Traumatic Brain Injury Injury Research Articles

Psychedelics for Brain Injury: A Mini-Review.

Objective: Stroke and traumatic brain injury (TBI) are among the leading causes of disability. Even after engaging in rehabilitation, nearly half of patients with severe TBI requiring hospitalization are left with major disability. Despite decades of investigation, pharmacologic treatment of brain injury is still a field in its infancy. Recent clinical trials have begun into the use of psychedelic therapeutics for treatment of brain injury. This brief review aims to summarize the current state of the science's relevance to neurorehabilitation, and may act as a resource for those seeking to understand the precedence for these ongoing clinical trials.Methods: Narrative mini-review of studies published related to psychedelic therapeutics and brain injury.Results: Recent in vitro, in vivo, and case report studies suggest psychedelic pharmacotherapies may influence the future of brain injury treatment through modulation of neuroinflammation, hippocampal neurogenesis, neuroplasticity, and brain complexity.Conclusions: Historical data on the safety of some of these substances could serve in effect as phase 0 and phase I studies. Further phase II trials will illuminate how these drugs may treat brain injury, particularly TBI and reperfusion injury from stroke.

Prognostic Value of Hemorrhagic Brainstem Injury on Early Computed Tomography: A TRACK-TBI Study.

Traumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge in TBI study were studied. Patients with brainstem and cerebrum injury (BSI+) were matched by age, sex, and admission Glasgow Coma Scale (GCS) score to patients with cerebrum injuries only. All patients had an interpretable head computed tomography (CT) scan from the first 48 hours after injury and a 6-month Glasgow Outcome Scale Extended (GOSE) score. CT scans were reviewed for brainstem lesions and, when present, characterized by location, size, and type (traumatic axonal injury, contusion, or Duret hemorrhage). Clinical, demographic, and outcome data were then compared between the two groups. Mann-Whitney U-tests showed no significant difference in 6-month GOSE scores in patients with BSI+ (mean 2.7) compared with patients with similar but only cerebrum injuries (mean 3.9), although there is a trend (p=0.10). However, subclassification by brainstem lesion type, traumatic axonal injury (mean 4.0) versus Duret hemorrhage or contusion (mean 1.4), did identify a proportion of BSI+ with significantly less favorable outcome (p=0.002). The incorporation of brainstem lesion type (traumatic axonal injury vs. contusion/Duret), along with GCS into a multivariate logistic regression model of favorable outcome (GOSE score 4-8) did show a significant contribution to the prognostication of this brainstem injury subgroup (odds ratio 0.08, 95% confidence interval 0.00-0.67, p=0.01). These findings suggest two groups of patients with brainstem injuries may exist with divergent recovery potential after TBI. These data support the notion that newer CT imaging classification systems may augment traditional clinical measures, such as GCS in identifying those patients with TBI and brainstem injuries that stand a higher chance of favorable outcome.

Post-Concussion and Post-Traumatic Stress Symptoms after Pediatric Traumatic Brain Injury: Shared Vulnerability Factors?

Following pediatric traumatic brain injury (TBI), post-concussion symptoms (PCS) and post-traumatic stress symptoms (PTSS) occur commonly; however, it is unknown to what degree they overlap. The study examined PCS and PTSS persisting 7 weeks after injury in children and adolescents ages 8-15 years with TBI (n = 89) or extracranial injury (EI; n = 40) after vehicle collisions. TBI was divided into mild, complicated-mild/moderate, and severe groups. Parents retrospectively rated children's pre-injury symptoms and behavior problems, and children completed self-report measures after injury. PCS and PTSS total scores were significantly correlated in TBI and EI groups, respectively, for child (rs = 0.75; rs = 0.44), and adolescent (rs = 0.61; rs = 0.67) cohorts. Generalized linear models examined whether injury type and severity, age, sex, and pre-injury symptom ratings predicted PCS and PTSS total scores and factor scores. Specific PCS and PTSS factor scores were elevated in different TBI severity groups, with most frequent problems following mild or severe TBI. PCS did not differ by age; however, girls had more emotional symptoms than boys. Only PTSS were predicted by pre-injury externalizing behavior. Significant age by sex interactions indicated that adolescent girls had more total, avoidance, and hyperarousal PTSS symptoms than younger girls or all boys. PCS and PTSS significantly overlapped in both TBI and EI groups, highlighting shared persistent symptoms after injury. Shared vulnerability factors included female sex, milder TBI, and poorer pre-injury adjustment. Older age was a unique vulnerability factor for PTSS. Psychological health interventions after injury should be customized to address comorbid symptoms.

