Polydatin ameliorates early brain injury after subarachnoid hemorrhage through up-regulating SIRT1 to suppress endoplasmic reticulum stress.

Objective: This study aims to investigate the inhibitory effect of Polydatin (PD) on endoplasmic reticulum (ER) stress following subarachnoid hemorrhage (SAH) and to elucidate the underlying mechanisms. Methods: A standard intravascular puncture model was established to mimic SAH in mice. Neurological functions were assessed using neurological scoring, Grip test, and Morris water maze. Brain edema and Evans blue extravasation were measured to evaluate blood-brain barrier permeability. Western blot and quantitative real-time polymerase chain reaction (PCR) analyses were performed to examine protein and mRNA expressions related to ER stress. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to detect cell apoptosis, and transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum. Results: The results indicated that PD significantly reduced brain edema and Evans blue extravasation after SAH, improving neurological function. Compared to the SAH group, the expression levels of ER stress-related proteins including glucose-regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were significantly lower in the PD-treated group. Moreover, PD significantly enhances the protein expression of Sirtuin 1 (SIRT1). Validation with sh-SIRT1 confirmed the critical role of SIRT1 in ER stress, with PD's inhibitory effect on ER stress being dependent on SIRT1 expression. Additionally, PD attenuated ER stress-mediated neuronal apoptosis and SAH-induced ferroptosis through upregulation of SIRT1. Conclusion: PD alleviates ER stress following SAH by upregulating SIRT1 expression, thereby mitigating early brain injury. The protective effects of PD are mediated through SIRT1, which inhibits ER stress and reduces neuronal apoptosis and ferroptosis.

Development and validation of a clinical nomogram for predicting in-hospital mortality in patients with traumatic brain injury prehospital: A retrospective study.

Objective: Traumatic brain injury (TBI) is among the leading causes of death and disability globally. Identifying and assessing the risk of in-hospital mortality in traumatic brain injury patients at an early stage is challenging. This study aimed to develop a model for predicting in-hospital mortality in TBI patients using prehospital data from China. Methods: We retrospectively included traumatic brain injury patients who sustained injuries due to external forces and were treated by pre-hospital emergency medical services (EMS) at a tertiary hospital. Data from the pre-hospital emergency database were analyzed, including demographics, trauma mechanisms, comorbidities, vital signs, clinical symptoms, and trauma scores. Eligible patients were randomly divided into a training set (241 cases) and a validation set (104 cases) at a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were employed to identify independent risk factors. Analyzed the discrimination, calibration, and net benefit of the nomogram across both groups. Results: 17.40 % (42/241) of TBI patients died in the hospital in the training set, while 18.30 % (19/104) in the validation set. After analysis, chest trauma (odds ratio [OR] = 4.556, 95 % confidence interval [CI] = 1.861-11.152, P = 0.001), vomiting (OR = 2.944, 95%CI = 1.194-7.258, P = 0.019), systolic blood pressure (OR = 0.939, 95%CI = 0.913-0.966, P < 0.001), SpO2 (OR = 0.778, 95%CI = 0.688-0.881, P < 0.001), and heart rate (OR = 1.046, 95%CI = 1.015-1.078, P = 0.003) were identified as independent risk factors for in-hospital mortality in TBI patients. The nomogram based on the five factors demonstrated well-predictive power, with an area under the curve (AUC) of 0.881 in the training set and 0.866 in the validation set. The calibration curve and decision curve analysis showed that the predictive model exhibited good consistency and covered a wide range of threshold probabilities in both sets. Conclusion: The nomogram based on prehospital data demonstrated well-predictive performance for in-hospital mortality in TBI patients, helping prehospital emergency physicians identify and assess severe TBI patients earlier, thereby improving the efficiency of prehospital emergency care.

Associations between concussion and more severe TBIs, mild cognitive impairment, and early-onset dementia among military retirees over 40 years.

