Traumatic Brain Injury Injury Research Articles

Gut Microbiota as a Therapeutic Target to Ameliorate the Biochemical, Neuroanatomical, and Behavioral Effects of Traumatic Brain Injuries.

Current efficacious treatments for traumatic brain injury (TBI) are lacking. Establishment of a protective gut microbiota population offers a compelling therapeutic avenue, as brain injury induces disruptions in the composition of the gut microbiota, i.e., gut dysbiosis, which has been shown to contribute to TBI-related neuropathology and impaired behavioral outcomes. The gut microbiome is involved in the modulation of a multitude of cellular and molecular processes fundamental to the progression of TBI-induced pathologies including neuroinflammation, blood brain barrier permeability, immune system response, microglial activation, and mitochondrial dysfunction, as well as intestinal motility and permeability. Additionally, gut dysbiosis further aggravates behavioral impairments in animal models of TBI and spinal cord injury, as well as negatively affects health outcomes in murine stroke models. Recent studies indicate that microbiota transplants and probiotics ameliorate neuroanatomical damage and functional impairments in animal models of stroke and spinal cord injury. In addition, probiotics have been shown to reduce the rate of infection and time spent in intensive care of hospitalized patients suffering from brain trauma. Perturbations in the composition of the gut microbiota and its metabolite profile may also serve as potential diagnostic and theragnostic biomarkers for injury severity and progression. This review aims to address the etiological role of the gut microbiome in the biochemical, neuroanatomical, and behavioral/cognitive consequences of TBI, as well as explore the potential of gut microbiome manipulation in the form of probiotics as an effective therapeutic to ameliorate TBI-induced pathology and symptoms.

Fall-related traumatic brain injury in children ages 0–4 years

Introduction: Falls are the leading cause of traumatic brain injury (TBI) for children in the 0–4 year age group. There is limited literature pertaining to fall-related TBIs in children age 4 and under and the circumstances surrounding these TBIs. This study provides a national estimate and describes actions and products associated with fall-related TBI in this age group. Method: Data analyzed were from the 2001–2013 National Electronic Injury Surveillance System–All Injury Program (NEISS–AIP), a nationally representative sample of emergency departments (ED). Case narratives were coded for actions associated with the fall, and product codes were abstracted to determine fall location and product type. All estimates were weighted. Results: An estimated 139,001 children younger than 5 years were treated annually in EDs for nonfatal, unintentional fall-related TBI injuries (total = 1,807,019 during 2001–2013). Overall, child actions (e.g., running) accounted for the greatest proportion of injuries and actions by others (e.g., carrying) was highest for children younger than 1 year. The majority of falls occurred in the home, and involved surfaces, fixtures, furniture, and baby products. Conclusions: Fall-related TBI in young children represents a significant public health burden. The majority of children seen for TBI assessment in EDs were released to home. Prevention efforts that target parent supervision practices and the home environment are indicated. Practical applications: Professionals in contact with parents of young children can remind them to establish a safe home and be attentive to the environment when carrying young children to prevent falls.

Traumatic Brain Injury Results in Dynamic Brain Structure Changes Leading to Acute and Chronic Motor Function Deficits in a Pediatric Piglet Model

Traumatic brain injury (TBI) is a leading cause of death and disability in children. Pediatric TBI patients often suffer from crippling cognitive, emotional, and motor function deficits that have negative lifelong effects. The objective of this study was to longitudinally assess TBI pathophysiology using multi-parametric magnetic resonance imaging (MRI), gait analysis, and histological approaches in a pediatric piglet model. TBI was produced by controlled cortical impact in Landrace piglets. MRI data, including from proton magnetic resonance spectroscopy (MRS), were collected 24 hours and 12 weeks post-TBI, and gait analysis was performed at multiple time-points over 12 weeks post-TBI. A subset of animals was sacrificed 24 hours, 1 week, 4 weeks, and 12 weeks post-TBI for histological analysis. MRI results demonstrated that TBI led to a significant brain lesion and midline shift as well as microscopic tissue damage with altered brain diffusivity, decreased white matter integrity, and reduced cerebral blood flow. MRS showed a range of neurochemical changes after TBI. Histological analysis revealed neuronal loss, astrogliosis/astrocytosis, and microglia activation. Further, gait analysis showed transient impairments in cadence, cycle time, % stance, step length, and stride length, as well as long-term impairments in weight distribution after TBI. Taken together, this study illustrates the distinct time course of TBI pathoanatomic and functional responses up to 12 weeks post-TBI in a piglet TBI model. The study of TBI injury and recovery mechanisms, as well as the testing of therapeutics in this translational model, are likely to be more predictive of human responses and clinical outcomes compared to traditional small animal models.