The Boston Assessment of Traumatic Brain Injury-Lifetime Semistructured Interview for Assessment of TBI and Subconcussive Injury Among Female Survivors of Intimate Partner Violence: Evidence of Research Utility and Validity.

To adapt the Boston Assessment of TBI-Lifetime (BAT-L) interview specifically for female survivors of intimate partner violence (IPV), validate the adapted BAT-L/IPV, and report the prevalence of head injury. The BAT-L is the first validated instrument to diagnose traumatic brain injuries (TBIs) throughout the life span for post-9/11 veterans. The BAT-L/IPV was adapted to target diagnostic issues belonging exclusively to IPV while maintaining its life span approach. Community-dwelling convenience sample of 51 female survivors of IPV with subthreshold (n = 10) or full diagnostic criteria (n = 41) of posttraumatic stress disorder. Standard TBI criteria were evaluated using a semistructured clinical interview. The BAT-L/IPV is compared with the Ohio State University TBI Identification Method (OSU-TBI-ID) scoring approach as the criterion standard. Correspondence between the BAT-L/IPV and the OSU-TBI-ID score was excellent (Cohen κ = 0.86; Kendall τ-b = 0.89). Sensitivity = 89.3% (95% CI, 81.2-97.4); specificity = 98.3% (95% CI, 95.0-100); positive predictive value = 98.0% (95% CI, 94.2-100); and negative predictive value = 90.6% (95% CI, 83.5-97.7). On the BAT-L/IPV, more than one-third (35.3%) of IPV survivors reported TBI secondary to an IPV-related assault, 76.5% reported IPV subconcussive head injury, 31.4% reported attempted strangulation, and 37.3% reported non-IPV TBI. The BAT-L/IPV performed well in diagnosing TBI in female IPV survivors as compared with the criterion standard. The prevalence of TBI was frequent; subconcussive head injury was pervasive. Greater awareness for head injury risk and increased diagnostic specificity of TBI in IPV survivors is needed.

Effect of Hyperbaric Oxygen Therapy on Polarization Phenotype of Rat Microglia After Traumatic Brain Injury.

Background: The neurological defect caused by secondary damage following traumatic brain injury (TBI) is considered critical for the management of TBI. Microglia (MG) are a resident brain macrophage that could differentiate into M1 type or M2 type in response to injury and repair. It is known that the MG transition from M1 phenotype to anti-inflammatory M2 phenotype might reduce secondary injury of TBI. So, a TBI animal model was established and we compared biomarkers of M1 and M2MG between the controls and experimental animals receiving hyperbaric oxygen therapy (HBOT). This study aimed to explore whether HBOT was an effective method to improve neural functional recovery via promoting the polarization of MG into M2 after TBI.Methods: The rats were randomly divided into four groups: SH (Sham-operated), SH + HBO (hyperbaric oxygen), TBI, and TBI + HBO. Each group included 42 rats, and each of these were divided into the following groups: 1, 6, 12, 24, 72 h, 7, and 14 days. The expression of M1 biomarker inducible nitric oxide synthase (iNOS), M2 biomarker arginase 1 (Arg1), associated cytokine tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1) was evaluated after the observation time.Results: TBI significantly increased the expression levels of M1 marker iNOS and M2 markers Arg1 at different time points. The increased expression of iNOS was suppressed, while the expression level of Arg1 was enhanced by HBOT. Moreover, HBOT suppressed the pro-inflammatory TNF-α secreted by M1, and promoting the anti-inflammatory TGF-1β.Conclusions: In the present study, HBOT showed the effects on shift of M1 toward M2 phenotype with increased expression of M2 biomarkers and decreased expression of M1 biomarkers in the early stage after TBI.

