Elucidating PAR1 as a therapeutic target for delayed traumatic brain injury: Unveiling the PPAR-γ/Nrf2/HO-1/GPX4 axis to suppress ferroptosis and alleviate NLRP3 inflammasome activation in rats.

Repetitive traumatic brain injury (RTBI) is acknowledged as a silent overlooked public health crisis, with an incomplete understanding of its pathomechanistic signaling pathways. Mounting evidence suggests the involvement of thrombin and its receptor, the protease-activated receptor (PAR)1, in the development of secondary injury in TBI; however, the consequences of PAR1 modulation and its impact on ferroptosis-redox signaling, and NLRP3 inflammasome activation in RTBI, remain unclear. Further, the utilitarian function of PAR1 as a therapeutic target in RTBI has not been elucidated. To study this crosstalk, RTBI was induced in Wistar rats by daily weight drops on the right frontal region for five days. Three groups were included: normal control, untreated RTBI, and RTBI+SCH79797 (a PAR1 inhibitor administered post-trauma at 25 µg/kg/day). The concomitant treatment of PAR1 antagonism improved altered behavior function, cortical histoarchitecture, and neuronal cell survival. Moreover, the receptor blockade downregulated mRNA expression of PAR1 but upregulatedthat of the neuroprotective receptor PPAR-γ. The anti-inflammatory impact of SCH79797 was signified by the low immune expression/levels of NF-κB p65,TNF-α, IL-1ß, and IL-18. Consequently, the PAR1 blocker hindered the formation of inflammasome components NLRP3, ASC, and activated caspase-1. Ultimately, SCH79797 treatment abated ferroptosis-dependent iron redox signaling through the activation of the antioxidant Nrf2/HO-1 axis and its subsequent antioxidant machinery (GPX4, SOD) to limit lipid peroxidation, iron accumulation, and transferrin serum increment. Collectively, SCH79797 offered putative preventive mechanisms against secondary RTBI consequences in rats by impeding ferroptosis and NLRP3 inflammasome through activating the PPAR-γ/Nrf2 antioxidant cue.

Intramyelinic edema manifesting as central white matter diffusion restriction associated with brain contusion in pediatric patients.

In traumatic brain injury, white matter diffusion restriction can be an imaging manifestation of non-hemorrhagic axonal injury. In this article, a different pattern of widespread white matter diffusion restriction associated with ipsilateral cortical damage, all noted in pediatric and young adult TBI patients, is presented. Its atypical pattern of distribution and extensive scope on imaging suggest excitotoxicity and intramyelinic edema as possible underlying mechanisms.

Usefulness of Artificial Intelligence in Traumatic Brain Injury: A Bibliometric Analysis and Mini-review.

BACKGROUND: Traumatic brain injury (TBI) has become a major source of disability worldwide, increasing the interest in algorithms that use artificial intelligence (AI) to optimize the interpretation of imaging studies, prognosis estimation, and critical care issues. In this study we present a bibliometric analysis and mini-review on the main uses that have been developed for TBI in AI. METHODS: The results informing this review come from a Scopus database search as of April 15, 2023. The bibliometric analysis was carried out via the mapping bibliographic metrics method. Knowledge mapping was made in the VOSviewer software (V1.6.18), analyzing the "link strength" of networks based on co-occurrence of key words, countries co-authorship, and co-cited authors. In the mini-review section, we highlight the main findings and contributions of the studies. RESULTS: A total of 495 scientific publications were identified from 2000 to 2023, with 9262 citations published since 2013. Among the 160 journals identified, The Journal of Neurotrauma, Frontiers in Neurology, and PLOS ONE were those with the greatest number of publications. The most frequently co-occurring key words were: "machine learning", "deep learning", "magnetic resonance imaging", and "intracranial pressure". The United States accounted for more collaborations than any other country, followed by United Kingdom and China. Four co-citation author clusters were found, and the top 20 papers were divided into reviews and original articles. CONCLUSIONS: AI has become a relevant research field in TBI during the last 20 years, demonstrating great potential in imaging, but a more modest performance for prognostic estimation and neuromonitoring.

A meta-analysis of cognitive and functional outcomes in severe brain trauma cases.