Background and objectives: As the population of U.S. service members (SMs) who have sustained concussions and more severe traumatic brain injuries (TBIs) during military service ages, understanding the long-term outcomes associated with such injuries will provide critical information that may promote long-term assessment, support, and rehabilitation following military service. The objective of this research was to examine whether concussion and more severe TBIs are associated with greater risk of precursors to dementia (i.e., mild cognitive impairment, memory loss), early-onset dementia, and any dementia. Methods: This study used a retrospective cohort design wherein archival medical and career records from 1980 to 2020 identified U.S. military personnel who retired from military service and their corresponding Tricare-reimbursable medical encounters in inpatient and/or outpatient settings in military treatment facilities and/or purchased care settings both before and after retirement. All military personnel who served on active duty between 1980 and 2020 and were at least 45 years of age by 2020 were eligible for inclusion (N = 6,092,432). Those who were discharged from military service with a retirement designation, and were thus eligible for Tricare for Life, were included in the analytic sample (N = 1,211,972). Diagnoses of concussion and more severe TBI during active duty service recorded in inpatient settings between 1980 and 2020 and in outpatient settings from 2001 to 2020 were identified. Focal outcomes of interest included memory loss, mild cognitive impairment, Alzheimer's, Lewy Body dementia, frontotemporal dementia, and vascular dementia. Dementia diagnoses before age 65 were labeled early-onset. Results: Those with (vs. without) concussion diagnoses during military service were significantly more likely to be diagnosed with memory loss and mild cognitive impairment and any of the dementias examined. However, they were not at greater risk of being diagnosed with early-onset dementia. Discussion: Military SMs diagnosed with concussion may be at elevated risk for long-term neurodegenerative outcomes including memory loss, mild cognitive impairment, and dementia. As the population of SMs who sustained TBI during the Global War on Terror continue to age, the prevalence of dementia will increase and may bring a unique burden to the VHA.

Validation of optimised intracranial spectroscopic probe for instantaneous in-situ monitoring and classification of traumatic brain injury.

The development of an optical interface to directly distinguish the brain tissue's biochemistry is the next step in understanding traumatic brain injury (TBI) pathophysiology and the best and most appropriate treatment in cases where in-hospital intracranial access is required. Despite TBI being a globally leading cause of morbidity and mortality in patients under 40, there is still a lack of objective diagnostical tools. Further, given its pathophysiological complexity the majority of treatments provided are purely symptomatic without standardized therapeutic targets. Our tailor-engineered prototype of the intracranial Raman spectroscopy probe (Intra-RSP) is designed to bridge the gap and provide real-time spectroscopic insights to monitor TBI and its evolution as well as identify patient-specific molecular targets for timely intervention. Raman spectroscopy being rapid, label-free and non-destructive, renders it an ideal portable diagnostics tool. In combination with our in-house developed software, using machine learning algorithms for multivariate analysis, the Intra-RSP is shown to accurately differentiate simulated TBI conditions in rat brains from the healthy controls, directly from the brain surface as well as through the rat's skull. Using clinically pre-established methods of cranial entry, the Intra-RSP can be inserted into a 2-piece optimised cranial bolt with integrated focussing and correctly identify a sample in real-life conditions with an accuracy >80 %. To further validate the Intra-RSP's efficiency as a TBI monitoring device, rat brains mildly damaged from inflicted spinal cord injury were found to be correctly classified with 94.5 % accuracy. Through optimization and rigorous in-vivo validation, the Intra-RSP prototype is envisioned to seamlessly integrate into existing standards of neurological care, serving as a minimally invasive, in-situ neuromonitoring tool. This transformative approach has the potential to revolutionize the landscape of neurological care by providing clinicians with unprecedented insights into the nature of brain injuries and fostering targeted, timely and effective therapeutic interventions.

Liver protects neuron viability and electrocortical activity in post-cardiac arrest brain injury.

Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

Glucocorticoid receptor response and glucocorticoid-induced leucine zipper expression in neutrophils of critically ill patients with traumatic and non-traumatic brain injury.