Oral Administration of Brain Protein Combined With Probiotics Induces Immune Tolerance Through the Tryptophan Pathway.

Excessive inflammation leads to secondary immune damage after traumatic brain injury (TBI). The intestinal mucosa is a key component of immune tolerance due to gut-brain axis regulation, but the curative effect is not optimal. Intestinal dysfunction impairs the establishment of immune tolerance in patients with TBI. Therefore, we orally administered brain protein (BP) combined with probiotics to induce immune tolerance and explored the mechanism by which the homeostasis of the microbiota contributes to the enhancement of curative effects by BPs. Herein, we demonstrated that patients with TBI and surgical brain injury (SBI) models of rats had obvious dysbiosis. Notably, the intestinal barrier, proinflammatory cytokines, and activation of microglia demonstrated that excessive inflammatory damage was better controlled in the combined group (oral administration of BP combined with probiotics) than in the BP group (oral administration of BP). Fundamentally, tandem mass tag (TMT)-based quantitative proteomics analysis revealed that BP and probiotics preferentially affect Try-related pathways. A series of experiments further confirmed that Indoleamine 2,3 dioxygenase (IDO)/Kynurenine (Kyn)/Aryl hydrocarbon receptor (AhR) expression was high in the BP group, while Tryptophan hydroxylase 1(TpH1)/5-hydroxytryptamine (5-HT) only changed in the combined group. This study suggests that probiotics can enhance the efficacy of oral BP-induced immune tolerance through the Try pathway.

Incidence and Clinical Impact of Myocardial Injury Following Traumatic Brain Injury: A Pilot TRACK-TBI Study.

Traumatic brain injury (TBI) is a major global health problem. Little research has addressed extracranial organ dysfunction following TBI, particularly myocardial injury. Using a sensitive marker of myocardial injury-high sensitivity troponin (hsTn)-we examined the incidence of early myocardial injury following TBI and explored its association with neurological outcomes following moderate-severe TBI. We conducted a pilot cohort study of 133 adult (age above 17 y) subjects enrolled in the TRACK-TBI 18-center prospective cohort study. Descriptive statistics were used to examine the incidence of myocardial injury (defined as hsTn >99th percentile for a standardized reference population) across TBI severities, and to explore the association of myocardial injury with a 6-month extended Glasgow Outcome Score among patients with moderate-severe TBI. The mean (SD) age of the participants was 44 (17) years, and 87 (65%) were male. Twenty-six patients (20%) developed myocardial injury following TBI; myocardial injury was present in 15% of mild TBI patients and 29% of moderate-severe TBI patients (P=0.13). Median (interquartile range) hsTn values were 3.8 ng/L (2.1, 9.0), 5.8 ng/L (4.5, 34.6), and 10.2 ng/L (3.0, 34.0) in mild, moderate, and severe TBI participants, respectively (P=0.04). Overall, 11% of participants with moderate-severe TBI and myocardial injury experienced a good outcome (6-mo extended Glasgow Outcome Score≥5) at 6 months, compared with 65% in the group that did not experience myocardial injury (P=0.01). Myocardial injury is common following TBI, with a likely dose-response relationship with TBI severity. Early myocardial injury was associated with poor 6-month clinical outcomes following moderate-severe TBI.