Background: Severe traumatic brain injuries (TBIs) are an important health issue worldwide, which are associated with harmful side effects. This meta-analysis investigates the cognitive and functional outcomes in severe brain trauma cases. It assesses the impact on memory, verbal and visual abilities, attention, learning, and the presence of depression. The study provides a comprehensive overview of the consequences of severe brain trauma injury on cognitive and functional domains. Objective: The main objective of the current comprehensive meta-analysis study is to assess and analyze the impact of severe TBI on functional and cognitive outcomes, including verbal, visual, attention, learning, memory, and emotional stability. Methods: We collected data from three online databases, including PubMed, Cochrane Library, and Embase. Case-control trials related to severe TBI association with cognitive and functional outcomes were included. Verbal strength, visual functions, learning abilities, attention, memory, and depression were considered primary outcomes. Results: We have included 13 case-control studies with 1,442 subjects in this meta-analysis, which provide adequate data to determine the pooled effect size for targeted outcomes. The effect of severe TBI on the inducement of depression and impairment of memory, verbal, visual, attention, and learning abilities compared to the control group showed statistically significant outcomes (p < 0.05). Conclusion: Severe TBI is strongly associated with impaired cognitive and functional abilities, including visual and verbal disabilities, impaired memory, depression inducement, attention deficits, and learning disabilities.

A Case of Transient Hyperlactatemia Induced by Intravenous Glycerol Administration in a Patient With Brain Trauma.

Elevated lactate levels are associated with a poor prognosis in patients with sepsis and shock. Intravenous glycerol administration is often used in Japan to treat patients with acute stroke or brain trauma, but such treatment can cause elevated lactate levels. We experienced a case of transient hyperlactatemia induced by intravenous glycerol administration in a patient with brain trauma. A 74-year-old woman underwent decompressive craniotomy because of loss of consciousness and brain edema. Glycerol was administered after the operation for management of the brain edema. Although the patient's hemodynamics remained stable, her lactate level decreased and increased repeatedly. We recognized that the elevation in her lactate level was associated with the administration of intravenous glycerol. This case suggests that intravenous glycerol administration can induce transient hyperlactatemia.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

BACKGROUND: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. METHODS: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. RESULTS: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. CONCLUSIONS: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

Head injury: Importance of the deep brain nuclei in force transmission to the brain.

Finite element modeling provides a digital representation of the human body. It is currently the most pertinent method to study the mechanisms of head injury, and is becoming a scientific reference in forensic expert reports. Improved biofidelity is a recurrent aim of research studies in biomechanics in order to improve earlier models whose mechanical properties conformed to simplified elastic behavior and mechanic laws. We aimed to study force transmission to the brain following impacts to the head, using a finite element head model with increased biofidelity. To the model developed by the Laboratory of Applied Biomechanics of Marseille, we added new brain structures (thalamus, central gray nuclei and ventricular systems) as well as three tracts involved in the symptoms of head injury: the corpus callosum, uncinate tracts and corticospinal tracts. Three head impact scenarios were simulated: an uppercut with the prior model and an uppercut with the improved model in order to compare the two models, and a lateral impact with an impact velocity of 6.5 m/s in the improved model. In these conditions, in uppercuts the maximum stress values did not exceed the injury risk threshold. On the other hand, the deep gray matter (thalamus and central gray nuclei) was the region at highest risk of injury during lateral impacts. Even if injury to the deep gray matter is not immediately life-threatening, it could explain the chronic disabling symptoms of even low-intensity head injury.

Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of pathological structures, but they have produced many contradictory findings. Since correctly identifying the underlying neuroanatomical changes is critical to advancing TBI research, we compared three commonly used markers for their ability to detect TBI pathological structures: Fluoro-Jade C, the rabbit monoclonal antibody Y188 against amyloid precursor protein and the NeuroSilver kit were used to stain adjacent slices from naïve or injured mouse brains harvested at different time points from 30 min to 3 months after lateral fluid percussion injury. Although not all pathological structures were stained by all markers at all time points, we found damaged neurons and deformed dendrites in gray matter, punctate and perivascular structures in white matter, and axonal blebs and Wallerian degeneration in both gray and white matter. The present study demonstrates the temporal and structural sensitivities of the three biomarkers: each marker is highly effective for a set of pathological structures, each of which in turn emerges at a particular time point. Furthermore, the different biomarkers showed different abilities at detecting identical types of pathological structures. In contrast to previous studies that have used a single biomarker at a single time range, the present report strongly recommends that a combination of different biomarkers should be adopted and different time points need to be checked when assessing neuropathology after TBI.

Biosubstitutes for dural closure: Unveiling research, application, and future prospects of dura mater alternatives.