Objective: Critically ill patients, including those with brain injuries (BI), are frequently hospitalized in an intensive care unit (ICU). As with other critical states, an adequate stress response is essential for survival. Research on the hypothalamic-pituitary-adrenal gland (HPA) axis function in BI has primarily focused on assessing ACTH and cortisol levels. However, the immunological, metabolic, and hemodynamic effects of glucocorticoids (GCs) are mediated through the glucocorticoid receptor (GCR), a ubiquitously distributed intracellular receptor protein. Data on GCR-α expression and its signaling in acute BI injury are lacking. Methods: We designed a prospective observational study, carried out in one academic multi-disciplinary ICU. Forty-two critically ill patients with acute (BI)were included. These patients suffered from traumatic BI (N= 20), subarachnoid hemorrhage (N= 12), intracranial hemorrhage (N= 7), or ischemic stroke (N= 3). All patients were steroid-free. Twenty-four age and sex-matched healthy controls were used for comparison. Results: Expression of GCR-α and the glucocorticoid-inducible leucine zipper (GILZ), serum cortisol, interleukins (IL) 6, 8, 10 and TNF- α, and the BI biomarkers glial fibrillary acidic protein (GFAP) and total Tau were measured on ICU admission (within 48 hours) and 5-7 days from admission. Compared to healthy controls, in the critically ill patients with BI, GCR-α mRNA expression was significantly downregulated on admission, and after 5-7 days in the ICU (2.3-fold, p<0.05 and 2.6-fold, p<0.01, respectively). Even though GCR-α was downregulated, its downstream gene, GILZ, was expressed at the same levels as in normal controls on admission and was significantly upregulated 5-7 days following admission (2-fold, p<0.001). TNF-α levels were undetectable at both time-points. GCR-α expression levels inversely correlated with IL-6. The levels of cortisol and the BI biomarkers did not differ between the 2 time-points. Conclusions: We provide novel evidence on the downregulated expression and upregulated signaling of the ligand-binding and functionally active GCR-α isoform in the polymorphonuclear neutrophils (PMNs) of critically ill patients with BI. The increased GILZ expression indicates an increased GC sensitivity in the PMNs of BI critically ill patients.

Plasma biomarkers in chronic single moderate-severe traumatic brain injury.

Blood biomarkers are an emerging diagnostic and prognostic tool that reflect a range of neuropathological processes following traumatic brain injury (TBI). Their effectiveness in identifying long-term neuropathological processes after TBI is unclear. Studying biomarkers in the chronic phase is vital because elevated levels in TBI might result from distinct neuropathological mechanisms during acute and chronic phases. Here, we examine plasma biomarkers in the chronic period following TBI and their association with amyloid and tau PET, white matter microarchitecture, brain age and cognition. We recruited participants ≥40 years of age who had suffered a single moderate-severe TBI ≥10 years previously between January 2018 and March 2021. We measured plasma biomarkers using single molecule array technology [ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light (NfL), tau, glial fibrillary acidic protein (GFAP) and phosphorylated tau (P-tau181)]; PET tracers to measure amyloid-ß (18F-NAV4694) and tau neurofibrillary tangles (18F-MK6240); MRI to assess white matter microstructure and brain age; and the Rey Auditory Verbal Learning Test to measure verbal-episodic memory. A total of 90 post-TBI participants (73% male; mean = 58.2 years) were recruited on average 22 years (range = 10-33 years) post-injury, and 32 non-TBI control participants (66% male; mean = 57.9 years) were recruited. Plasma UCH-L1 levels were 67% higher {exp(b) = 1.67, P = 0.018, adjusted P = 0.044, 95% confidence interval (CI) [10% to 155%], area under the curve = 0.616} and P-tau181 were 27% higher {exp(b) = 1.24, P = 0.011, adjusted P = 0.044, 95% CI [5% to 46%], area under the curve = 0.632} in TBI participants compared with controls. Amyloid and tau PET were not elevated in TBI participants. Higher concentrations of plasma P-tau181, UCH-L1, GFAP and NfL were significantly associated with worse white matter microstructure but not brain age in TBI participants. For TBI participants, poorer verbal-episodic memory was associated with higher concentration of P-tau181 {short delay: b = -2.17, SE = 1.06, P = 0.043, 95% CI [-4.28, -0.07]; long delay: bP-tau = -2.56, SE = 1.08, P = 0.020, 95% CI [-4.71, -0.41]}, tau {immediate memory: bTau = -6.22, SE = 2.47, P = 0.014, 95% CI [-11.14, -1.30]} and UCH-L1 {immediate memory: bUCH-L1 = -2.14, SE = 1.07, P = 0.048, 95% CI [-4.26, -0.01]}, but was not associated with functional outcome. Elevated plasma markers related to neuronal damage and accumulation of phosphorylated tau suggest the presence of ongoing neuropathology in the chronic phase following a single moderate-severe TBI. Plasma biomarkers were associated with measures of microstructural brain disruption on MRI and disordered cognition, further highlighting their utility as potential objective tools to monitor evolving neuropathology post-TBI.

