Troxerutin cerebroprotein hydrolysate injection ameliorates neurovascular injury induced by traumatic brain injury – via endothelial nitric oxide synthase pathway regulation

Abstract

Background: Neurovascular dysfunction caused by traumatic brain injury (TBI) is characterized by cerebralvascular damage, blood–brain barrier (BBB) breakdown, brain edema, etc. This study was designed to assess the protective role of 5 days troxerutin cerebroprotein hydrolysate (TCH) injection treatment against TBI, as well as the potential mechanism.

Methods: The weight-drop model of TBI in male Sprague-Dawley rats was chosen to induce TBI model, rats either with TCH or a vehicle via intraperitoneal injection were examined 3 days after TBI.

Results: TCH resulted in alleviation of neurological deficits, reduction of infarct volume, improvement of regional cerebral blood flow (rCBF), amelioration of neuronal death, astrocyte proliferation, endothelial cell loss, and BBB dysintegrity. These effects of TCH treatment against TBI were through endothelial nitric oxide synthase (eNOS) coupling/decoupling status adjustment, which not only increased nitric oxide (NO) level, but also decreased peroxynitrate level expression.

Conclusions: All the results indicated that TCH injection has multifaceted protective effects of neurovascular unit (NVU) against TBI via eNOS pathway regulation.     

Preliminary findings of altered functional connectivity of the default mode network linked to functional outcomes one year after pediatric traumatic brain injury

ABSTRACT

Purpose and Method: This study examined functional connectivity of the default mode network (DMN) and examined brain–behavior relationships in a pilot cohort of children with chronic mild to moderate traumatic brain injury (TBI). Results: Compared to uninjured peers, children with TBI demonstrated less anti-correlated functional connectivity between DMN and right Brodmann Area 40 (BA 40). In children with TBI, more anomalous less anti-correlated) connectivity between DMN and right BA 40 was linked to poorer performance on response inhibition tasks. Conclusion: Collectively, these preliminary findings suggest that functional connectivity between DMN and BA 40 may relate to longterm functional outcomes in chronic pediatric TBI.     

Hippocampal neuronal degeneration in the traumatic brain injury mouse: non-trivial effect of scalp incision

Objectives: In experimental models of traumatic brain injury (TBI), posttraumatic hippocampal neuronal degeneration in the cornu ammonis 1 (CA1), and/or the cornu ammonis 3 (CA3) regions are regarded as the most notable phenotypic appearances relating to the pathophysiology of human post-concussion syndrome. However, these morphological changes are often also seen in subjects without TBI, namely ‘sham’ groups. The frequencies and reasons of appearance of hippocampal neuronal degeneration in mice with TBI and/or sham are not clear.

Methods: We compared the frequencies of hippocampal neuronal degeneration among three groups: TBI (mice with external force impact performed by Marmarou’s weight drop model after scalp incision), sham (mice with scalp incision alone), and control (mice with neither external force impact nor scalp incision), using hematoxylin and eosin stain in day 6 (n = 5 in each group.) Isoflurane was used for anesthesia in all mice.

Results: The frequencies were 80, 100, and 20% in CA1, and 20, 40, and 60% in CA3, for TBI, sham, and control, respectively. In CA1, a significant difference of the frequency was observed between sham and control (p = 0.048), but not, between TBI and sham (p = 1.000) in Fisher’s exact test. In CA3, no significant difference in the frequency was observed between the three groups.

Conclusion: Scalp incision, rather than external impact force, might affect the CA1 hippocampal neuronal degeneration in mice with TBI. In addition, factor(s) other than external impact force or scalp incision may also cause hippocampal neuronal degeneration in both CA1 and CA3. Careful interpretation is needed concerning hippocampal neuronal degeneration induced by a weight drop device observed in mice with TBI.     

