TBI group had significantly different clinical trajectories, there were no persisting differences between the groups for patient or caregiver outcomes at follow-up. As a large proportion of the patients experienced long-lasting consequences beyond global disability or independent living, clinicians should implement a multi-domain outcome set such as the MDS-AB to follow up on their patients.

Anacardic acid improves neurological deficits in traumatic brain injury by anti-ferroptosis and anti-inflammation

BackgroundTraumatic brain injury (TBI) is an important cause of disability and death. TBI leads to multiple forms of nerve cell death including ferroptosis due to iron-dependent lipid peroxidation. Anacardic acid (AA) is a natural component extracted from cashew nut shells, which has been reported to have neuroprotective effects in traumatic brain injury. We investigated whether AA has an anti-ferroptosis effect in TBI. MethodsWe used the Feeney free-fall impact method to construct a TBI model to investigate the effect of AA on ferroptosis caused by TBI, in which Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, served as a positive control group. We first identified the therapeutic effect of AA on TBI through modified neurological severity score (mNSS) and determined the appropriate concentration. Secondly, we investigated the effect of AA on the expression level of the key protein of ferroptosis by Western blotting and immunohistochemistry. Then the effect of AA on nerve tissue injury and nerve function improvement was verified. Finally, enzym-linked immunosorbent assay (ELISA) was used to verify that AA could reduce inflammation after TBI. ResultsWe found the intensely inhibitory effect of AA on ferroptosis, which is in parallel with the results obtained after Fer-1 treatment. In addition, AA and Fer-1 mitigated TBI-mediated tissue defects, destruction of the blood-brain barrier, and neurodegeneration. Novel object recognition (NOR), mNSS and water maze test showed that AA could significantly reduce the impairment of neural function and behavioral cognitive ability caused by TBI. Finally, we also demonstrated that AA has not only an anti-ferroptosis effect, but also an anti-inflammation effect. ConclusionsAA can reduce the neurological impairment and behavioral cognitive impairment caused by TBI through the dual effect of anti-ferroptosis and anti-inflammation.

B - 99 The Effects of Traumatic Brain Injury on Empathy and Quality of Life.

The focus of this present research was to investigate the relationship between empathy and quality of life in individuals with moderate-to-severe TBI. Individuals with moderate-to-severe TBI between ages 18 and 65 (N&#3f39) completed the Quality of Life after Brain Injury (QOLIBRI) and Empathy Quotient (EQ). Performance on the EQ was correlated with QOLIBRI (r(1,37) = 0.398, p = 0.012). Based on their EQ scores, the participants were divided into three groups: below-average empathy (N = 9), average empathy (N = 16), and above average empathy (N = 14). There was a statistically significant difference in the total QOLIBRI scores across the three empathy groups (F (2, 36) = 5.037, p = 0.012). Post-hoc analysis, indicated those with lower EQ scores also reported lower QOLIBRI scores. This work provides evidence that those with low empathy may have a worse quality of life after brain injury relative to those with higher levels of empathy. Understanding the relationship between empathy and quality of life for individuals with brain injury can inform professionals where to target interventions such that improvements in empathy may also increase quality of life.

A - 133 Self-Reported Loss of Consciousness Predicts Executive Functions in Veterans with a History of Traumatic Brain Injury.

The long-term cognitive effects of traumatic brain injury (TBI) in military personnel remain unclear and need to be better understood. We assessed how cognitive performance was related to the remote history of TBI involving loss of consciousness (LOC) and blast injury (regardless of LOC) in veterans. Veterans (N = 101; age 42.8 ± 10.5years; 10 Females) with a self-reported history of TBI and persistent cognitive symptoms were recruited. Effects of (1) the presence of LOC, (2) total number of TBIs with LOC (0, 1-2, >2), and (3) the presence of blast injury were examined on composite scores from tests of executive function (Trail-Making Test B, Color Word Interference), word retrieval (Boston Naming, Letter and Category Fluency), processing speed (Trail Making-A, Color Word Naming/Reading), and episodic memory (Rey-Auditory Verbal Learning Test-total learning and delayed recall), while controlling for age, sex, years of education, and total number of TBIs. TBI with LOC was a significant predictor of executive function (p = 0.014) and processing speed (p = 0.014), with more episodes of LOC predicting lower functioning, but not of word retrieval or episodic memory (p > 0.1). Additionally, presence of a blast injury, regardless of LOC, did not predict differences in function on any of the composite measures. Self-reported TBI history with LOC was associated with poorer executive function and processing speed. The findings further characterize the relationship between TBI history and long-term cognitive sequelae in veterans, particularly suggesting LOC can affect neural systems underlying executive function and processing speed.

Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood–brain barrier integrity

Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional EphA4f/f/Tie2-Cre and EphA4f/f/VE-Cadherin-CreERT2 knockout (KO) mice promotes blood-brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury. scRNAseq of capillary-derived KO ECs showed increased differential gene expression of BBB-related junctional and actin cytoskeletal regulators, namely, A-kinase anchor protein 12, Akap12, whose presence at Tie2 clustering domains is enhanced in KO microvessels. Transcript and protein analysis of CCI-injured whole cortical tissue or cortical-derived ECs suggests that EphA4 limits the expression of Cldn5, Akt, and Akap12 and promotes Ang2. Blocking Tie2 using sTie2-Fc attenuated protection and reversed Akap12 mRNA and protein levels cortical-derived ECs. Direct stimulation of Tie2 using Vasculotide, angiopoietin-1 memetic peptide, phenocopied the neuroprotection. Finally, we report a noteworthy rise in soluble Ang2 in the sera of individuals with acute TBI, highlighting its promising role as a vascular biomarker for early detection of BBB disruption. These findings describe a contribution of the axon guidance molecule, EphA4, in mediating TBI microvascular dysfunction through negative regulation of Tie2/Akap12 signaling.

SAT270 Parity Increases Corticosterone Response To Restraint-induced Stress After Mild Blast Traumatic Brain Injury In Mice

Abstract Disclosure: S. Anisowicz: None. M. Bodemeier Loayza Careaga: None. T. Wu: None. Background: Traumatic brain injury (TBI) is a common problem worldwide, with an estimated incidence of 69 million injuries per year. In the US military, one of the most common forms of TBI during operational deployments after Sep 11, 2001 was the blast TBI, thought to be responsible for over 80% of TBI sustained in theater. One consequence of TBI is dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. HPA axis dysregulation is linked to increased risk for psychiatric disorders. Furthermore, prior research has shown that TBI may dysregulate the HPA axis in a sex-dependent manner. Throughout a female’s life span, there are several sentinel events of hormonal consequence, including pubarche, menopause, and parity, which are known to be times of changes in risks for psychiatric disorders. Objectives: The role of parity on TBI response has not yet been studied, though parity has been shown to decrease fear-related behaviors and decreased corticosterone load in multiparous mice when compared to nulliparous (NP) controls. Our objective is to determine if parity alters corticosterone (CORT) response to restraint, a mild psychological stressor, in mice exposed to mild blast TBI (mbTBI). Methods: One hundred thirteen NP or primiparous (PP) C57Bl6/J mice were randomly assigned to receive sham or mbTBI. Among those that received mbTBI (19.2 ± 0.12 psi), 32 were NP and 24 were PP. Among sham mice, 32 were NP and 26 were PP. All mice received isoflurane anesthesia prior to sham or mbTBI treatment. At 7-8 days after mbTBI, half the mice within each treatment group were subjected to a mild 20-min restraint before being anesthetized by CO2 followed by collection of trunk blood. Serum was harvested and analyzed for CORT concentrations by ELISA (Enzo Life Sciences). Results: All mice that received mbTBI had a longer (p&amp;lt;0.05) righting time compared to those that did not. There was no main effect of parity in the righting time (p&amp;gt;0.1). PP mice who experienced mbTBI demonstrated a greater (p&amp;lt;0.05) CORT response to restraint (157.3 ± 21 pg/mL) when compared to NP mice (95.9 ± 7.2 pg/mL). CORT response to restraint did not differ (p&amp;gt;0.1) between NP and PP mice who did not experience mbTBI (96.1 ± 7.6 vs 109.2 ± 16 pg/mL). Conclusions: Our data indicates that mbTBI alters HPA axis reactivity in PP mice compared to NP mice, increasing the CORT response to restraint induced stress. Parity alone did not alter CORT response to restraint stress or baseline CORT levels. The results of our finding highlight the importance of parity as a factor in an individual’s lifespan. Presentation: Saturday, June 17, 2023

Modern content for personalized rehabilitation of patients with a consequences of traumatic brain injury

Objective: to substantiate the significance of quality of life indicators in the formation of modern content of personalized rehabilitation of patients with a consequences of traumatic brain injury. Material and methods. The study included 414 respondents of working age (93.6% men). 54% of the respondents had a traumatic brain injury within 1 to 5 years, in 62,0%, cases the traumatic brain injury was of severe degree. Longitudinal sociological study of the quality of life using the WHOQOL-100 questionnaire was carried out. The Dembo-Rubinstein test was used to diagnose the adequacy of self-assessment of the respondents with TBI. The dynamics of the respondents' neurological status and quality of life were assessed annually during 2020-2022. Results. In the annual study, 64.7% of respondents showed clinical deterioration in 96% of cases, which was manifested by increased severity of general cerebral symptoms, cognitive impairment, and asthenic syndrome. In 4.0% of cases new symptoms manifested (posttraumatic epilepsy). In the dynamic of respondents' quality of life, clinical deterioration in parameters "Physical sphere", "Psychological sphere", "Environment" and "General quality of life and health status" was revealed. Conclusion. In the absence of specific laboratory markers in clinical practice and not always sufficient informativeness of neuroimaging methods for the verification of the consequences of traumatic brain injury, the quality of life can be considered as an important criterion of prognosis, which determines the content of personalised rehabilitation of patients with the consequences of traumatic brain injury.