Effects Of Traumatic Brain Injury Research Articles

The experience of traumatic brain injury in a culturally and linguistically diverse sample in Australia

Purpose Individuals from culturally and linguistically diverse (CALD) backgrounds experience poorer outcomes following traumatic brain injury (TBI), including poorer quality of life. The reasons for these poorer outcomes are unclear. Therefore, this study aimed to qualitatively investigate the experience of injury, rehabilitation, and recovery amongst individuals from a CALD background following TBI. Materials and methods Fifteen semi-structured interviews were conducted, and qualitatively analysed using reflexive thematic analysis. Results It was demonstrated that: (a) the cognitive and behavioural consequences of TBI were accompanied by stigma and loss of independence; (b) participants held many beliefs related to their TBI, ranging from bad luck to acceptance. Participants’ personal values and beliefs provided strength and resilience, with many viewing the injury as a positive event in their lives; (c) participants were appreciative of the high standard of care they received in hospital and rehabilitation, although communication barriers were experienced; (d) many participants identified with Australian culture, and few believed their cultural background negatively impacted their experience of TBI; (e) external support, particularly from family, was considered central to recovery. Conclusion These findings offer insight into the challenges CALD individuals face and factors that may facilitate their recovery and improve functional outcomes.

Intraneuronal accumulation of amyloid-β peptides as the pathomechanism linking autism and its co-morbidities: epilepsy and self-injurious behavior - the hypothesis.

Autism spectrum disorder (ASD) is associated with enhanced processing of amyloid-β precursor protein (APP) by secretase-α, higher blood levels of sAPPα and intraneuronal accumulation of N-terminally truncated Aβ peptides in the brain cortex - mainly in the GABAergic neurons expressing parvalbumin - and subcortical structures. Brain Aβ accumulation has been also described in epilepsy-the frequent ASD co-morbidity. Furthermore, Aβ peptides have been shown to induce electroconvulsive episodes. Enhanced production and altered processing of APP, as well as accumulation of Aβ in the brain are also frequent consequences of traumatic brain injuries which result from self-injurious behaviors, another ASD co-morbidity. We discuss distinct consequences of accumulation of Aβ in the neurons and synapses depending on the Aβ species, their posttranslational modifications, concentration, level of aggregation and oligomerization, as well as brain structures, cell types and subcellular structures where it occurs. The biological effects of Aβ species which are discussed in the context of the pathomechanisms of ASD, epilepsy, and self-injurious behavior include modulation of transcription-both activation and repression; induction of oxidative stress; activation and alteration of membrane receptors' signaling; formation of calcium channels causing hyper-activation of neurons; reduction of GABAergic signaling - all of which lead to disruption of functions of synapses and neuronal networks. We conclude that ASD, epilepsy, and self-injurious behaviors all contribute to the enhanced production and accumulation of Aβ peptides which in turn cause and enhance dysfunctions of the neuronal networks that manifest as autism clinical symptoms, epilepsy, and self-injurious behaviors.

Analysis of cranioplasty procedures performed in Novosibirsk from 2016 to 2022

Background: Studies on reconstructive neurosurgical interventions are always relevant due to the persistence of cranial defects, mainly caused by traumatic brain injuries (TBI). To provide medical care to the patients with cranial defects more efficiently, it is necessary to assess a large number of surgical interventions in studies.Objective: To analyze data on reconstructive neurosurgical interventions performed at Novosibirsk hospitals.Methods: We performed a multicenter observational retrospective non-randomized study of the total cranioplasty surgical interventions from 2016 to 2022. The study involved five neurosurgical departments in Novosibirsk hospitals. In 450 of 673 cases the inclusion criteria were met.Results: The majority of patients (n = 361; 80.2%) underwent surgical interventions in federal health facilities. Urban residents prevailed (n = 260) among the patients who met the inclusion criteria. Craniectomies were mainly indicated for the consequences of TBI (n = 319; 70.9%). Time to cranioplasty ranged from 0.1 to 320 months (mean: 23.9 ± 39.2; median: 11.6 months). There were non-clinically significant differences in terms of primary and reconstructive operations between the defects caused by TBI and other conditions. In 51.1% of cases, we found two features describing the size and complexity of the skull defect. In 19.3% of cases, patients were diagnosed with a skull defect (affected anatomical areas were specified).Conclusions: Over seven years, 450 Novosibirsk residents underwent cranioplasty in five neurosurgical Novosibirsk hospitals (mean: 64.3 surgical interventions a year). Comparing the recent results with previous studies data in terms of performed craniectomies, we found that reconstructive interventions are lacking 99.7 cases per year. To reduce the time to cranioplasty, it is necessary to make a registry of patients with skull defects.