Contusion expansion, low platelet count and bifrontal contusions are associated with worse patient outcome following traumatic brain injury-a retrospective single-center study.

BACKGROUND: Cortical contusions are common in moderate-severe traumatic brain injury (TBI). Cortical contusions often expand, potentially causing neuro-worsening several hours to days post-trauma. While contusion expansion (CE) may affect outcome, potential clinical and radiological markers that can predict CE have been insufficiently explored. In the present single-center retrospective observational cohort study, we evaluated clinical outcome by the Glasgow Outcome Scale extended (GOSE) scale and evaluated risk factor for CE. METHOD: Adult TBI patients > 18 years of age, and of all injury severities, were included. Main variables of interest were low platelet count, defined as < 150 × 109/L, presence of bifrontal contusions and CE, defined as absolute contusion volume increase in cm3. Factors associated with CE and clinical outcome according to GOSE were analyzed. RESULTS: Between 2012-2022, 272 patients were included. Contusion size on admission correlated positively with CE, as did the Marshall and Rotterdam radiological classification scores. Bifrontal contusions were significantly larger at admission, experienced larger CE, and had a worse outcome than contusions in other locations. Patients with a platelet count < 150 × 109/L experienced a greater volume CE and had a worse outcome when compared to patients with a normal platelet count. In a multivariate analysis, CE remained significantly associated with a poor outcome six months post- injury. CONCLUSION: Contusion volume at admission, Marshall CT classification and Rotterdam CT score, positively correlated to CE. Bifrontal contusions and a platelet count < 150 × 109/L were associated with CE, and a poor clinical outcome. Large CE volumes were associated with a worse clinical outcome, and CE was per se associated with outcome in a multivariate analysis. Management of these risk factors for CE in the acute post-injury setting may be needed to attenuate contusion expansion and to improve clinical outcome in TBI patients suffering from cortical contusion injuries.

Neuronal Death: Now You See It, Now You Don't.

Fatally injured neurons may necrose and rupture immediately, or they may initiate a programmed cell death pathway and then wait for microglial phagocytosis. Biochemical and histopathologic assays of neuronal death assess the numbers of neurons awaiting phagocytosis at a particular time point after injury. This number varies with the fraction of neurons that have necrosed vs initiated programmed cell death, the time elapsed since injury, the rate of phagocytosis, and the assay's ability to detect neurons at different stages of programmed cell death. Many of these variables can be altered by putatively neurotoxic and neuroprotective interventions independent of the effects on neuronal death. This complicates analyses of neurotoxicity and neuroprotection and has likely contributed to difficulties with clinical translation of neuroprotective strategies after brain injury. Time-resolved assays of neuronal health, such as ongoing expression of transgenic fluorescent proteins, are a useful means of avoiding these problems.

Temporary ambiguity and memory for the context of spoken language in adults with moderate-severe traumatic brain injury.