Trajectories of Children's Executive Function After Traumatic Brain Injury

Executive functions are critical for school and social success. Although these functions are adversely affected by pediatric traumatic brain injury (TBI), recovery patterns are not well established. To examine 3-year trajectories of selected children's executive functions after TBI. This prospective cohort study was conducted from January 22, 2013, to September 30, 2015, with 3-year follow-up at the level I pediatric trauma centers Primary Children's Hospital in Salt Lake City, Utah and Children's Memorial Hermann Hospital in Houston, Texas. Study participants included children aged 2 to 15 years with TBI or orthopedic injury (OI) who were treated at the participating hospitals. Children were consecutively recruited and stratified by injury severity and age group. A total of 625 children consented and completed a baseline survey; 559 (89%) children completed at least 1 follow-up and composed the analysis cohort. It was hypothesized that recovery would differ by injury severity, age at injury, and sex. Data analyses were performed from June to October 2019. Growth curve models examined the pattern of change in the Emotional Control, Inhibit, Working Memory, and Plan-Organize subscales of the Behavior Rating Inventory of Executive Function (BRIEF) or BRIEF-Preschool. For all BRIEF subscales, higher scores indicate worse symptoms, and a score of 65 or greater represents clinical impairment. A total of 559 children (mean [SD] age, 8.6 [4.4] years; 356 boys [64%], 328 non-Hispanic White children [59%]) were included in the study: 155 (28%) children had mild TBI, 162 (29%) had complicated mild or moderate TBI, 90 (16%) had severe TBI, and 152 (27%) had OI. Growth curve trajectories varied by BRIEF subscale and injury severity. Overall, children with TBI did not return to their preinjury baseline, with a stepwise worsening of each outcome at 36 months by TBI severity compared with OI. Among children with severe TBI, trajectories accelerated fastest, indicating increased problems, from injury to 12 months for the Emotional Control (9.0 points; 95% CI, 6.0-11.9 points), Inhibit (3.6 points; 95% CI, 1.6-5.6 points), and Working Memory (7.0 points; 95% CI, 4.1-9.9 points) subscales. Their trajectories plateaued, with a secondary acceleration before 36 months for the Emotional Control and Working Memory subscales. Children with mild TBI had worse 36-month scores on all subscales except Inhibit compared with OI. Recovery patterns were similar for boys and girls. In this longitudinal cohort study of children with TBI, trajectory analysis revealed that some children worsen after a recovery plateau, suggesting a need for longitudinal reassessment beyond 1 year postinjury.

Poorer sleep quality predicts melatonin response in patients with traumatic brain injury: findings from a randomized controlled trial.

A recent clinical trial demonstrated that melatonin treatment was effective in improving self-perceived sleep quality in patients with traumatic brain injury (TBI); however, it remains unclear which patients benefited from melatonin treatment. To that end, findings from the clinical trial were re-examined to identify possible predictors of treatment response. Hierarchical multiple regression was used to identify patient characteristics, TBI injury characteristics, and self-report measures assessing sleep, fatigue, mood, and anxiety symptomatology that may uniquely explain a change in self-reported sleep quality scores (follow-up minus baseline score) as assessed by the Pittsburgh Sleep Quality Index (PSQI). After controlling for patient demographic and TBI injury-related variables, baseline self-report measures of sleep, fatigue, mood, and anxiety explained an additional 32% of the variance in change in PSQI scores. However, only baseline PSQI score made a unique and statistically significant contribution (β = -0.56, P = .006). After controlling for patient and TBI characteristics, baseline PSQI scores further explained 27% of the variance in change in PSQI scores (R2 change = .27, F1, 27 change = 11.79, P = .002). The standardized β for baseline PSQI score revealed a statistically significant negative relationship with change in PSQI score (β = -0.54, P = .002), revealing that higher PSQI score at baseline was associated with better sleep outcomes. In a sample comprising predominantly severe TBI and comorbid insomnia, participants who report poorer sleep quality have the most to gain from melatonin treatment irrespective of time since injury, demographics, fatigue, daytimes sleepiness, mood, and anxiety symptomology. Registry: Australian New Zealand Clinical Trials Registry; Name: Efficacy of Melatonin for Sleep Disturbance Following Traumatic Brain Injury; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=343083&showOriginal=true&isReview=true; Identifier: ACTRN12611000734965. Grima NA, Rajaratnam SMW, Mansfield D, McKenzie D, Ponsford JL. Poorer sleep quality predicts melatonin response in patients with traumatic brain injury: findings from a randomized controlled trial. J Clin Sleep Med. 2021;17(8):1545-1551.