Depression Severity Is Different in Dysosmic Patients Who Have Experienced Traumatic Brain Injury Compared with Those Who Have Not.

Traumatic brain injury (TBI) in humans can result in olfactory, cognitive, and affective changes. Surprisingly, research on the consequences of TBI often did not control for olfactory function in the investigated groups. Consequently, the affective or cognitive differences might be misleading as related rather to different olfactory performance than to a TBI experience. Hence, our study aimed to investigate whether TBI occurrence would lead to altered affective and cognitive functioning in two groups of dysosmic patients, one with TBI experience and one without. In total, 51 patients with TBI experience and 50 controls with varied causes of olfactory loss were thoroughly examined in terms of olfactory, cognitive, and affective performance. Student t-tests demonstrated that the only significant difference between the groups appeared in the depression severity, with TBI patients being more depressed (t = 2.3, p = 0.011, Cohen's d = -0.47). Regression analyses further showed that TBI experience was significantly associated with depression severity (R2 = 0.05, F [1, 96] = 5.5, p = 0.021, beta = 1.4). In conclusion, the present study showed that TBI experience is linked to depression, which is more pronounced compared to individuals with olfactory loss without TBI.

A systematic review of heart rate variability (HRV) biofeedback treatment following traumatic brain injury (TBI)

ABSTRACT Objective Autonomic nervous system dysregulation is a common consequence of traumatic brain injury (TBI). Heart rate variability (HRV) is a cost-effective measure of autonomic nervous system functioning, with studies suggesting decreased HRV following moderate-to-severe TBI. HRV biofeedback treatment may improve post-TBI autonomic nervous system functioning and post-injury emotional and cognitive functioning. We provide a systematic evidence-based review of the state of the literature and effectiveness of HRV biofeedback following TBI. Method We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two coders coded each article and provided quality ratings. Seven papers met inclusion criteria. All studies included a measure of emotional functioning and 5 studies (63%) included neuropsychological outcomes. Results Participants completed 11 sessions of HRV biofeedback on average (range = 1 to 40). HRV biofeedback was associated with improved HRV following TBI. There was a positive relationship between increased HRV and TBI recovery following biofeedback, including improvements in cognitive and emotional functioning, and physical symptoms such as headaches, dizziness, and sleep problems. Conclusion The literature on HRV biofeedback for TBI is promising, but in its infancy; effectiveness is unclear due to poor-to-fair study quality, and potential publication bias (all studies reported positive results).

Using home monitoring technology to study the effects of traumatic brain injury on older multimorbid adults: protocol for a feasibility study

IntroductionThe prevalence of traumatic brain injury (TBI) among older adults is increasing exponentially. The sequelae can be severe in older adults and interact with age-related conditions such as multimorbidity. Despite...

Effects of traumatic brain injury on blood pressure regulation and cardio-renal function in rats

Traumatic Brain Injury (TBI) affects around 68 million people worldwide annually. While the neurologic effects of TBI have been extensively studied, potential effects on the autonomic nervous system have received less attention, despite clinical observations of autonomic dysfunction. We therefore sought to develop a rat model of repeated traumatic brain injury to examine the effects on cardiovascular and renal regulation, and we hypothesized that TBI would result in autonomic dysregulation of cardio-renal function. TBI was induced in male rats (250-300 gBW) under brief isoflurane anesthesia by dropping a 245g weight from a height of 1-1.5 meters onto the mid-sagittal area of the skull while the rat was suspended on a perforated tear-away platform. In the first series of experiments, blood pressure was measured continuously by telemetry over a two-week period, while rats were subjected to three successive injuries, each separated by 48 hours (repeated TBI, rTBI). Mean blood pressure was found to increase by about 7 mmHg following the third TBI (104.0 ± 1.1 to 111.0 ± 1.3 mmHg; p < 0.001, n=9). Though mild, the elevation in blood pressure was highly consistent, occurring in all of the injured rats. There were no correlate changes in heart rate observed in these rats. We then sought to examine the underlying causes of these blood pressure changes. Balance studies were performed using metabolic cages to examine salt and water intake and output before and during rTBI. Though intake of food and water were slightly affected by rTBI, no measurable effect of rTBI was observed on salt and water balance in these rats. We next measured cardiac function in anesthetized rats following rTBI and found no significant differences in any major contractile variables (LV systolic pressure, dP/tmax, dP/dtmin). In a final series of experiments, we evaluated renal blood flow during step-wise reductions in renal perfusion pressure using an aortic clamp and found that, while blood flow autoregulation was not impaired in rTBI rats, baseline renal blood flow was mildly reduced in injured rats compared to uninjured controls (3.44 ± 0.16 vs 3.94 ± 0.05 mL/min/gKW). In summary, we have generated a rat model of repeated traumatic brain injury that results in a consistent elevation of resting arterial blood pressure. Speculation that these observed changes may result from autonomic dysregulation remains to be investigated. University of Cincinnati College of Medicine Innovation Seed Grant This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evaluation of hemorrhagic shock and traumatic brain injury effects on hemodynamics and metabolomics