Language is processed incrementally, with addressees considering multiple candidate interpretations as speech unfolds, supporting the retention of these candidate interpretations in memory. For example, after interpreting the utterance, "Click on the striped bag", listeners exhibit better memory for non-mentioned items in the context that were temporarily consistent with what was said (e.g., dotted bag), vs. not consistent (e.g., dotted tie), reflecting the encoding of linguistic context in memory. Here, we examine the impact of moderate-severe traumatic brain injury (TBI) on memory for the contexts of language use. Participants with moderate-severe TBI (N=71) and non-injured comparison participants (NC, N=85) interpreted temporarily ambiguous utterances in rich contexts. A subsequent memory test demonstrated that participants with TBI exhibited impaired memory for context items and an attenuated memory advantage for mentioned items compared to NC participants. Nonetheless, participants with TBI showed similar, although attenuated, patterns in memory for temporarily-activated items as NC participants.

Attrition, adherence, and compliance to exercise training interventions in persons with traumatic brain injury: a systematic review of training studies.

BACKGROUND: Exercise training (ET) is a promising rehabilitation approach for long-term negative consequences of traumatic brain injury (TBI). However, little is known regarding overall rates of attrition, adherence, and compliance to ET in TBI. OBJECTIVE: The purpose of this systematic review was to estimate average attrition, adherence, and compliance rates in ET studies in persons with TBI. METHODS: Databases were searched from inception to April 15, 2024. Two authors independently extracted data related to attrition, adherence, compliance, and possible moderators identified a priori. RESULTS: The average rate of attrition from 45 studies was 14.4%, although the majority of studies had small sample sizes (i.e. n < 42). Based on hierarchical linear regression, the most influential predictors of attrition were sample size and study design. A minority of studies reported adherence (44.4%) or compliance (22.2%) but those that did reported good average adherence (85.1%) and compliance (77.7%). These studies support the ability of persons with TBI to complete an ET intervention as prescribed. CONCLUSIONS: Researchers can use this information to ensure adequate power to detect a true effect of ET in persons with TBI. Researchers conducting ET studies in persons with TBI should clearly and thoroughly report data on attrition, adherence, and compliance.

Bioinformatics analysis of the mechanisms of traumatic brain injury-associated dementia based on the competing endogenous RNA.

RATIONALE: Traumatic brain injury (TBI) is a critical condition associated with cognitive impairments, including dementia. This study is aimed to construct a long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network based on bioinformatics analysis and explore molecular mechanisms underlying post-TBI dementia. METHODS: GSE104687 and GSE205661 datasets were downloaded from Gene Expression Omnibus database. Molecular Signatures Database (MSigDB) was used to search oxidative stress-, metabolism- and immune-related genes as the target gene datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were carried out for functional annotation and enrichment analysis. A TBI mouse model was built to validate the expression of NF2, PLXNA2, NCBP2 and U2SURP in brain tissues. RESULTS: A total of 7 differentially expressed lncRNAs (DElncRNAs) and 191 DEmRNAs were obtained. Subsequent to differential expression (DE) analysis, a lncRNA-miRNA-mRNA network was established. Notably, 13 key DEmRNAs were identified, potentially playing pivotal roles in the pathogenesis of TBI-induced dementia. By comparing the target gene datasets with 13 DEmRNAs, we identified 4 target genes that overlap with the 13 DEGmRNAs, namely NF2, PLXNA2, NCBP2 and U2SURP. Functional enrichment analysis highlighted the involvement of neuronal projections in the dementia-enriched cluster, while the protective cluster showed associations with protein synthesis and ubiquitination pathways. Importantly, we explored potential drug interventions based on interactions with the above 4 target genes. Additionally, drug interaction prediction showed that NF2 could interact with SELUMETINIB, EVEROLIMUS and TEMSIROLIMUS. CONCLUSION: Our study provides insights into the complex regulatory networks underlying post-TBI dementia and suggests a potential role for three classes of drugs in managing dementia symptoms in TBI-induced dementia.

Comment on, "Hypoxia preconditioning protects neuronal cells against traumatic brain injury through stimulation of glucose transport mediated by HIF-1α/GLUTs signaling pathway in rat".