Genetic Influences on Behavioral Outcomes After Childhood TBI: A Novel Systems Biology-Informed Approach.

Objectives: To test whether genetic associations with behavioral outcomes after early childhood traumatic brain injury (TBI) are enriched for biologic pathways underpinning neurocognitive and behavioral networks.Design: Cross-sectional evaluation of the association of genetic factors with early (~ 6 months) and long-term (~ 7 years) post-TBI behavioral outcomes. We combined systems biology and genetic association testing methodologies to identify biologic pathways associated with neurocognitive and behavior outcomes after TBI. We then evaluated whether genes/single nucleotide polymorphism (SNPs) associated with these biologic pathways were more likely to demonstrate a relationship (i.e., enrichment) with short and long-term behavioral outcomes after early childhood TBI compared to genes/SNPs not associated with these biologic pathways.Setting: Outpatient research setting.Participants:140 children, ages 3–6:11 years at time of injury, admitted for a TBI or orthopedic injury (OI).Interventions: Not Applicable.Main Outcome Measures: Child behavior checklist total problems T score.Results: Systems biology methodology identified neuronal systems and neurotransmitter signaling (Glutamate receptor, dopamine, serotonin, and calcium signaling), inflammatory response, cell death, immune systems, and brain development as important biologic pathways to neurocognitive and behavioral outcomes after TBI. At 6 months post injury, the group (TBI versus OI) by polymorphism interaction was significant when the aggregate signal from the highest ranked 40% of case gene associations was compared to the control set of genes. At ~ 7 years post injury, the selected polymorphisms had a significant main effect after controlling for injury type when the aggregate signal from the highest ranked 10% of the case genes were compared to the control set of genesConclusions: Findings demonstrate the promise of applying a genomics approach, informed by systems biology, to understanding behavioral recovery after pediatric TBI. A mixture of biologic pathways and processes are associated with behavioral recovery, specifically genes associated with cell death, inflammatory response, neurotransmitter signaling, and brain development. These results provide insights into the complex biology of TBI recovery.

Consolidated Biochemical Profile of Subacute Stage Traumatic Brain Injury in Early Development.

Traumatic brain injury (TBI) in general has varied neuropathological consequences depending upon the intensity and biomechanics of the injury. Furthermore, in pediatric TBI, intrinsic developmental changes add further complexity, necessitating a biochemical dimension for improved TBI characterization. In our earlier study investigating the subacute stage TBI metabolome (72 h post-injury) in a developmental rat model, significant ipsilateral brain biochemical changes occurred across 25 metabolite sets as determined by metabolite set enrichment analysis (MSEA). The broad metabolic perturbation was accompanied by behavioral deficits and neuronal loss across the ipsilateral hemisphere containing the injury epicenter. In order to obtain a consolidated biochemical profile of the TBI assessment, a subgrouping of the 190 identified brain metabolites was performed. Metabolites were divided into seven major subgroups: oxidative energy/mitochondrial, glycolysis/pentose phosphate pathway, fatty acid, amino acid, neurotransmitters/neuromodulators, one-carbon/folate and other metabolites. Subgroups were based on the chemical nature and association with critically altered biochemical pathways after TBI as obtained from our earlier untargeted analysis. Each metabolite subgroup extracted from the ipsilateral sham and TBI brains were modeled using multivariate partial least square discriminant analysis (PLS-DA) with the model accuracy used as a measurable index of TBI neurochemical impact. Volcano plots of each subgroup, corrected for multiple comparisons, determined the TBI neurochemical specificity. The results provide a ranked biochemical profile along with specificity of changes after developmental TBI, enabling a consolidated biochemical template for future classification of different TBI intensities and injury types in animal models.

Plasma Tau and Amyloid Are Not Reliably Related to Injury Characteristics, Neuropsychological Performance, or White Matter Integrity in Service Members with a History of Traumatic Brain Injury.