Traumatic brain injury history is associated with earlier age of onset of Alzheimer disease

Objective: This study examined whether a history of traumatic brain injury (TBI) is associated with earlier onset of Alzheimer disease (AD), independent of apolipoprotein ε4 status (Apoe4) and gender.Method: Participants with a clinical diagnosis of AD (n = 7625) were obtained from the National Alzheimer’s Coordinating Center Uniform Data Set, and categorized based on self-reported lifetime TBI with loss of consciousness (LOC) (TBI+ vs. TBI?) and presence of Apoe4. ANCOVAs, controlling for gender, race, and education were used to examine the association between history of TBI, presence of Apoe4, and an interaction of both risk factors on estimated age of AD onset.Results: Estimated AD onset differed by TBI history and Apoe4 independently (p’s < .001). The TBI+ group had a mean age of onset 2.5 years earlier than the TBI? group. Likewise, Apoe4 carriers had a mean age of onset 2.3 years earlier than non-carriers. While the interaction was non-significant (p = .34), participants having both a history of TBI and Apoe4 had the earliest mean age of onset compared to those with a TBI history or Apoe4 alone (M_Difference = 2.8 and 2.7 years, respectively). These results remained unchanged when stratified by gender.Conclusions: History of self-reported TBI can be associated with an earlier onset of AD-related cognitive decline, regardless of Apoe4 status and gender. TBI may be related to an underlying neurodegenerative process in AD, but the implications of age at time of injury, severity, and repetitive injuries remain unclear.     

Associations between traumatic brain injury from intimate partner violence and future psychosocial health risks in women

ObjectiveThe effects of traumatic brain injury (TBI) incurred during military service are widely studied; however, less is known about TBI resulting from intimate partner violence (“IPV-related TBI”). Women Veterans are at high risk for IPV, yet no research has examined future psychosocial health risks associated with IPV-related TBI history in this population.MethodsWe examined psychiatric and physical health outcomes, as well as IPV, in a sample of women Veterans who, at Time 1, reported IPV-related TBI with (n = 13) or without (n = 20) persistent symptoms; that is, symptoms such as memory problems, balance problems or dizziness, sensitivity to bright light, irritability, headaches, and sleep problems that began or got worse immediately following the IPV-related TBI and occurred within the past week. These women completed web-based surveys 18 months later (Time 2), which included validated measures of psychiatric and physical health symptoms as well as past-year IPV. We conducted linear regressions to model whether T1 IPV-related TBI with persistent symptoms predicted worse health outcomes at T2, in comparison to T1 IPV-related without persistent symptoms.ResultsControlling for significant covariates (i.e., military sexual trauma; MST), IPV-related TBI with persistent symptoms at Time 1 was associated with significantly worse outcomes at Time 2 across all health outcome domains (sr² range: 0.12–0.37). After controlling for MST and probable posttraumatic stress disorder (PTSD) at Time 1, IPV-related TBI with persistent symptoms at Time 1 remained significantly associated with worse Time 2 symptoms of insomnia, depression, and physical health (sr² range: 0.12–0.25).ConclusionWomen who experience IPV-related TBI with persistent symptoms are at higher risk for worse psychosocial health outcomes 18 months later. Findings necessitate screening IPV survivors for TBI with persistent symptoms and tailoring TBI and psychosocial interventions to reduce risk for ongoing health sequelae.     

Post-traumatic hypopituitarism and fatigue

ABSTRACT

Post-traumatic hypopituitarism (PTH) associated with chronic cognitive, psychiatric, and/or behavioural sequelae is common following moderate to severe traumatic brain injury (TBI). More specifically, due to a cascade of hormonal deficiencies secondary to PTH, individuals with TBI may experience debilitating fatigue that can negatively impact functional recovery, as it can limit participation in brain injury rehabilitation services and lead to an increase in maladaptive lifestyle practices. While the mechanisms underlying fatigue and TBI are not entirely understood, the current review will address the specific anatomy and physiology of the pituitary gland, as well as the association between pituitary dysfunction and fatigue in individuals with TBI.     

The relationship between SDF-1α/CXCR4 and neural stem cells appearing in damaged area after traumatic brain injury in rats

Abstract

Objective: The actual relationship between neural stem cells and SDF-1α/CXCR4 after brain injury has not yet been elucidated, although recent studies have speculated that stromal cell-derived factor-1α (SDF-1α) and its receptor, CXCR4, could contribute to neural stem cells migration after brain injury. In the present study, the temporal relationship between neural stem cells (NSCs) and SDF-1α/CXCR4 around a damaged area was investigated using a rat traumatic brain injury (TBI) model.