Traumatic brain injury (TBI) is often accompanied by hemorrhage. However, treatment of hemorrhagic shock (HS) after TBI is challenging because the treatment strategies for TBI and HS often conflict. Little is known about the complex pathophysiological differences between these two traumas when happening individually or combined. The aim of the present study was to evaluate effects of HS and TBI individually and combined on hemodynamics, baroreflex and brain metabolomics. Male Wistar rats were instrumented with catheters and subjected to TBI through a pneumatic controlled cortical impact. HS was induced by blood withdrawal to achieve a blood pressure (BP) between 35-40mmHg, and this hypotensive state was maintained for 90 min. Animals were separated into 4 groups (n=5): Sham (underwent surgery, but no TBI or HS was done), HS (animals were placed in the stereotaxic, but no TBI), TBI (TBI was performed and timeline was followed as described, but no HS was done), and TBI+HS. Rats were sacrificed 90 min after HS and tissues were harvested. BP, heart rate (HR), and indices of spontaneous baroreflex sensitivity were evaluated at baseline, 10 min after TBI, and at 10 and 90 min after HS. The brain was harvested and a metabolomic analysis for tricarboxylic acid (TCA) cycle, amino acids and lipids was performed in the impacted area. BP decreased in the TBI group compared to Sham and, as expected, it severely decreased in HS and TBI+HS groups, once they were kept at lower pressure levels for 90 min. Heart Rate (HR) was lower in the HS group compared to Sham and TBI groups. It was observed that HS decreases the BP alteration events’ number during a fixed 10 min period compared to Sham and TBI groups, however the association of TBI with HS normalized this parameter. This suggests that HS is decreasing BP variability in the HS group, while the association of HS with TBI did not show the same response. Baroreflex sensitivity was higher in both HS and HS+TBI compared to both Sham and TBI groups. TCA cycle and amino acids metabolites increased in all the groups with trauma compared to Sham, however the increase in the HS and TBI+HS was around 2.5X-fold, while for the TBI group it was around 1.5X-fold. Moreover, the lipids metabolites decreased for all the groups submitted to trauma, with the highest effects observed for the groups submitted to HS and TBI+HS. These results suggest that HS has a higher effect on metabolites abnormalities compared to TBI alone. Our results suggest that HS has a higher contribution for hemodynamics and metabolism abnormalities when compared to TBI alone. It is interesting that the association of TBI with HS does not seem to change parameters such HR and BP variability. However, further investigations are necessary to better understand the impact of the lack of alteration of these hemodynamics parameters, since this trauma combination is complex and the adequate treatment for these situations remains unclear. This study was supported by National Institutes of Health grants R01HL162120, R01HL159862 and the Department of Defense under grants W81XWH1810059. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18–86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

Loss of Consciousness and Righting Reflex Following Traumatic Brain Injury: Predictors of Post-Injury Symptom Development (A Narrative Review).

Identifying predictors for individuals vulnerable to the adverse effects of traumatic brain injury (TBI) remains an ongoing research pursuit. This is especially important for patients with mild TBI (mTBI), whose condition is often overlooked. TBI severity in humans is determined by several criteria, including the duration of loss of consciousness (LOC): LOC < 30 min for mTBI and LOC > 30 min for moderate-to-severe TBI. However, in experimental TBI models, there is no standard guideline for assessing the severity of TBI. One commonly used metric is the loss of righting reflex (LRR), a rodent analogue of LOC. However, LRR is highly variable across studies and rodents, making strict numeric cutoffs difficult to define. Instead, LRR may best be used as predictor of symptom development and severity. This review summarizes the current knowledge on the associations between LOC and outcomes after mTBI in humans and between LRR and outcomes after experimental TBI in rodents. In clinical literature, LOC following mTBI is associated with various adverse outcome measures, such as cognitive and memory deficits; psychiatric disorders; physical symptoms; and brain abnormalities associated with the aforementioned impairments. In preclinical studies, longer LRR following TBI is associated with greater motor and sensorimotor impairments; cognitive and memory impairments; peripheral and neuropathology; and physiologic abnormalities. Because of the similarities in associations, LRR in experimental TBI models may serve as a useful proxy for LOC to contribute to the ongoing development of evidence-based personalized treatment strategies for patients sustaining head trauma. Analysis of highly symptomatic rodents may shed light on the biological underpinnings of symptom development after rodent TBI, which may translate to therapeutic targets for mTBI in humans.