The aim of this study was to examine the relationship between plasma tau and amyloid beta-42 (Aβ42), neuropsychological functioning, and white matter integrity in U.S. military service members with (n = 155) and without (n = 42) a history of uncomplicated mild (n = 83), complicated mild (n = 26), or moderate, severe, or penetrating (n = 46) traumatic brain injury (TBI). We hypothesized that higher levels of tau and Aβ42 would be related to reduced neurocognitive performance and white matter integrity. Participants were enrolled prospectively from Walter Reed National Military Medical Center. Participants completed a blood draw, neuropsychological assessment, and diffusion tensor imaging (General Electric 3T) of the whole brain. From 20 neuropsychological test scores, five cognitive domain scores were computed. Measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated for 18 regions of interest (ROIs). There was no relationship found between the plasma biomarkers and neurocognitive performance in any of the three TBI groups (all ps >0.05; all R2 changes <0.146). Although not reaching statistical significance after correction for multiple comparisons, higher tau and Aβ42 tended to be related to higher FA and lower MD, RD, and AD in patients with a history of moderate, severe, or penetrating TBI. There was no consistent relationship between either of the biomarkers and white matter integrity in the complicated and uncomplicated mild TBI groups. In addition, there was no significant relationship between the biomarkers and age, education, sex, race, bodily injury severity, time since injury, TBI severity, or number of TBIs (all ps >0.15). Future investigation in larger samples of moderate, severe, and penetrating TBI are needed. Other plasma biomarkers, including phosphorylated tau, exosomal tau, and interleukin-10, may be more promising measures to use in the diagnosis, management, and treatment of TBI.

Noninvasive magnetic resonance imaging stratifies injury severity in a rodent model of male juvenile traumatic brain injury.

Age and severity are significant predictors of traumatic brain injury (TBI) outcomes in the immature brain. TBI studies have segregated TBI injury into three severity groups: mild, moderate, and severe. While mild TBI is most frequent form in children and adults, there is debate over the indicators used to denote mild injury. Clinically, magnetic resonance imaging (MRI) and computed tomography (CT) are used to diagnose the TBI severity when medically warranted. Herein, we induced mild, moderate, and severe TBI in juvenile rats (jTBI) using the controlled cortical impact model. We characterized the temporal and spatial injury after graded jTBI in vivo using high-field MRI at 0.25 (6hr), 1 and 3days post-injury (dpi) with comparative histology. Susceptibility-weighted imaging (SWI) for blood and T2-weighted imaging (T2WI) for edema were quantified over the 0.25-3 dpi. Edema volumes increased linearly with severity at 0.25 dpi that slowly continued to decrease over the 3 dpi. In contrast, blood volumes did not decrease over time. Mild TBI had the least amount of blood visible on SWI. Fluoro-jade B (FJB) staining for cell death confirmed increased cellular death with increasing severity and increased FJB+cells in the corpus callosum (CC). Interestingly, the strongest correlation was observed for cell death and the presence of extravascular blood. A clear understanding of acute brain injury (jTBI) and how blood/edema contribute to mild, moderate, and severe jTBI is needed prior to embarking on therapeutic interventions. Noninvasive imaging should be used in mild jTBI to verify lack of overt injury.

Extraventricular Drainage as First-Tier Management of Raised Intracranial Pressure After Severe Pediatric Trauma Brain Injury

Objective - To present the most efficatious management of raised intracranial pressure after severe trauma brain injury in a pediatric patient. Case report - A 5-year-old Caucasian presented to the emergency room due to head injury caused by falling down stairs. At the time of admission the patient was comatose with pediatric Glasgow Coma Score 6 (V-1, E-1, M-4) and signs of recent posterior head trauma. Computed tomography (CT) scan showed a multifragmented fracture of the occipital bone above the “sinus lake” causing an epidural mass, contusion in the right cerebellar hemisphere, a skull base fracture without signs of midline shifting. Six hours later, during monitoring in the intensive care unit, the patient became cardiorespiratory unstable with signs of uncal brain herniation and Cushing’s triad. Control CT revealed previously verified posttraumatic changes with new signs of decompensating internal hydrocephalus. Considering that evacuation of the epidural collection and decompression of impaired bone fragments in the area of the “sinus lake” would be too risky, extraventricular drainage as the first tier management was properly selected as the option of treatment. Taking into account the hazard / benefit ratio it was shown to be the most effective form of treatment, which was confirmed after six-month follow-up without any form of neurocognitive impairment. Conclusion – Treatment of traumatic brain injury (TBI) in the pediatric population requires a multidisciplinary approach. Different mechanisms of pediatric TBI injury vary widely by age groups and its impact on the development of primary and secondary brain lesions differs. Although many general principles of managing pediatric TBI are similar to adults, cerebral plasticity is one of the features which ultimately always leaves space for a better final outcome of treatment.