Methods: We used molecular biology techniques and immunohistochemistry to investigate the relationship between SDF-1α/CXCR4 expression and NSCs existence around a damaged area after TBI in the rat brain.

Results: SDF-1α mRNA expression and SDF-1α protein synthesis did not increase after TBI. However, SDF-1α leaked from the injured area and diffused into the cortex 1–3 days after TBI. Subsequently, the levels of CXCR4 mRNA expression and CXCR4 protein synthesis increased significantly. Many small cells with a nestin-positive cytoplasm and fibers also showed immunopositivity for both CXCR4 and SOX-2, but not for GFAP, 3–7 days after TBI. Moreover, a proportion of the CXCR4-positive cells and fibers also showed immunostaining for neurofilaments.

Discussion: These results suggest that the leaked SDF-1α attracted CXCR4-positive NSCs as well as elongated nerve fibers. It is considered that the SDF-1α/CXCR4 system in the brain contributes to neural stem cells appearance and maturation after TBI. Therefore, exploitation of the SDF-1α/CXCR4 system around a damaged area may improve the brain dysfunction after TBI.     

Validation and clinical utility of the executive function performance test in persons with traumatic brain injury

ABSTRACT

This study examined the relationships between the Executive Function Performance Test (EFPT), the NIH Toolbox Cognitive Function tests, and neuropsychological executive function measures in 182 persons with traumatic brain injury (TBI) and 46 controls to evaluate construct, discriminant, and predictive validity. Construct validity: There were moderate correlations between the EFPT and the NIH Toolbox Crystallized (r?=??.479), Fluid Tests (r?=??.420), and Total Composite Scores (r?=??.496). Discriminant validity: Significant differences were found in the EFPT total and sequence scores across control, complicated mild/moderate, and severe TBI groups. We found differences in the organisation score between control and severe, and between mild and severe TBI groups. Both TBI groups had significantly lower scores in safety and judgement than controls. Compared to the controls, the severe TBI group demonstrated significantly lower performance on all instrumental activities of daily living (IADL) tasks. Compared to the mild TBI group, the controls performed better on the medication task, the severe TBI group performed worse in the cooking and telephone tasks. Predictive validity: The EFPT predicted the self-perception of independence measured by the TBI-QOL (beta = ?0.49, p?<?.001) for the severe TBI group. Overall, these data support the validity of the EFPT for use in individuals with TBI.     

Large animal models of traumatic brain injury

Purpose/Aim: Animal models of traumatic brain injury (TBI) provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents. However, compared with rodents, large animals (e.g. swine, rabbit, sheep, ferret, etc.) show great advantages in modeling TBI due to the similarity of their brains to human brain. The aim of our review was to summarize the development and progress of common large animal TBI models in past 30 years.

Materials and Methods: Mixed published articles and books associated with large animal models of TBI were researched and summarized.

Results: We majorly sumed up current common large animal models of TBI, including discussion on the available research methodologies in previous studies, several potential therapies in large animal trials of TBI as well as advantages and disadvantages of these models.

Conclusions: Large animal models of TBI play crucial role in determining the underlying mechanisms and screening putative therapeutic targets of TBI.     

Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment

Objective: Medical history information regarding prior traumatic brain injury (TBI) usually relies on self-report, although little is known about the reliability of this information with regard to injuries sustained years or decades earlier. Even less is known about the reliability of self-reported medical history information in older individuals with cognitive impairment. To this end, we assessed the test-retest reliability of self-reported TBI history in a large, national sample. Methods: Participants (n = 4309) were older adults with intact cognition, mild cognitive impairment (MCI) and Alzheimer’s disease (AD) from the National Alzheimer’s Coordinating Center. Subjects provided TBI history information at baseline and one annual follow-up visit. Consistency of self-reported history of TBI with <5 minutes loss of consciousness (mLOC) and TBI with ≥5 mLOC reported at time 1 and 2 was analyzed across diagnostic groups. Results: Overall, subjects provided reports of TBI history at follow-up that were highly consistent with baseline reports (97.8–99.6% agreement), and Cohen’s kappa coefficients were all larger than .80 and statistically significant, maximum p < .001. Furthermore, level of cognitive impairment was not a significant predictor of consistency in reporting. Conclusions: These data are some of the first to suggest that self-report may be a consistent method of obtaining remote TBI history in the absence of medical records for older individuals, regardless of cognitive impairment.     