Children who sustained traumatic brain injury take longer to fall asleep compared to children who sustained orthopedic injuries: actigraphy findings

ABSTRACT Objective: Primary: to examine objective sleep outcomes in children who sustained moderate to severe traumatic brain injury (TBI). Secondary: to examine the relation of objective sleep with subjective sleep, fatigue, and injury variables. Setting: A single tertiary brain injury unit. Participants: Children (5–15 years) with moderate to severe TBI (n = 23) or orthopedic injury (OI; n = 13). Design: Cohort study. Measures: Primary: objective sleep measure (actigraphy watch). Secondary: subjective sleep measure (questionnaire), fatigue questionnaire, and injury variables. Results: On actigraphy, children with TBI had longer sleep onset latency compared to children with OI. On the sleep questionnaire, children with TBI obtained higher scores for total sleep disturbance, initiating and maintaining sleep, and excessive somnolence. On the fatigue questionnaire, greater difficulties were found for total, sleep/rest, and cognitive fatigue for the TBI group. In the TBI group, actigraphy data did not correlate with sleep questionnaire, fatigue, or injury variables. Conclusion: Our study showed evidence of objective and subjective sleep disturbance in children with moderate to severe TBI, but these two types of sleep measures were not related. It is possible that distinct mechanisms underpin objective and subjective sleep disturbance, which may require different interventions.

Long noncoding RNA NKILA transferred by astrocyte-derived extracellular vesicles protects against neuronal injury by upregulating NLRX1 through binding to mir-195 in traumatic brain injury.

The study aims to investigate the effects of long noncoding RNA (lncRNA) transmitted nuclear factor-κB interacting lncRNA (NKILA)-containing astrocyte-derived small extracellular vesicles (EVs) on traumatic brain injury (TBI). TBI was modeled in vitro by exposing human neurons to mechanical injury and in vivo by controlled cortical impact in a mouse model. The gain- and loss-function approaches were conducted in injured neurons to explore the role of NKILA, microRNA-195 (miR-195) and nucleotide-binding leucine-rich repeat containing family member X1 (NLRX1) in neuronal injury. EVs extracted from NKILA-overexpressing astrocytes were used to treat injured neurons. It was revealed that NKILA was downregulated in injured neurons. Astrocyte co-culture participated in the upregulation of NKILA in injured neurons. Additionally, NKILA could competitively bind to miR-195 that directly targeted NLRX1. Next, the upregulation of NLRX1 or NKILA relived neuronal injury by promoting neuronal proliferation but inhibiting apoptosis. Astrocyte-derived EVs transferred NKILA into neurons, which led to the downregulation of miR-195, upregulation of NLRX1, increased cell proliferation, and decreased cell apoptosis. The in vivo experiments validated that NKILA-containing EVs promoted brain recovery following TBI. Collectively, astrocyte-derived EVs carrying NKILA was found to alleviate neuronal injury in TBI by competitively binding to miR-195 and upregulating NLRX1.

Syllabic Diadochokinesis in Adults With and Without Traumatic Brain Injury: Severity, Stability, and Speech Considerations.