Traumatic brain injuries in New Zealand: National Insurance (Accident Compensation Corporation) claims from 2012 to 2016

AimTo provide epidemiological data and related costs to the national health insurance scheme for traumatic brain injury (TBI) in New Zealand. MethodA retrospective analytical review utilising detailed descriptive minor and moderate-to-severe epidemiological TBI data obtained from the Accident Compensation Corporation (ACC) for 2012–2016. Injuries were analysed by three levels of increasing severity: moderate, moderate-to-serious (MSC) and severe claims categories. ResultsOver the January 2012 to December 2016 period there were 97,955 claims for TBI costing ACC $1,450,643,667 [equivalent to £$743,417,120]. Falls accounted for nearly half (41.7%, 8262), and over a quarter (39.9%; $67,626,000 [£34,662,176]) of the moderate claims for TBI. Motor vehicle accidents recorded the highest percentage (36.5%), total costs ($610,978,229 [£313,170,000]) and highest mean cost per-moderate claim per-year ($47,372 ± $2401 [£24,282 ± £1231]) for MSC TBI claims. This was similar for severe claims where motor vehicles accidents accounted for 56% of the total serious claims, 65.1% of the costs with a mean cost per-serious claim of $64,913 ± 4331 [£32,759 ± £2186] per-year. ConclusionThere were 97,955 TBI injury claims lodged over the duration of the study with 36% (n = 35,304) classified as MSC. The incidence of total TBI in New Zealand was 432 per 100,000 population, and 155 per 100,000 for MSC TBI claims. Despite the growing number of studies reporting on the effects of sports-related TBI, there is a paucity of studies reporting on the longitudinal effects of TBI in falls, assaults and motor vehicle accidents. Further research is warranted into the assessment and management of intimate partner violence and child abuse victims for TBI's.

The overlooked aspect of excitotoxicity: Glutamate-independent excitotoxicity in traumatic brain injuries.

Traumatic brain injury (TBI) is a leading major cause of morbidity and mortality in youth and individuals under 45year age. A wide variety of cellular and molecular mechanisms have been identified contributing to the pathogenesis of TBI. A better understanding of the pathophysiology behind TBI is essential for providing more effective treatment. Excitotoxicity as one of the secondary molecular events is a major contributing factor in apoptosis and neuronal death following the initial injury in TBI. Excitotoxicity is the rapid overload and influx of calcium into the cell cytoplasm, activating a series of deleterious signaling cascades causing the cell to undergo apoptosis. Conventional understanding is that the rapid influx of calcium is initiated through glutamate release. However, there are overlooked glutamate-independent mechanisms that cause the rapid calcium influx into the neuronal cytoplasm, evoking or contributing to excitotoxicity. Therefore, the focus of this review will be on the role of the glutamate-independent excitotoxic mechanisms of the mechanosensitive response of NMDA receptors, mechanoporation of the cell membrane, ischemia, and the release of calcium from intracellular stores. In conclusion, the shear and stretch forces during a TBI event may result in the mechanosensitive activation of NMDA receptors which contribute to glutamate-independent excitotoxicity.

A retrospective review of patients with significant traumatic brain injury transported by emergency medical services within the south east of England.