The dura mater, as the crucial outermost protective layer of the meninges, plays a vital role in safeguarding the underlying brain tissue. Neurosurgeons face significant challenges in dealing with trauma or large defects in the dura mater, as they must address the potential complications, such as wound infections, pseudomeningocele formation, cerebrospinal fluid leakage, and cerebral herniation. Therefore, the development of dural substitutes for repairing or reconstructing the damaged dura mater holds clinical significance. In this review we highlight the progress in the development of dural substitutes, encompassing autologous, allogeneic, and xenogeneic replacements, as well as the polymeric-based dural substitutes fabricated through various scaffolding techniques. In particular, we explore the development of composite materials that exhibit improved physical and biological properties for advanced dural substitutes. Furthermore, we address the challenges and prospects associated with developing clinically relevant alternatives to the dura mater.

E-scooter accidents-epidemiology and injury patterns: 3-year results from a level 1 trauma center in Germany.

INTRODUCTION: Since the introduction of e-scooters in Germany in 2019, they are becoming more and more popular and associated injuries have increased significantly. The aim of this study was to assess the injury patterns after e-scooter accidents. MATERIALS AND METHODS: From May 2019 to October 2022, all consecutive patients who presented at our emergency department (ED) following e-scooter accidents were included in our study and retrospectively analyzed. RESULTS: A total of 271 patients were included in our study. The mean age was 33 years. 38% of the patients were female and 62% were male. Most common injuries were traumatic brain injuries in 38% of the patients together with fractures affecting the upper limb (17%). An operative treatment was necessary in 40 patients. Most of the patients presented at night and about 30% were under the influence of alcohol. CONCLUSIONS: Our study shows one of the largest cohort of patients suffering e-scooter accidents in Europe. Compulsory helmet use, stricter alcohol controls and locking periods could contribute significantly to safety.

Perivascular Space Burden and Cerebrospinal Fluid Biomarkers in US Veterans With Blast-Related Mild Traumatic Brain Injury.

Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. Dilated PVSs are putative markers of impaired cerebrospinal fluid (CSF) and interstitial fluid exchange, which plays an important role in removing cerebral waste. The aim of this cross-sectional, retrospective study was to define associations between biomarkers of inflammation and MRI-visible PVS (MV-PVS) burden in Veterans after blast-related mTBI (blast-mTBI) and controls. The CSF and plasma inflammatory biomarker concentrations were compared between blast-mTBI and control groups and correlated with MV-PVS volume and number per white matter cm3. Multiple regression analyses were performed with inflammatory biomarkers as predictors and MV-PVS burden as the outcome. Correction for multiple comparisons was performed using the Banjamini-Hochberg method with a false discovery rate of 0.05. There were no group-wise differences in MV-PVS burden between Veterans with blast-mTBI and controls. Greater MV-PVS burden was significantly associated with higher concentrations of several proinflammatory biomarkers from CSF (i.e., eotaxin, MCP-1, IL-6, IL-8) and plasma (i.e., MCP-4, IL-13) in the blast-mTBI group only. After controlling for sleep time and symptoms of post-traumatic stress disorder, temporal MV-PVS burden remained significantly associated with higher CSF markers of inflammation in the blast-mTBI group only. These data support an association between central, rather than peripheral, neuroinflammation and MV-PVS burden in Veterans with blast-mTBI independent of sleep. Future studies should continue to explore the role of blast-mTBI related central inflammation in MV-PVS development, as well as investigate the impact of subclinical exposures on MV-PVS burden.

Amnesia after Repeated Head Impact Is Caused by Impaired Synaptic Plasticity in the Memory Engram.

Subconcussive head impacts are associated with the development of acute and chronic cognitive deficits. We recently reported that high-frequency head impact (HFHI) causes chronic cognitive deficits in mice through synaptic changes. To better understand the mechanisms underlying HFHI-induced memory decline, we used TRAP2/Ai32 transgenic mice to enable visualization and manipulation of memory engrams. We labeled the fear memory engram in male and female mice exposed to an aversive experience and subjected them to sham or HFHI. Upon subsequent exposure to natural memory recall cues, sham, but not HFHI, mice successfully retrieved fearful memories. In sham mice the hippocampal engram neurons exhibited synaptic plasticity, evident in amplified AMPA:NMDA ratio, enhanced AMPA-weighted tau, and increased dendritic spine volume compared with nonengram neurons. In contrast, although HFHI mice retained a comparable number of hippocampal engram neurons, these neurons did not undergo synaptic plasticity. This lack of plasticity coincided with impaired activation of the engram network, leading to retrograde amnesia in HFHI mice. We validated that the memory deficits induced by HFHI stem from synaptic plasticity impairments by artificially activating the engram using optogenetics and found that stimulated memory recall was identical in both sham and HFHI mice. Our work shows that chronic cognitive impairment after HFHI is a result of deficiencies in synaptic plasticity instead of a loss in neuronal infrastructure, and we can reinstate a forgotten memory in the amnestic brain by stimulating the memory engram. Targeting synaptic plasticity may have therapeutic potential for treating memory impairments caused by repeated head impacts.