The Role of Inhaled Estradiol and Myrtenol, Alone and in Combination, in Modulating Behavioral and Functional Outcomes Following Traumatic Experimental Brain Injury: Hemodynamic, Molecular, Histological and Behavioral Study.

Traumatic brain injury (TBI) is an important and growing cause of disability worldwide, and its cognitive consequences may be particularly significant. This study assessed the neuroprotective impacts of estradiol (E2), myrtenol (Myr), and the combination of the two on the neurological outcome, hemodynamic parameters, learning and memory, brain-derived neurotrophic factor (BDNF) level, phosphoinositide 3-kinases (PI3K/AKT) signaling, and inflammatory and oxidative factors in the hippocampus after TBI. Eighty-four adult male Wistar rats were randomly divided into 12 groups with seven rats in each (six groups to measure intracranial pressure, cerebral perfusion pressure, brain water content, and veterinary coma scale, and six groups for behavioral and molecular studies): sham, TBI, TBI/vehicle, TBI/Myr, TBI/E2, and TBI/Myr + E2 (Myr 50mg/kg and E2 33.3μg/kg via inhalation for 30min after TBI induction). Brain injury was induced by using Marmarou's method. Briefly, a 300-g weight was dropped down from a 2-m height through a free-falling tube onto the head of the anesthetized animals. Veterinary coma scale, learning and memory, brain water content, intracranial pressure, and cerebral perfusion pressure were impaired following TBI, and inflammation and oxidative stress were raised in the hippocampus after TBI. The BDNF level and PI3K/AKT signaling were impaired due to TBI. Inhalation of Myr and E2 had protective effects against all negative consequences of TBI by decreasing brain edema and the hippocampal content of inflammatory and oxidant factors and also by improving BDNF and PI3K/AKT in the hippocampus. Based on these data, there were no differences between alone and combination administrations. Our results propose that Myr and E2 have neuroprotective effects on cognition impairments due to TBI.

Salt diet Induces Neuroinflammatory Response, Microbiome Dysregulation and Associated with Long-term Anxiety Following Repetitive Closed Head Injury. (S28.003)

<h3>Objective:</h3> Investigate the effects of salt diet on neuroinflammatory response, behavior, and microbiome dysregulation following repetitive closed head injury model. <h3>Background:</h3> Concussions continue to be a prominent public health concern, with an estimated 1.6–3.8 million incidences annually in the United States. Younger populations are experiencing the highest rates of concussion and nearly all athletic endeavors have some risk of concussive injury. Concerns surrounding the potential risks of long-term cognitive and medical outcomes made adolescent traumatic brain injury (TBI) a central focus of public attention. Coupled to these events, recent clinical studies have shown that lifestyle factors, including salt diet, constitute additional risk affecting TBI consequences and neuropathophysiological outcomes. However, the impact of salt diet on the pathophysiology of TBI and whether it exacerbates post-injury outcomes is still largely unknown. <h3>Design/Methods:</h3> We investigated if the exposure to a high salt diet (HSD) would alter hemodynamics, behavior, innate immune response and microbiome diversity after repetitive mild closed head injury in adolescent mice. Mice were injured with a three hit model (3HD) and then maintained on a HSD or standard diet (STD) for 12 weeks. <h3>Results:</h3> We found that HSD didn’t change systolic and diastolic blood pressure, and heart rate compared with STD group. HSD group was associated with worsening anxiety-like behavior at 12 weeks post diet administration. HSD induced microgliosis and proinflammatory microglial transcriptomic signature including upregulation in interferon gamma, Interferon beta, T cells proliferation pathways. Consistently, we found upregulation of proinflammatory Tumor necrotic factor (TNF) in brain compared to Sham-HSD and TBI-STD groups. HSD was the main driver of microbiome dysregulation in both TBI and Sham groups. We found that Eubacterium xylanophilum and Lachnospiraceae bacterium associated with an anxiety phenotype following injury at 12 weeks post diet administration. <h3>Conclusions:</h3> Salt diet associated with increasing risk of worsening anxiety and exacerbating chronic neuroinflammation post repetitive head injury. <b>Disclosure:</b> Dr. Izzy has received publishing royalties from a publication relating to health care. Taha Yahya has nothing to disclose. Dr. Cao has nothing to disclose. Mr. Albastaki has nothing to disclose. Dr. Waed has nothing to disclose. Ms. Chopra has nothing to disclose. Miss EKWUDO has nothing to disclose. Miss Kurdeikaite has nothing to disclose. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Brigham and Women’s Hospital. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Brigham and Women’s Hospital and Harvard Medical School. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Von Medical, Inc.. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Nova Southeastern University. Ms. Moraes Verissimo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Montachem Company. Dr. Cox has received personal compensation for serving as an employee of Anaerobe Systems. The institution of Dr. Cox has received research support from Infectious Disease Society. The institution of Dr. Cox has received research support from BrightFocus Foundation. Dr. Cox has received intellectual property interests from a discovery or technology relating to health care. Dr. Zafonte has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MYOMO. Dr. Zafonte has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kisbee. Dr. Zafonte has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. The institution of Dr. Zafonte has received research support from NIDILRR. The institution of Dr. Zafonte has received research support from NIH. The institution of Dr. Zafonte has received research support from FPHS study. Dr. Zafonte has received publishing royalties from a publication relating to health care. Michael J. Whalen has nothing to disclose.