Introduction:Traumatic brain injury (TBI) will be a leading cause of death and disability within the Western world by 2020. Currently, 80% of all TBI patients in England are transported to hospital by an ambulance service. The aim of this retrospective study is to compare TBI patients transported to a major trauma centre (MTC) against those transported to a trauma unit (TU).Method:All patients with a primary injury of TBI who were transported to hospital by South East Coast Ambulance Service NHS Foundation Trust (SECAmb) from 1 January 2016 to 31 December 2016 and entered into the Trauma Audit & Research Network (TARN) registry were reviewed. Patients were stratified by hospital designation (MTC or TU). Severity of TBI was categorised using the patients’ pre-hospital Glasgow Coma Scale (GCS) and Abbreviated Injury Score (AIS) Head. The outcomes of interest were 30-day mortality and Glasgow Outcome Score (GOS) at discharge.Results:Between 1 January and 31 December 2016, 549 TBI patients were identified in the TARN database as being transported by SECAmb to either an MTC or a TU. The majority of patients were transported to a TU (77.96%), and the median age of the TU cohort was older than the MTC group (TU 82.15 IQR 16.73 vs. MTC 62.1 IQR 42.6). The median Injury Severity Score (ISS) was greater in the MTC cohort (22 IQR 10 vs. 17 IQR 9), where falls from height and road traffic collisions (RTCs) contributed to 50.51% of all injuries. Within the TU cohort, falls from less than 2 metres (standing height) were the main mechanism of injury (MOI) (77.62%). The median length of hospital stay (LOS) was longer in the MTC cohort compared to the TU cohort (10 IQR 13.25 vs. 8 IQR 14).Conclusion:The high proportion of mild TBI and absence of reliable triage guidelines make it difficult for ambulance clinicians to identify patients who will benefit from transport to an MTC. Future research should focus on how TBI triage influences outcomes and how ambulance services can better identify patients with a TBI and who would benefit from specialist care.

The pig as a preclinical traumatic brain injury model: current models, functional outcome measures, and translational detection strategies.

Traumatic brain injury (TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.

Diagnosis, monitoring and prognosis of secondary brain damage in icu patients with traumatic brain injuries

Traumatic brain injury (TBI) is the brain injury that occurs whenever a physical force that impacts the head leads to neuropathology. The types of primary TBI are penentrating TBI or non-penetrating TBI and it can lead to intracerebral contusions, hemorrhages or extra-axial hematomas. Patients with TBI can also have skull fractures or concussions. The injury severity can be classified in many ways but the most established and common used is the Glascow Coma Scale (GCS). However, with the GCS, each of the severity criteria has limitations and might mot be an accurate predictor of TBI severity and outcome when used alone. For this reason it is often used in conjunction with other parameters (Abbreviated Injury Scale - AIS). Secondary Brain Damage is the injury that occurs to the TBI patient not at the time of the accident, but during the following minutes, hours or days. There are many mechanisms that lead to development of cerebral edema, blood-brain barrier disruption, vasospasm, increase in volume of bleeding, contusions and intracranial hypertension. These mechanisms can act either in cellular level or systemic level. The cellular mechanisms that lead to secondary brain damage include necrosis or apoptosis, mitochondrial dysfunction, excitotoxicicty, formation of free radicals, changes in cerebral glucose metabolism and inflammation. The mechanisms at systemic level include hypoxia-cerebral oxygenation, hypo or hypertension, hypo or hyper-capnia, anemia, hyponatremia and hyper or hypoglycemia. The first tool to diagnose severe TBI and secondary brain injury is neurological assessment. Neuroimaging is one of the most important ways for diagnosis. Computed Tomography (CT scan), Magnetic Resonance Imaging (MRI), cerebral angiography, transcranial Doppler, CT perfusion, Xenon CT, MRI diffusion, MRI perfusion, MRI spectrometry and Positron Emission Tomography (PET) are possible ways of imaging that not only help in the diagnosis but give important information that help in choosing the correct management. Moreover, neuromonitoring, helps in the correct management of the patient.

Book Review : NEUROTRAUMA AND CRITICAL CARE OF THE BRAIN

Traumatic Brain Injury (TBI) is one of the leading cause of death and disability. TBI and spinal cord injuries have impacts on patients life, their families and also to the comunity. This edition retained the book structure of the first edition with emphasis in critical care and also it offers review the updated guideline recommendation. A review gives the reader not only summary of the content but also a critical assesment about the content. Additionally, this book gives the reader content about a brief review of a basic ethical framework. The concern is not only about science but also about prehospital care, critical care, outcome, ethical issue, prevention and sosioeconomic.