Role of regulatory non-coding RNAs in traumatic brain injury.

Traumatic brain injury (TBI) is a potentially fatal health event that cannot be predicted in advance. After TBI occurs, it can have enduring consequences within both familial and social spheres. Yet, despite extensive efforts to improve medical interventions and tailor healthcare services, TBI still remains a major contributor to global disability and mortality rates. The prompt and accurate diagnosis of TBI in clinical contexts, coupled with the implementation of effective therapeutic strategies, remains an arduous challenge. However, a deeper understanding of changes in gene expression and the underlying molecular regulatory processes may alleviate this pressing issue. In recent years, the study of regulatory non-coding RNAs (ncRNAs), a diverse class of RNA molecules with regulatory functions, has been a potential game changer in TBI research. Notably, the identification of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs has revealed their potential as novel diagnostic biomarkers and therapeutic targets for TBI, owing to their ability to regulate the expression of numerous genes. In this review, we seek to provide a comprehensive overview of the functions of regulatory ncRNAs in TBI. We also summarize regulatory ncRNAs used for treatment in animal models, as well as miRNAs, lncRNAs, and circRNAs that served as biomarkers for TBI diagnosis and prognosis. Finally, we discuss future challenges and prospects in diagnosing and treating TBI patients in the clinical settings.

Marcadores Neurales como Indicadores de Funciones Predictivas en Pacientes con Traumatismo Cerebral Moderado a Severo / Neural Markers as Indicators of Predictive Functions in Patients with Moderate to Severe Brain Trauma

Introducción. El traumatismo encéfalo craneano moderado a severo (TEC-MS) es una condición compleja que cambia la estructura y función del cerebro, afectando a personas de distintas edades. Los problemas cognitivos y motores son la mayor causa de discapacidad en individuos con TEC-MS crónico. Sin embargo, muchas de estas dificultades no son visibles de inmediato clasificándose como una "Epidemia silenciosa". Las principales alteraciones reportadas por los pacientes tienen relación con problemas de la memoria, atención y lentitud psicomotora, los cuales tienen un impacto en su independencia y funcionalidad. Objetivo. Este estudio tiene por objetivo discutir y revisar la evidencia disponible acerca de la capacidad de los pacientes crónicos con TEC-MS para generar predicciones en diferentes niveles de procesamiento cerebral. Métodos. Para esto, utilizamos desde las neurociencias el modelo teórico del código predictivo para explicar las respuestas neurofisiológicas adquiridas bajo un paradigma de predicción auditiva. Esta información es complementada con el reporte de datos preliminares de sujetos con TEC-MS y sujetos control, con el fin de ilustrar los aspectos teóricos discutidos. Conclusiones. Esto podría contribuir a una mejor comprensión de los mecanismos neurales detrás de los déficits cognitivos en esta población, aportando una perspectiva que nos oriente al desarrollo de nuestras estrategias terapéuticas.

Background. Moderate to severe traumatic brain injury (TBI-MS) is a complex condition that changes the structure and function of the brain, affecting people of different ages. Cognitive and motor problems are the major cause of disability in individuals with chronic ECT-MS. However, many of these difficulties are not immediately visible, classifying them as a "Silent Epidemic." The main alterations reported by patients are related to problems with memory, attention and psychomotor slowness, which have an impact on their independence and functionality. Objetive. This study aims to discuss and review the available evidence about the ability of chronic ECT-MS patients to generate predictions at different levels of brain processing. Methods. For this, we use the theoretical model of the predictive code from neuroscience to explain the neurophysiological responses acquired under an auditory prediction paradigm. This information is complemented with the report of preliminary data from subjects with ECT-MS and control subjects, in order to illustrate the theoretical aspects discussed. Conclusions. This could contribute to a better understanding of the neural mechanisms behind cognitive deficits in this population, providing a perspective that guides us in the development of our therapeutic strategies.