Hourly neurologic assessments for traumatic brain injury in the ICU

Abstract

Objectives: Hourly neurologic assessments for traumatic brain injury (TBI) in the critical care setting are common practice but prolonged use may actually be harming patients through sleep deprivation. We reviewed practice patterns at our institution in order to gain insight into the role of frequent neurological assessments.

Methods: A 6-month retrospective review was performed for patients who were admitted to an intensive care unit (ICU) with the diagnosis of TBI. Electronic medical records were reviewed based on billing codes. Variables collected included but were not limited to patient demographics, frequency of nursing neurologic evaluations, Glasgow coma scale (GCS), length of stay (LOS), and disposition.

Results: A total of 124 patients were identified, 71% male with the average age of 52 years (range 19–96). Traumatic brain injury was classified as severe in 44, moderate in 18, and mild in 62 patients. A total of 89 (71·8%) patients underwent hourly nursing assessments for an average of 2·82 days. The median LOS for all patients was 7 days (range 0–109). There were 18 patients who remained on hourly neurological assessments for greater than 4 days and had a greater LOS (23 days vs 9 days, P = 0·001). Only two patients required surgery after 48 hours, both for chronic subdural hematomas.

Discussion: Hourly neurologic checks are necessary in the acute period for patients with potentially expansible intracranial hemorrhages or malignant cerebral edema, but prolonged use may be harmful. Patients with a low probability of requiring neurosurgical intervention may benefit from reducing the total duration of hourly assessments.     

Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain injury model via activation of PI3K/Akt signaling pathway

Objective: Neuronal autophagy and apoptosis play an irreplaceable role in brain injury pathogenesis and may represent a hopeful target for treatment. Previous studies have demonstrated that administration of quercetin-attenuated brain damage in a variety of brain injury models including traumatic brain injury (TBI). However, whether PI3K/Akt signaling pathway mediates the neuroprotection of quercetin following TBI is not well clarified. We sought to propose a hypothesis that quercetin could attenuate neuronal autophagy and apoptosis via enhancing PI3K/Akt signaling.

Methods: All rats were randomly arranged into four groups as follows: sham group (n = 25), TBI group (n = 25), TBI + quercetin group (n = 25), TBI + quercetin + LY294002 group (n = 25). Quercetin (Sigma, USA, dissolved in 0.9% saline solution) was administered intraperitoneally at a dose of 50 mg/kg at 30 min, 12 h, and 24 h after TBI. The neurological impairment and spatial cognitive function was assessed by the neurologic severity score and Morris water maze, respectively. Immunohistochemistry staining and western blotting was used to evaluate the expression of LC3, p-Akt, caspase-3, Bcl-2, and Bax.

Results: Quercetin treatment significantly attenuated TBI-induced neurological impairment (1–3 days, p < 0.05) and improved cognitive function (5–8 days, p < 0.05). Double immunolabeling demonstrated that quercetin significantly reduced the LC3-positive cells co-labeled with NeuN, whereas significantly enhanced p-Akt-positive cells co-labeled with NeuN. Furthermore, quercetin treatment reduced the expression of LC3、caspase-3 and Bax levels induced following TBI (p < 0.05), and increased the expression of p-Akt and Bcl-2 at 48 h (p < 0.05).

Conclusion: In conclusion, our observations indicate that post-injury treatment with quercetin could inhibit neuronal autophagy and apoptosis in the hippocampus in a rat model of TBI. The neuroprotective effects of quercetin may be related to modulation of PI3K/Akt signaling pathway.     