External validation of the Scandinavian guidelines for management of minimal, mild and moderate head injuries in children

BackgroundClinical decision rules (CDRs) aid in the management of children with traumatic brain injury (TBI). Recently, the Scandinavian Neurotrauma Committee (SNC) has published practical, evidence-based guidelines for children with Glasgow Coma Scale (GCS) scores of 9–15. This study aims to validate these guidelines and to compare them with other CDRs.MethodsA large prospective cohort of children (< 18 years) with TBI of all severities, from ten Australian and New Zealand hospitals, was used to assess the SNC guidelines. Firstly, a validation study was performed according to the inclusion and exclusion criteria of the SNC guideline. Secondly, we compared the accuracy of SNC, CATCH, CHALICE and PECARN CDRs in patients with GCS 13–15 only. Diagnostic accuracy was calculated for outcome measures of need for neurosurgery, clinically important TBI (ciTBI) and brain injury on CT.ResultsThe SNC guideline could be applied to 19,007/20,137 of patients (94.4%) in the validation process. The frequency of ciTBI decreased significantly with stratification by decreasing risk according to the SNC guideline. Sensitivities for the detection of neurosurgery, ciTBI and brain injury on CT were 100.0% (95% CI 89.1–100.0; 32/32), 97.8% (94.5–99.4; 179/183) and 95% (95% CI 91.6–97.2; 262/276), respectively, with a CT/admission rate of 42% (mandatory CT rate of 5%, 18% CT or admission and 19% only admission). Four patients with ciTBI were missed; none needed specific intervention. In the homogenous comparison cohort of 18,913 children, the SNC guideline performed similar to the PECARN CDR, when compared with the other CDRs.ConclusionThe SNC guideline showed a high accuracy in a large external validation cohort and compares well with published CDRs for the management of paediatric TBI.

Inhibition of NADPH Oxidase Activation by Apocynin Rescues Seizure-Induced Reduction of Adult Hippocampal Neurogenesis.

Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. Apocynin is known to be an inhibitor of NADPH (Nicotinamide adenine dinucleotide phosphate) oxidase activity and is highly effective in suppressing the production of superoxide. The neuroprotective effects of apocynin have been investigated in numerous brain injury settings, such as stroke, traumatic brain injury (TBI), and epilepsy. Our lab has demonstrated that TBI or seizure-induced oxidative injury and neuronal death were reduced by apocynin treatment. Several studies have also demonstrated that neuroblast production is transiently increased in the hippocampus after seizures. Here, we provide evidence confirming the hypothesis that long-term treatment with apocynin may enhance newly generated hippocampal neuronal survival by reduction of superoxide production after seizures. A seizure was induced by pilocarpine [(25 mg/kg intraperitoneal (i.p.)] injection. Apocynin was continuously injected for 4 weeks after seizures (once per day) into the intraperitoneal space. We evaluated neuronal nuclear antigen (NeuN), bromodeoxyuridine (BrdU), and doublecortin (DCX) immunostaining to determine whether treatment with apocynin increased neuronal survival and neurogenesis in the hippocampus after seizures. The present study indicates that long-term treatment of apocynin increased the number of NeuN+ and DCX+ cells in the hippocampus after seizures. Therefore, this study suggests that apocynin treatment increased neuronal survival and neuroblast production by reduction of hippocampal oxidative injury after seizures.

Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets.

Traumatic Brain Injury (TBI) is the most frequent cause of death and disability in young adults and children in the developed world, occurring in over 1.7 million persons and resulting in 50,000 deaths in the United States alone. The Centers for Disease Control and Prevention estimate that between 3.2 and 5.3 million persons in the United States live with a TBI-related disability, including several neurocognitive disorders and functional limitations. Following the primary mechanical injury in TBI, literature suggests the presence of a delayed secondary injury involving a variety of neuroinflammatory changes. In the hours to days following a TBI, several signaling molecules and metabolic derangements result in disruption of the blood-brain barrier, leading to an extravasation of immune cells and cerebral edema. The primary, sudden injury in TBI occurs as a direct result of impact and therefore cannot be treated, but the timeline and pathophysiology of the delayed, secondary injury allows for a window of possible therapeutic options. The goal of this review is to discuss the pathophysiology of the primary and delayed injury in TBI as well as present several preclinical studies that identify molecular targets in the potential treatment of TBI. Additionally, certain recent clinical trials are briefly discussed to demonstrate the current state of TBI investigation.