Purpose Syllabic diadochokinesis (DDK) is a standard assessment task for motor speech disorders. This study aimed to compare rate and regularity of DDK according to the presence or absence of traumatic brain injury (TBI) and severity of TBI, examine the stability of DDK over time, and explore associations between DDK and extemporaneous speech. Method Military service members and veterans were categorized into three groups: no history of TBI (control), uncomplicated mild TBI (mTBI), and moderate through severe (including penetrating) TBI (msTBI). Participants produced rapid alternating-motion and sequential-motion syllable repetitions during one or two sessions. A semi-automated protocol determined syllabic rate and regularity. Perceptual ratings of selected participants' connected speech samples were compared to DDK results. Results Two hundred sixty-three service members and veterans provided data from one session and 69 from two sessions separated by 1.9 years (SD = 1.0). DDKs were significantly slower overall for mTBI and msTBI groups compared to controls. Regularity of productions did not differ significantly across groups. A significant Group × Task interaction revealed that the msTBI group produced sequential-motion syllable repetitions but not alternating-motion repetitions with greater regularity, whereas the opposite occurred for control and mTBI groups. DDK results did not differ significantly between sessions. Perceptual speech analysis for 30 participants, including 20 with atypical or questionable DDK performance, revealed two participants with mildly abnormal speech. Conclusions Overall, DDK productions are slower than normal in adults with moderate, severe, and penetrating TBI and are stable over time. Regularity of productions did not differentiate groups, although this result differed according to task. There were surprisingly few people identified with disordered speech, making comparisons to DDK data tenuous, and indicating that dysarthria is a rare complication in a population of adults with mostly uncomplicated mTBI who are not selected from referrals to a speech-language pathology clinic.

Brain interstitial glycerol correlates with evolving brain injury in paediatric traumatic brain injury

A better understanding of the complex pathophysiology of traumatic brain injury (TBI) is needed to improve our current therapies. Cerebral microdialysis (CMD) is an advanced method to monitor the brain, but little is known about its parameters in children. Brain glycerol, one of the CMD variables, is an essential component of the phospholipid bilayer cell membrane and is considered a useful marker of tissue hypoxia in adults. This study examined the time course of glycerol and its associations in paediatric TBI. In this retrospective cohort study, we collected data on children (< 13years) with severe TBI who underwent CMD monitoring. The relationship of glycerol was examined with respect to physiological, radiological variables, and clinical outcome. Twenty-eight children underwent CMD monitoring and had evaluable data. Lesion progression on head computed tomography (CT) demonstrated a strong relationship with glycerol (median glycerol, maximum and initial-to-maximum) when lesion size increased by > 30% (p=0.01, p=0.04 and p=0.004). Absolute glycerol values had a weak but statistically significant association with intracranial pressure and brain oxygenation. We did not find an association with clinical outcome. This is the first study to provide data on brain interstitial glycerol in children. CMD glycerol, particularly an increase from baseline, is associated with other markers of injury and with a significant increase in lesion size on repeat head CT. As such, it may represent a useful monitorable marker for evolving injury in paediatric TBI.

The clinical utility of the Children’s Communication Checklist-2 in children with early childhood traumatic brain injury

Objective Pediatric traumatic brain injury (TBI) is associated with long-term cognitive and behavioral deficits. Social communication impairments are common and impact functional outcomes, such as social engagement and academic performance. There are many barriers to identifying social communication deficits following TBI, including the absence of a standardized parent-reported communication measure for use in this population. The Children’s Communication Checklist—Second Edition (CCC-2) has demonstrated utility in identifying communication deficits in diagnoses other than TBI. This study investigated the clinical utility of the CCC-2’s social communication scales in children with TBI. Method: 203 children who sustained TBI or orthopedic injuries between the ages of 36 and 83 months were recruited as part of a larger, longitudinal study. We analyzed social communication subscale scores from the CCC-2 an average of 3.5 years postinjury. We used binary logistic regression analyses to examine the measure’s accuracy in classifying children with and without social communication deficits on other measures of pragmatic language and social competence. Correlation analyses and linear mixed models were used to examine the construct validity of the CCC-2. Results: The CCC-2 was able to accurately classify those with and without pragmatic language impairments on the Comprehensive Assessment of Spoken Language 92% of the time (sensitivity = 55%) and 96% of the time on the Home and Community Social Behavior scale (sensitivity = 72%). The CCC-2 demonstrated strong correlations with and predictive validity for measures of social communication and competence. Conclusions: The findings offer support for the clinical utility of the CCC-2 in the pediatric TBI population.