Communication outcome in children and adolescents with traumatic brain injury

Abstract

This article gives a brief review of investigations of speech and language impairment after paediatric traumatic brain injury (TBI) and describes possible effects of frontal lobe injury on non-aphasic disorders of communication. The relation between age and outcome after brain injury in children is also considered. Procedures for overcoming chronic obstacles to effective supports and services for students returning to school after TBI are described briefly. Although most children with normal development of language at the time of their injury experience generally satisfactory recovery of speech and language skills, there is considerable variation within this population. The most likely communication challenges relate to the socially skilled application of available speech and language skills, not their possession.     

Responsiveness and discriminant validity of the Child and Adolescent Scale of Participation across three years for children and youth with traumatic brain injury

ABSTRACT

Purpose: To examine responsiveness and discriminant validity of the Child and Adolescent Scale of Participation (CASP) across three years. Methods: Examined longitudinal data on 515 children and youth with TBI and arm injuries. Repeated measures analyses of variance were used to examine CASP scores (pre-injury; 3, 12, 24, 36 months post-injury). Results: Scores decreased from pre-injury to 3 months, but significantly only for moderate and severe TBI groups. Scores gradually increased post-injury for all groups except severe TBI. Scores were consistently lowest for severe TBI, followed by moderate TBI, mild TBI, and arm injury across time. Severe TBI scores were significantly lower than scores for mild TBI and arm injury, but not moderate TBI. Conclusions: CASP scores were responsive to change over time at most measurements and differentiated between groups, particularly severe TBI. Further research is needed with a larger sample of children with moderate/severe TBI as they were underrepresented in this study.     

Strategies of successful and unsuccessful simulators coached to feign traumatic brain injury*

Objective: The present study evaluated strategies used by healthy adults coached to simulate traumatic brain injury (TBI) during neuropsychological evaluation. Method: Healthy adults (n = 58) were coached to simulate TBI while completing a test battery consisting of multiple performance validity tests (PVTs), neuropsychological tests, a self-report scale of functional independence, and a debriefing survey about strategies used to feign TBI. Results: “Successful” simulators (n = 16) were classified as participants who failed 0 or 1 PVT and also scored as impaired on one or more neuropsychological index. “Unsuccessful” simulators (n = 42) failed ≥2 PVTs or passed PVTs but did not score impaired on any neuropsychological index. Compared to unsuccessful simulators, successful simulators had significantly more years of education, higher estimated IQ, and were more likely to use information provided about TBI to employ a systematic pattern of performance that targeted specific tests rather than performing poorly across the entire test battery. Conclusion: Results contribute to a limited body of research investigating strategies utilized by individuals instructed to feign neurocognitive impairment. Findings signal the importance of developing additional embedded PVTs within standard cognitive tests to assess performance validity throughout a neuropsychological assessment. Future research should consider specifically targeting embedded measures in visual tests sensitive to slowed responding (e.g. response time).     

Traumatic brain injury as an independent risk factor for problem gambling: a matched case-control study

Purpose

To assess whether traumatic brain injury (TBI) increases the risks of subsequent problem gambling.

Methods

We conducted a matched case–control analysis of adults in Ontario, Canada. The study included those who self-reported their gambling activities in the Canadian Community Health Survey 2007–2008. Using Problem Gambling Severity Index, we defined cases as those who were problem gamblers and controls who were recreational gamblers. Cases were matched to controls 1:2 using propensity scores based on demographics, prior mental health, and self-reported behaviours. The main predictor was prior TBI defined as requiring emergency care and identified using ICD-10 codes from administrative health databases. We estimated the likelihood of prior TBI in problem gamblers compared to controls using conditional logistic regression.

Results

Of 30,652 survey participants, 16,002 (53%) reported gambling activity of whom 14,910 (49%) were recreational gamblers and 4% (n = 1092) were problem gamblers. A total of 1469 respondents (5%) had a prior TBI. Propensity score matching yielded 2038 matched pairs with 1019 cases matched to 2037 controls. Case–control analysis showed a significant association between prior TBI and subsequent problem gambling (odds ratio 1.27, 95% confidence interval 1.07–1.51, P = 0.007). The increased risk was mostly apparent in men aged 35 to 64 years who reported alcohol use or smoking. The relative risk of problem gambling in those with two or more TBIs equated to an odds ratio of 2.04 (95% confidence interval 1.05–3.99).