Parenting Behaviors after Moderate – Severe Traumatic Injury in Early Childhood

ABSTRACTPurpose: Examine the impact of traumatic brain injury (TBI) on parenting behavior over time.Method: Included 206 children (3–7 years old) with moderate to severe TBI or orthopedic injury, using a prospective longitudinal cohort study design. Assessments completed at baseline, 6-months, 12-months, 18-months, 3.5 years, and 6.8 years after injury. Dependent variables included authoritative, permissive, and authoritarian parenting.Results: Injury characteristics had limited impact on parenting behaviors over time. Levels of authoritative parenting remained stable over time; however, levels of warmth and involvement declined over time for those with TBI. Levels of permissive and authoritarian parenting declined for all participants by 3.5 years post injury. SES and stressors impacted parenting behaviors.Conclusions: While there was limited effect of TBI on parenting behavior over time, it remains unclear how individuals respond to these parenting behaviors years after injury. Clinicians should monitor family and parenting behaviors to foster an environment to promote positive recovery.

Longitudinal Developmental Outcomes after Traumatic Brain Injury in Young Children: Are Infants More Vulnerable Than Toddlers?

Children under 4 years of age have the highest incidence of traumatic brain injury (TBI) among the non-elderly and may be at high risk of poor developmental outcomes. We prospectively enrolled a cohort of children injured before 31 months old with TBI or orthopedic injury (OI), from 2013 to 2015 at two pediatric level 1 trauma centers to study very young children's developmental outcomes after injury. We used Ages & Stages-3 and Ages & Stages: Social-Emotional screening tools to measure children's development at pre-injury and 3 and 12 months post-injury. The cohort included 123 children with TBI categorized as mild (n = 48), complicated-mild or moderate (n = 54), and severe (n = 21) and 45 children with OI. Generalized linear models examined effects of injury severity and age at injury controlling for pre-injury ratings. Children with mild or complicated-mild/moderate TBI generally remained on developmental track. Compared to OI, children with severe TBI tended to have a negative developmental trajectory with decrements in communication (-7.07; 95% confidence interval [CI], -13.7, -0.48), gross motor (-15.2; 95% CI, -21.1, -9.19), problem solving (-11.6; 95% CI, -17.9, -5.29), personal-social (-16.8; 95% CI, -22.8, -10.8), and social-emotional (21.0; 95% CI, 7.32, 34.7) domains 12 months post-injury. Developmental effects from TBI differed by age at injury: Infants had more difficulties than older children in communication and problem-solving domains. Despite low developmental scores in 28% of the cohort, only 5% were receiving Early Childhood Intervention (ECI) services 12 months after injury. Early age at injury is a vulnerability factor after TBI. Young age and severe injury should prompt evaluation for ECI.

Histology of Brain Trauma and Hypoxia-Ischemia.

Forensic pathologists encounter hypoxic-ischemic (HI) brain damage or traumatic brain injuries (TBI) on an almost daily basis. Evaluation of the findings guides decisions regarding cause and manner of death. When there are gross findings of brain trauma, the cause of death is often obvious. However, microscopic evaluation should be used to augment the macroscopic diagnoses. Histology can be used to seek evidence for TBI in the absence of gross findings, e.g., in the context of reported or suspected TBI. Estimating the survival interval after an insult is often of medicolegal interest; this requires targeted tissue sampling and careful histologic evaluation. Retained tissue blocks serve as forensic evidence and also provide invaluable teaching and research material. In certain contexts, histology can be used to demonstrate nontraumatic causes of seemingly traumatic lesions. Macroscopic and histologic findings of brain trauma can be confounded by concomitant HI brain injury when an individual survives temporarily after TBI. Here we review the histologic approaches for evaluating TBI, hemorrhage, and HI brain injury. Amyloid precursor protein (APP) immunohistochemistry is helpful for identifying damaged axons, but patterns of damage cannot unambiguously distinguish TBI from HI. The evolution of hemorrhagic lesions will be discussed in detail; however, timing of any lesion is at best approximate. It is important to recognize artifactual changes (e.g., dark neurons) that can resemble HI damage. Despite the shortcomings, histology is a critical adjunct to the gross examination of brains.