Effects of comprehensive nursing intervention on pressure ulcer after traumatic brain injury surgery: A meta-analysis.

Pressure ulcers (PUs) are a common complication in postoperative patients with traumatic brain injury, and this study used a meta-analysis to assess the effects of comprehensive nursing applied in PUs intervention in postoperative patients with traumatic brain injury. A computerised systematic search of the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (CBM), VIP and Wanfang databases was performed to collect publicly available articles on randomised controlled trials (RCTs) on the effects of comprehensive nursing interventions in postoperative patients with traumatic brain injury published up to August 2023. Two researchers independently completed the search and screening of the literature, extraction of data and quality assessment of the included literature based on the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Twenty-eight articles were finally included, for a cumulative count of 2641 patients, of which 1324 were in the intervention group and 1317 in the control group. The results of the meta-analysis showed that, compared with conventional nursing, comprehensive nursing intervention helped to reduce the incidence of PUs in postoperative patients with traumatic brain injury (5.14% vs. 19.67%, odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.16-0.29, p < 0.00001) and reduced the incidence of postoperative complications (7.87% vs. 25.84%, OR: 0.22, 95% CI: 0.11-0.43, p < 0.0001), while increasing patient satisfaction (96.67% vs. 75.33%, OR: 9.5, 95% CI: 3.63-24.88, p < 0.00001). This study concludes that a comprehensive nursing intervention applied to postoperative patients with traumatic brain injury can significantly reduce the incidence of PUs and postoperative complications as well as improve nursing satisfaction, and it is recommended for clinical promotion. However, due to the limitations of the studies' number and quality, more high-quality, large-sample RCTs are needed to further validate the conclusions of this study.

Delayed Diagnosis of Intracranial Trauma.

Introduction Trauma is one of the leading causes of death and hospitalization in the United States. Head trauma often results in significant morbidity and mortality. This study was undertaken to identify reasons for delay in diagnosis of intracranial trauma. Methods This retrospective study analyzed patients with intracranial trauma between 2016 and 2022, in which there was a delay of two days or more from the date of injury to the date of diagnosis. Results Among 809 patients with head trauma, 140 subjects were identified with delayed diagnosis of intracranial trauma (17.3%). The most common diagnoses were subdural hemorrhage (N = 82; 56%) and intraparenchymal hemorrhage (N = 33; 24%). The most common reasons for delay in diagnosis included patient delay in seeking care (N = 111; 79%), and delayed diagnosis during inpatient hospitalization (N = 16; 11%) (Chi-Square <0.0001) (Table 2). Among inpatients with delayed diagnosis, confounding issues included alcohol intoxication (N = 4; 3%), other injuries (N = 9; 6%), and mental health issues (N = 2; 1%). Conclusions Among patients with delayed diagnosis of intracranial trauma, the majority of delays in diagnosis were due to patient delay in seeking care. Future directions may include improved public education regarding trauma and the importance of seeking timely medical care.

Access to Rehabilitation After Hospitalization for Traumatic Brain Injury: A National Longitudinal Cohort Study in Sweden.

BACKGROUND: Rehabilitation is suggested to improve outcomes following traumatic brain injury (TBI), however, the extent of access to rehabilitation among TBI patients remains unclear. OBJECTIVE: To examine the level of access to rehabilitation after TBI, and its association with health and sociodemographic factors. METHOD: We conducted a longitudinal cohort study using Swedish nationwide healthcare and sociodemographic registers. We identified 15 880 TBI patients ≥18 years hospitalized ≥3 days from 2008 to 2012 who were stratified into 3 severity groups; grade I (n = 1366; most severe), grade II (n = 5228), and grade III (n = 9268; least severe). We examined registered contacts with specialized rehabilitation or geriatric care (for patients ≥65 years) during the hospital stay, and/or within 1 year post-discharge. We performed a generalized linear model analysis to estimate the risk ratio (RR) for receiving specialized rehabilitation or geriatric care after a TBI based on sociodemographic and health factors. RESULTS: Among TBI patients, 46/35% (grade I), 14/40% (grade II), and 5/18% (grade III) received specialized rehabilitation or geriatric care, respectively. Being currently employed or studying was positively associated (RR 1.7, 2.3), while living outside of a city area was negatively associated (RR 0.36, 0.79) with receiving specialized rehabilitation or geriatric care. Older age and a prior substance use disorder were negatively associated with receiving specialized rehabilitation (RR 0.51 and 0.81). CONCLUSION: Our results suggest insufficient and unequal access to rehabilitation for TBI patients, highlighting the importance of organizing and standardizing post-TBI rehabilitation to meet the needs of patients, regardless of their age, socioeconomic status, or living area.