Conclusions

We found that a prior TBI was associated with an increased subsequent risk of problem gambling. Our findings support more awareness, screening, and treating problem gambling risks among TBI patients.

     

Brain lesion correlates of fatigue in individuals with traumatic brain injury

ABSTRACT

The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N?=?53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N?=?36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants’ decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants’ error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.     

Reasoning training in veteran and civilian traumatic brain injury with persistent mild impairment

Traumatic brain injury (TBI) is a chronic health condition. The prevalence of TBI, combined with limited advances in protocols to mitigate persistent TBI-related impairments in higher order cognition, present a significant challenge. In this randomised study (n?=?60), we compared the benefits of Strategic Memory Advanced Reasoning Training (SMART, n?=?31), a strategy-based programme shown to improve cognitive control, versus an active learning programme called Brain Health Workshop (BHW, n?=?29) in individuals with TBI with persistent mild functional deficits. Outcomes were measured on cognitive, psychological health, functional, and imaging measures. Repeated measures analyses of immediate post-training and 3-month post-training demonstrated gains on the cognitive control domain of gist reasoning (ability to abstract big ideas/goals from complex information/tasks) in the SMART group as compared to BHW. Gains following the SMART programme were also evident on improved executive function, memory, and daily function as well as reduced symptoms associated with depression and stress. The SMART group showed an increase in bilateral precuneus cerebral blood flow (CBF). Improvements in gist reasoning in the SMART group were also associated with an increase in CBF in the left inferior frontal region, the left insula and the bilateral anterior cingulate cortex. These results add to prior findings that the SMART programme provides an efficient set of strategies that have the potential to improve cognitive control performance and associated executive functions and daily function, to enhance psychological health, and facilitate positive neural plasticity in adults with persistent mild impairment after TBI.     

Rehabilitation of executive skills post-childhood traumatic brain injury (TBI): A pilot intervention study

Background: Following TBI in childhood it is common for deficits to be seen in higher order skills, such as executive functions, both in the acute and longer-term post-injury. Despite this, very little evaluative research has been conducted with children post-TBI, particularly in the area of EF.

Methods: The current study aimed to develop and implement a pilot intervention programme for adolescent/young adults (n = 3), in the chronic phase of recovery, when EF skills are no longer in a rapid state of development.

Results and conclusions: Study results highlight the importance and need for accurate and relevant outcome measures that capture subtle as well as more obvious changes following intervention.     

The persistence of sleep disturbance and its correlates in children with moderate to severe traumatic brain injury: A longitudinal study

ObjectivesThe primary aim was to examine whether sleep disturbances persist in children in the chronic stage of recovery from moderate or severe traumatic brain injury (TBI). The secondary aim was to examine whether memory difficulties and/or other previously identified factors relate to sleep disturbances in children with moderate to severe TBI.MethodsThis longitudinal study included 21 children with moderate to severe TBI, 8–18 years old, recruited from an urban tertiary paediatric specialised brain injury rehabilitation unit. Participants were seen 5 years and again 7 years post-injury, on average. Sleep disturbances were assessed with Sleep Disturbance Scale for Children (SDSC). Correlates that were considered included indicators of TBI severity, and questionnaires assessing everyday memory, fatigue, internalizing and externalizing behaviors and pain intensity.ResultsThe SDSC scores of children with moderate to severe TBI indicated greater disturbances in initiating and maintaining sleep, arousal, sleep-wake transition, and excessive somnolence relative to the norms, at follow-up. The mean SDSC scores and the number of participants with subclinical to clinical sleep disturbances on the SDSC remained unchanged from baseline to follow-up. At follow-up, the SDSC initiating and maintaining sleep, and excessive somnolence scales were associated with poorer everyday memory and greater fatigue.ConclusionsChildren with moderate to severe TBI experience ongoing sleep disturbances for years post-injury. Greater sleep disturbances are associated with worse functional outcomes. Further research into sleep disturbances and development of treatments is important, as it could improve the outcomes of children with TBI.