The Long-Term Sequelae of Traumatic Brain Injury over 10 Years of Follow-Up-a Matched Cohort Study Based on Routine Data of a German Statutory Health Insurance Carrier.

The acute effects of traumatic brain injury (TBI) are well documented, but there is no systematic quantification of its long-term sequelae in German-language literature. The purpose of this article is to compare the frequency of conditions linked to prior TBI with their frequency in the non-brain-injured population. A matched cohort study was carried out on the basis of routine data from the BARMER statutory health insurance carrier. The exposure group consisted of patients treated over the period 2006-2009 for TBI at a variety of treatment intensities, including persons with multiple organ trauma. The control group consisted of BARMER insurees without prior TBI who were matched with the patients in the exposure group for age, sex, and pre-existing diseases. Late sequelae were sought in the routine data for a period of ten years after the injury. The outcome rates of the exposure and control groups were compared with Kaplan-Meier estimators and Poisson regression. 114 296 persons with TBI in the period 2006-2009 were included in the study. The mortality within ten years of TBI was 305 per 1000 individuals. The relative mortality in the exposure group was higher than that in control individuals of the same age and sex, with an incidence rate ratio (IRR) of 1.67 (95% confidence interval, [1.60; 1.74]). Immobility, dementia, epilepsy, endocrine disorders, functional disorders, depression, anxiety, cognitive deficits, headache, and sleep disorders were also more common in the exposure group. Persons with TBI requiring high-intensity treatment displayed the highest relative incidence rates of the conditions studied over 10 years of follow-up. Persons who had been admitted to the hospital because of TBI had higher relative incidence rates for epilepsy and dementia than those who had been cared for on an outpatient basis. Adverse sequelae of TBI can still be seen ten years after the exposure. These patients die earlier than persons without TBI and suffer earlier and more frequently from associated conditions.

RAGE Inhibitors in Neurodegenerative Diseases.

Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer's disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood-brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE-RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE-RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE-RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.

The Integrity of the Blood-Brain Barrier as a Critical Factor for Regulating Glutamate Levels in Traumatic Brain Injury.

A healthy blood-brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.

Sleep/Wake Disorders After Sports Concussion: Risks, Revelations, and Interventions.

Sleep-wake disturbances (SWDs) are among the most prevalent, persistent, and often disregarded sequelae of traumatic brain injury. Identification and treatment of SWDs in patients with traumatic brain injury is important and can complement other efforts to promote maximum functional recovery. SWDs can accentuate other consequences of traumatic brain injury, negatively affect mood, exacerbate pain, heighten irritability, and diminish cognitive abilities and the potential for recovery. The risk for sports injuries increases when athletes are sleep deprived. Sleep deprivation increases risk-taking behaviors, predisposing to injuries. SWDs are an independent risk factor for prolonged recovery after sports-related concussion. SWDs following sports-related concussion have been shown to impede recovery, rehabilitation, and return to preinjury activities.