Wu et al. (2021) investigated the neuroprotective effects of hypoxia preconditioning (HPC) in a rat model of traumatic brain injury (TBI). The study demonstrated that HPC enhances brain resilience to TBI by upregulating glucose transporters GLUT1 and GLUT3 through the HIF-1α signaling pathway. Comprehensive molecular and histological analyses confirmed increased expression of these transporters, correlating with reduced neuronal apoptosis and cerebral edema. The robust methodology, including rigorous statistical validation and time-course assessments, underscores HPC's potential therapeutic role in mitigating neuronal loss and improving glucose transport post-injury. However, the study could be strengthened by incorporating additional preconditioning controls, comparative analyses with other neuroprotective strategies, and exploring downstream metabolic effects in greater detail. Furthermore, expanding the research to include diverse animal models and examining sex-dependent responses would enhance the generalizability and translational relevance of the findings. Future studies should also integrate metabolic flux analysis and advanced imaging techniques to further elucidate HPC's mechanisms of action.

Disinhibition, rather than moderate-to-severe traumatic brain injury, moderates the impact of anger provocation on subjective emotional experience.

OBJECTIVE: Altered reactivity to emotional stimuli is common after traumatic brain injury (TBI), which is suggested to reflect difficulties with emotion regulation. While disinhibition is common after moderate-to-severe TBI, limited research has investigated the link between disinhibition and emotional reactivity in this clinical group. The aim of this research, therefore, was to investigate the relationship between disinhibition and TBI to anger provocation. METHOD: Thirty-five individuals with moderate-to-severe TBI and thirty-one controls completed an anger induction task. Participants rated their experience of emotions and subjective arousal before and after the induction. Heart rate, respiration and skin conductance were also measured. Disinhibition was measured using the Frontal Systems Behavior Scale. RESULTS: In the full sample, the mood induction led to increased skin conductance, respiration, and self-reported anger, tension, arousal and negative mood. There were no differences between those with TBI and controls. Disinhibition interacted with the impact of anger provocation on subjective, but not objective, outcomes such that those elevated in disinhibition reported increased feelings of anger and tension in response to the mood induction. Disinhibition did not interact with TBI across any subjective and objective emotional measures examined in response to mood induction. CONCLUSIONS: While anger causes emotional changes for all individuals, these changes are particularly pronounced among those who are disinhibited, irrespective of whether an individual has sustained a TBI. This is an important consideration when examining emotional regulation post-TBI as the degree of disinhibition appears to alter subjective interpretations of emotional events, which could lead to emotion dysregulation.

Influence of pre-existing conditions and concussion history on post-concussion symptom severity and recovery time in collegiate athletes.

Mental health conditions and concussion history reported by a collegiate athlete may contribute to prolonged recovery and symptom severity after concussion. This work examined the potential associations among concussion history, pre-existing conditions, and sex relative to initial symptom severity and recovery duration following sport-related concussion (SRC) in a cohort of Division 1 NCAA athletes. This prospective cohort study analyzed symptom severity, recovery and return-to-play times reported post-SRC using data collected as part of the Pac-12 CARE Affiliated Program and Health Analytics Program. Health history questionnaires which included self-reported history of pre-existing conditions were completed at baseline. When consented athletes were diagnosed with a concussion, daily post-concussion symptom scores were evaluated until an athlete was clinically determined to be asymptomatic. Generalized linear and Cox proportional hazards models were used to determine associations between pre-existing conditions and recovery and return-to-play times. 92 concussions met inclusion criteria. Notable differences in initial symptom severity existed between females and males who had mood disorders ([Cohen's d] = 0.51) and ADHD (d = 0.93). The number of previous concussions was a strong predictor of athletes reporting pre-existing mood disorders, depression, anxiety, and ADHD (p = 0.008-0.04). Females with ≥2 previous concussions required more days to return-to-play than males (d = 0.31-0.72). Weekly recovery and return-to-play probabilities substantially differed between athletes that did or did not have learning disorders (HRRecovery = 0.32, HRRTP = 0.22, d = 1.96-2.30) and ADHD (HRRecovery = 3.38, HRRTP = 2.74, d = 1.71-4.14). Although no association existed between concussion history and acute symptom severity, collegiate athletes with a history of concussion had higher probabilities of reporting depression, mood disorders, anxiety, and ADHD. Having ADHD or learning disorders likely strongly affects time to recovery and return-to-play for collegiate athletes.