Chronic traumatic encephalopathy-neuropathologic change in a routine neuropathology service: 7-year follow-up.

To follow our 2016 study of chronic traumatic encephalopathy neuropathologic change (CTE-NC) in our forensic autopsy service, we prospectively screened all cases with clinical histories of multiple concussions, persistent post-head injury symptoms, or ≥3 hospital investigations for head injuries from 2016 to 2022 inclusive using hyperphosphorylated tau (p-tau) immunostaining. The cases had routine brain sampling plus 4-6 additional lateral hemisphere samples. When "pathognomonic" CTE-NC lesions were identified, additional p-tau immunostaining was done for CTE-NC staging. Of ∼1100 adult brains aged 18-65 years examined, 85 were screened, and 16 were positive for CTE-NC (2 women, 14 men, ages 35-61 years, median 47 years). Alcohol abuse was documented in 14 of 16 (8 in combination with other substances); 5 had developmental brain anomalies (2 presumed genetic, 3 from acquired perinatal insults). Widespread p-tau deposits (high CTE-NC) were found in 7 of 16. Old brain contusions were present in 9 of 16, but CTE-NC did not colocalize. Of particular interest were (1) a man with FGFR3 mutation/hypochondroplasia and life-long head banging, (2) a woman with cerebral palsy and life-long head banging, and (3) a man with bilateral peri-Sylvian polymicrogyria, alcohol abuse, and multiple head injuries. Thus, CTE-NC occurs in association with repeated head trauma outside contact sports. Substance abuse is a common determinant of risk behavior. The utility of diagnosing mild-/low-stage CTE-NC in this population remains to be determined.

Role of brain metabolites during acute phase of mild traumatic brain injury in prognosis of post-concussion syndrome: A 1H-MRS study.

This study has investigated the potency and accuracy of early magnetic resonance spectroscopy (MRS) to predict post-concussion syndrome (PCS) in adult patients with a single mild traumatic brain injury (mTBI) without abnormality on a routine brain scan. A total of 48 eligible mTBI patients and 24 volunteers in the control group participated in this project. Brain MRS over regions of interest (ROI) and signal stop task (SST) were done within the first 72 hours of TBI onset. After six months, PCS appearance and severity were determined. In non-PCS patients, N-acetyl aspartate (NAA) levels significantly increased in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) relative to the control group, however, this increase of NAA levels were recorded in all ROI versus PCS subjects. There were dramatic declines in creatinine (Cr) levels of all ROI and a decrease in choline levels of corpus callosum (CC) in the PCS group versus control and non-PCS ones. NAA and NAA/Cho values in ACC were the main predictors of PCS appearance. The Cho/Cr level in ACC was the first predictor of PCS severity. Predicting accuracy was higher in ACC than in other regions. This study suggested the significance of neuro-markers in ACC for optimal prediction of PCS and rendered a new insight into the biological mechanism of mTBI that underpins PCS.

Fluid Resuscitation in Patients With Traumatic Brain Injury: A Comprehensive Review.

Patients with traumatic brain injury (TBI) or head trauma present challenges for emergency physicians and neurosurgeons. Traumatic brain injury is currently a community health issue. For the best possible care, it is crucial to understand the various helpful therapy techniques in the pre-operative and pre-hospital phases. The initial rapid infusion of large volumes of mannitol and a hypertonic crystalloid solution to restore blood pressure and blood volume is the current standard of care for people with combined hemorrhagic shock (HS) and traumatic brain injury. The selection and administration of fluids to trauma and traumatic brain injury patients may be especially helpful in preventing subsequent ischemic brain damage because of the hemodynamic stabilizing effects of these fluids in hypovolemic shock. Traumatic brain injury is an essential factor that may lead to disability and death in a patient. Traumatic brain damage can develop either as a direct result of the trauma or as a result of the initial harm. Significant neurologic problems, such as cranial nerve damage, dementia, seizures, and Alzheimer's disease, can develop after a traumatic brain injury. The comorbidity of the victims may also be significantly increased by additional psychiatric problems such as psychological diseases and other behavioral and cognitive sequels. We review the history of modern fluid therapy, complications after traumatic brain injury, and the use of fluid treatment for decompressive craniectomy and traumatic brain injury.