Manual lesion segmentations for traumatic brain injury characterization.

Traumatic brain injury (TBI) often results in heterogenous lesions that can be visualized through various neuroimaging techniques, such as magnetic resonance imaging (MRI). However, injury burden varies greatly between patients and structural deformations often impact usability of available analytic algorithms. Therefore, it is difficult to segment lesions automatically and accurately in TBI cohorts. Mislabeled lesions will ultimately lead to inaccurate findings regarding imaging biomarkers. Therefore, manual segmentation is currently considered the gold standard as this produces more accurate masks than existing automated algorithms. These masks can provide important lesion phenotype data including location, volume, and intensity, among others. There has been a recent push to investigate the correlation between these characteristics and the onset of post traumatic epilepsy (PTE), a disabling consequence of TBI. One motivation of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is to identify reliable imaging biomarkers of PTE. Here, we report the protocol and importance of our manual segmentation process in patients with moderate-severe TBI enrolled in EpiBioS4Rx. Through these methods, we have generated a dataset of 127 validated lesion segmentation masks for TBI patients. These ground-truths can be used for robust PTE biomarker analyses, including optimization of multimodal MRI analysis via inclusion of lesioned tissue labels. Moreover, our protocol allows for analysis of the refinement process. Though tedious, the methods reported in this work are necessary to create reliable data for effective training of future machine-learning based lesion segmentation methods in TBI patients and subsequent PTE analyses.

Art therapy with military families: The animal strengths and family environment directive

Military families are resilient but are impacted by service member’s deployments, combat exposure, injuries, and other stressors such as frequent moves. These factors affect the entire family, and in turn family dynamics influence injured service members’ capacity to heal. Art therapy is a regulated mental health profession that incorporates the use of visual art to address psychological and rehabilitation treatment goals provided by qualified art therapists and has been used with military families in health settings for over 70 years. Through art therapy, military families can find new ways to communicate with one another in developmentally appropriate ways. This article describes the process of the Animal Strengths and Family Environment (ASFE), an art therapy directive designed to meet the needs of families of service members recovering from effects of traumatic brain injuries (TBI) and post-traumatic stress disorder (PTSD). Case vignettes are presented illustrating the use of the ASFE, describing how two military families identified character strengths through animal metaphors, and created visual artwork to discover and express these strengths, roles, and needs. The authors contend that this process is useful in mapping family dynamics to increase communication which ultimately fosters family resiliency. Continued research is needed to better understand possible outcomes of art therapy directives with military families.

How Traumatic Brain Injury History Relates to Brain Health MRI Markers and Dementia Risk: Findings from the 3C Dijon Cohort.

The long-term effects of traumatic brain injury (TBI) with loss of consciousness (LOC) on magnetic resonance imaging (MRI) markers of brain health and on dementia risk are still debated. To investigate the associations of history of TBI with LOC with incident dementia and neuroimaging markers of brain structure and small vessel disease lesions. The analytical sample consisted in 4,144 participants aged 65 and older who were dementia-free at baseline from the Three City -Dijon study. History of TBI with LOC was self-reported at baseline. Clinical Dementia was assessed every two to three years, up to 12 years of follow-up. A subsample of 1,675 participants <80 years old underwent a brain MRI at baseline. We investigated the associations between history of TBI with LOC and 1) incident all cause and Alzheimer's disease (AD) dementia using illness-death models, and 2) neuroimaging markers at baseline. At baseline, 8.3% of the participants reported a history of TBI with LOC. In fully-adjusted models, participants with a history of TBI with LOC had no statistically significant differences in dementia risk (HR = 0.90, 95% CI = 0.60-1.36) or AD risk (HR = 1.03, 95% CI = 0.69-1.52), compared to participants without TBI history. History of TBI with LOC was associated with lower white matter volume (β= -4.58, p = 0.048), but not with other brain volumes, white matter hyperintensities volume, nor covert brain infarct. This study did not find evidence of an association between history of TBI with LOC and dementia or AD dementia risks over 12-year follow-up, brain atrophy, or markers of small vessel disease.

Adult-Born Granule Cells Contribute to Dentate Gyrus Circuit Reorganization after Traumatic Brain Injury.

Post-traumatic epilepsy (PTE) is a serious consequence of traumatic brain injury (TBI). PTE develops following a latent postinjury period during which alterations in neuronal network excitability are thought to occur, leading to the development of recurrent and unprovoked seizures. In particular,