Controlled lumbar cerebrospinal fluid drainage effectively decreases the need for second and third tier interventions for intracranial hypertension in severe traumatic brain injury patients.

INTRODUCTION: Early treatment of elevated intracranial pressure (ICP) is a cornerstone of the therapy in severe traumatic brain injury (TBI) patients. Treatment of refractory high ICP however, remain challenging as only limited and risky third-tier therapeutic interventions are available. Controlled lumbar cerebrospinal fluid (CSF) drainage has been known as an efficient method of ICP reduction after TBI for decades, but it is not recommended in international guidelines because of low evidence background and safety issues. Our centre has a long-standing experience using this intervention for more than 15 years. Here we present our data about the safety and efficacy of controlled lumbar drainage to avoid further second- and third tier ICP lowering therapies and beneficially influence functional outcome. METHODS: Observational (retrospective and prospective) analysis was performed using demographic, clinical and outcome data of severe TBI patients admitted to our centre. Analysis was retrospective between 2008 and 2013 and prospective from 2014 to 2019. Only severe TBI patients (GCS<9) with ICP monitoring were enrolled. Lumbar drainage (LD) was used as a second-tier therapy to control intracranial hypertension in salvageable patients with normal haemostasis and discernible basal cisterns on pre-interventional CT scan. RESULTS: Data of 45 patients were analysed. Patients were young, comatose and with severe injuries (median age: 29, GMS: 4, ISS: 25). Lumbar drain was inserted mainly on the first week and maintained for further 5 days. Episodes of intracranial hypertension (ICP>20 Hgmm) within one day (10 vs 2) were reduced. The need of additional second- and third-line therapies (deep sedation, hyperventilation, barbiturate administration, decompressive craniectomy) also significantly decreased (60 vs 25 interventions, p<0.001). The in-hospital mortality and 6-month functional outcome were more favourable than the whole TBI population and as predicted by prognostic calculations (mortality: 16% vs. 48 %; GOSE 1-4: 49% vs. 65% vs CRASH: 87% vs. IMPACT: 51 %) in this period. CONCLUSIONS: Our results support the view that controlled lumbar drainage is a highly efficient method to manage intracranial hypertension and significantly decreases the need of further harmful ICP lowering therapies without altering functional outcome of severe TBI patients.

Acupuncture Treatment for Chronic Post-traumatic Headache in Individuals with Mild Traumatic Brain Injury: A Pilot Study.

Chronic post-traumatic headache (CPTH) after a mild traumatic brain injury (mTBI) has been reported in up to 60% of patients and can be extremely debilitating. While pharmacological treatments are typically used for CPTH, they frequently cause side effects and have limited effectiveness, leading individuals with CPTH to be unsatisfied with current treatment options and to seek non-pharmacological options. Acupuncture has been identified as a potential treatment option; however, the evidence in this population remains limited. The overall goal of this study was to examine the effect of a once weekly (e.g., low dose) vs. twice weekly (e.g., high dose) of acupuncture treatment on CPTH in individuals with mTBI. Thirty-eight individuals were randomized to receive either 5 or 10 acupuncture treatments using a standard protocol over 5 weeks. The protocol consisted of 14 points using traditional acupuncture and 4 points using electroacupuncture. Headache outcomes, safety, treatment adherence, sleep quality, and quality of life (QOL) were assessed. The results showed that while there were no differences between dose groups for any of the outcomes assessed, acupuncture significantly reduced the number of headache days and headache pain intensity in individuals with CPTH. There were no significant changes in acute medication use or sleep quality. While there were some QOL improvements identified, these results should be interpreted with caution. Overall, acupuncture was shown to be safe and well-tolerated in people with CPTH after mTBI, and 5 acupuncture treatments using a standardized protocol shows promise in providing headache relief for this population.

A mouse model of temporal lobe contusion.

Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, "computed tomography (CT)-positive", i.e., hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. tlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days, and non-convulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.