Traumatic brain injury with concomitant injury to the spleen: characteristics and mortality of a high-risk trauma cohort from the TraumaRegister DGU®

PurposeBased on the hypothesis that systemic inflammation contributes to secondary injury after initial traumatic brain injury (TBI), this study aims to describe the effect of splenectomy on mortality in trauma patients with TBI and splenic injury.MethodsA retrospective cohort analysis of patients prospectively registered into the TraumaRegister DGU® (TR-DGU) with TBI (AISHead ≥ 3) combined with injury to the spleen (AISSpleen ≥ 1) was conducted. Multivariable logistic regression modeling was performed to adjust for confounding factors and to assess the independent effect of splenectomy on in-hospital mortality.ResultsThe cohort consisted of 1114 patients out of which 328 (29.4%) had undergone early splenectomy. Patients with splenectomy demonstrated a higher Injury Severity Score (median: 34 vs. 44, p < 0.001) and lower Glasgow Coma Scale (median: 9 vs. 7, p = 0.014) upon admission. Splenectomized patients were more frequently hypotensive upon admission (19.8% vs. 38.0%, p < 0.001) and in need for blood transfusion (30.3% vs. 61.0%, p < 0.001). The mortality was 20.7% in the splenectomy group and 10.3% in the remaining cohort. After adjustment for confounding factors, early splenectomy was not found to exert a significant effect on in-hospital mortality (OR 1.29 (0.67–2.50), p = 0.45).ConclusionTrauma patients with TBI and spleen injury undergoing splenectomy demonstrate a more severe injury pattern, more compromised hemodynamic status and higher in-hospital mortality than patients without splenectomy. Adjustment for confounding factors reveals that the splenectomy procedure itself is not independently associated with survival.

Impact of pediatric traumatic brain injury on hippocampal neurogenesis.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity in the pediatric population. With advances in medical care, the mortality rate of pediatric TBI has declined. However, more children and adolescents are living with TBI-related cognitive and emotional impairments, which negatively affects the quality of their life. Adult hippocampal neurogenesis plays an important role in cognition and mood regulation. Alterations in adult hippocampal neurogenesis are associated with a variety of neurological and neurodegenerative diseases, including TBI. Promoting endogenous hippocampal neurogenesis after TBI merits significant attention. However, TBI affects the function of neural stem/progenitor cells in the dentate gyrus of hippocampus, which results in aberrant migration and impaired dendrite development of adult-born neurons. Therefore, a better understanding of adult hippocampal neurogenesis after TBI can facilitate a more successful neuro-restoration of damage in immature brains. Secondary injuries, such as neuroinflammation and oxidative stress, exert a significant impact on hippocampal neurogenesis. Currently, a variety of therapeutic approaches have been proposed for ameliorating secondary TBI injuries. In this review, we discuss the uniqueness of pediatric TBI, adult hippocampal neurogenesis after pediatric TBI, and current efforts that promote neuroprotection to the developing brains, which can be leveraged to facilitate neuroregeneration.

US Department of Defense Warfighter Brain Health Initiative: Maximizing performance on and off the battlefield.

The US Department of Defense (DoD) recognizes the importance of warfighter brain health with the establishment of the Warfighter Brain Health Initiative and Strategy. For a warfighter, also known as a service member, to perform at their highest level, cognitive and physical capabilities must be optimized. This initiative addresses brain health, brain exposures, to include blast overpressure exposures from weapons and munitions, traumatic brain injury (TBI), and long-term or late effects of TBI. The DoD's pursuit of maximal strength hinges on the speed of decisions (neurocognitive) and detection of brain injury when it occurs. The strategy creates a framework for deliberate, prioritized, and rapid development of end-to-end solutions for warfighter brain health. Through this strategy, DoD is addressing the needs of our service members, their families, line leaders/commanders, and their communities at large. The implications of this initiative and strategy are noteworthy for practitioners because the DoD Warfighter Brain Health construct lends itself to nurse practitioner engagement in clinical practice, patient education, policy development, and emerging research.

Current Management of Traumatic Brain Injury (TBI) May Lead to Subsequent Risk

Background: Traumatic brain injuries (TBI) present military health providers with expanded clinical responsibilities. Such injuries can lead to lifelong consequences and have a remarkable impact on society and the economy. Between 2000 and 2016, more than 350,000 US active-duty military service members have sustained a TBI. A population-based historical cohort study revealed that medical care costs for persons with TBI were an average of $4906 higher than costs for matched controls without TBI. Method: We conducted a peer-reviewed literature review. The hypothesis that arose indicates that the polytraumatic nature of TBI injuries and the complexity of diagnosing and managing care. A secondary hypothesis was veterans with mild and greater TBI were not being surveilled for latent sequelae. Results: During the past decades, following US military deployments, long combat operations engagements and numerous deployments increase TBI injuries. More than 80% of TBIs in US service members are clinically classified as mild TBI (mTBI). Unlike severe TBIs, the management of individuals with mTBI is still symptom-based, and guidelines continue to highlight nonpharmacologic interventions, and surveillance relies on patients' self-reported symptoms. This may lead to a missed diagnosis, management, or treatment procedure and a public health crisis for mTBI. Conclusion: To minimize the adverse effects of the injury, the recognition of veterans who bear mTBI, and the timely application of treatment and surveillance plans are essential. If service members have an untreated concussion and return to duty, they will be more vulnerable to subsequent injury, and their performance capability in critical situations can be diminished. Furthermore, they may be at risk for secondary brain injury that arises hours or days after the primary injury due to the release of pro-inflammatory mediators and the death of neural cells, even though they appear to have recovered, which contribute to further damage.

Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

Treatment of Swine Closed Head Injury with Perfluorocarbon NVX-428.

Pre-hospital treatment of traumatic brain injury (TBI) with co-existing polytrauma is complicated by requirements for intravenous fluid volume vs. hypotensive resuscitation. A low volume, small particle-size-oxygen-carrier perfluorocarbon emulsion NVX-428 (dodecafluoropentane emulsion; 2% w/v) could improve brain tissue with minimal additional fluid volume. This study examined whether the oxygen-carrier NVX-428 shows safety and efficacy for pre-hospital treatment of TBI. Anesthetized swine underwent fluid percussion injury TBI and received 1 mL/kg IV NVX-428 (TBI-NVX) at 15 min (T15) or normal saline (no-treatment) (TBI-NON). Similarly, uninjured swine received NVX-428 (SHAM-NVX) or normal saline (SHAM-NON). Animals were monitored and measurements were taken for physiological and neurological parameters before euthanasia at the six-hour mark (T360). Histopathological analysis was performed on paraffin embedded tissues. Physiological, biochemical and blood gas parameters were not different, with the exception of a significant but transient increase in mean pulmonary artery pressure observed in the TBI-experimental group immediately after drug administration. There were no initial differences in brain oxygenation at baseline, but over time oxygen decreased ~50% in both TBI groups. Histological brain injury scores were similar between TBI-NVX and TBI-NON, although a number of subcategories (spongiosis-ischemic/dead neurons-hemorrhage-edema) in TBI-NVX had a tendency for lower scores. The cerebellum showed significantly lower spongiosis and ischemic/dead neuron injury scores and a lower number of Fluoro-Jade-B-positive cerebellar-Purkinje-cells after NVX-428 treatment compared to controls. NVX-428 may assist in mitigating secondary cellular brain damage.