Sex-dependent perturbations in risky choice behavior and prefrontal tyrosine hydroxylase levels induced by repetitive mild traumatic brain injury.

Head trauma often impairs cognitive processes mediated within the prefrontal cortex (PFC), leading to impaired decision making and risk-taking behavior. Mild traumatic brain injury (mTBI) accounts for approximately 80 % of reported head injury cases. Most neurological symptoms of a single mTBI are transient; however, growing evidence suggests that repeated mTBI (rmTBI) results in more severe impairments that worsen with each subsequent injury. Although mTBI-induced disruption of risk/reward decision making has been characterized, the potential for rmTBI to exacerbate these effects and the neural mechanisms involved are unknown. Catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), modulate PFC-mediated functions. Imbalances in catecholamine function have been associated with TBI and may underlie aberrant decision making. We used a closed head-controlled cortical impact (CH-CCI) model in rats to evaluate the effects of rmTBI on performance of a probabilistic discounting task of risk/reward decision making behavior and expression levels of catecholamine regulatory proteins within the PFC. RmTBI produced transient increases in risky choice preference in both male and female rats, with these effects persisting longer in females. Additionally, rmTBI increased expression of the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), within the orbitofrontal (OFC) region of the PFC in females only. These results suggest females are more susceptible to rmTBI-induced disruption of risk/reward decision making behavior and dysregulation of catecholamine synthesis within the OFC. Together, using the CH-CCI model of rodent rmTBI to evaluate the effects of multiple insults on risk-taking behavior and PFC catecholamine regulation begins to differentiate how mTBI occurrences affect neuropathological outcomes across different sexes.

Concussion management and concussion recovery in Gaelic games: a qualitative analysis.

Background: The purpose of this qualitative research study was to interview current and retired Gaelic games athletes to understand the current landscape of concussion recovery in Gaelic sports from the athlete perspective. Methods: A grounded theory methodology was employed to explore the experiences of a cohort of Gaelic games athletes (n = 22) regarding recovery from concussion, the levels of concussion awareness in Gaelic sports and their opinions on current concussion identification protocols. The study's data were gathered through semi-structured interviews. Results: Two major themes were identified, (1) Male and female athletes experience a range of acute and chronic symptoms post-SRC and (2) Gaelic sports athletes are expected to demonstrate constant allegiance and commitment to the GAA. These themes were further divided into categories and subcategories. Conclusion: Based on the experiences of the cohort of Gaelic sports athletes, there exists a wide variation of SRC symptomology in the acute, and chronic (post-concussion syndrome) phases. In many cases, there are reports of long-term side effects associated with the perceived mismanagement or misdiagnosis of SRC in Gaelic sports. Gaelic sports athletes require a more robust SRC management system to support and manage SRC in the acute, chronic and long-term phases.

Pcv-aCO2/Ca-cvO2 Combined with Optic Nerve Sheath Diameter in Predicting Elevated Intracranial Pressure of Patients with Traumatic Brain Injury in Prehospital Setting.

Purpose: To investigate a correlation between the central venous minus arterial CO2 pressure to arterial minus central venous O2 content ratio (Pcv-aCO2/Ca-cvO2) combined with optic nerve sheath diameter (ONSD) in predicting prehospital elevated intracranial pressure (ICP) in traumatic brain injury (TBI) patients. Patients and Methods: This was a prospective observational study of all adult TBI patients from the surgical intensive care unit who underwent invasive ICP monitoring between January 2023 and December 2023. Using a Delica MVU-6300 machine with 14-5 MHz linear probe to measure ONSD. We drew blood samples for arterial and central venous blood gases to measure and calculate the following indicators such as Pcv-aCO2, Ca-cvO2, and Pcv-aCO2/Ca-cvO2 ratio. ONSD and Pcv-aCO2/Ca-cvO2 were recorded during the first 3 days after admission. Simultaneous ICP values were gained from the invasive monitoring. Associations between ONSD, Pcv-aCO2/Ca-cvO2 and simultaneous ICP were explored by Spearman correlation analysis. We constructed an ROC curve to identify the ONSD and Pcv-aCO2/Ca-cvO2 cutoff for the evaluation of elevated ICP. Results: We included 54 patients aged mean 57.13 (standard deviation 4.02) years and 24 (44%) were male. A significant correlation was observed between ONSD and ICP (r = 0.74, P < 0.01). The AUC was 0.861 (95% CI: 0.727-0.951), with a best cutoff value of 5.62 mm. Using a cutoff of 5.62mm, ONSD had a sensitivity of 92.8%, specificity of 80.4%. The Pcv-aCO2/Ca-cvO2 ratio also significantly correlated with ICP (r = 0.70, P < 0.01). The AUC was 0.791 (95% CI: 0.673-0.889). The optimal Pcv-aCO2/Ca-cvO2 value for predicting elevated ICP was 1.98 mmHg/mL. Using a cutoff of 1.98 mmHg/mL, Pcv-aCO2/Ca-cvO2 had a sensitivity of 87.3%, specificity of 77.2%. The AUC for ONSD combined with Pcv-aCO2/Ca-cvO2 was 0.952 (95% CI: 0.869-0.971), which had a sensitivity of 95.1%, specificity of 93.9%. Conclusion: Pcv-aCO2/Ca-cvO2 combined with ONSD performed best in predicting elevated intracranial pressure of patients with TBI in a prehospital setting. Our findings provide a crucial tool to improve earlier management of these patients in prehospital care, where the availability and utilization of invasive monitoring is limited. It could lead to significant changes in how TBI patients are monitored and treated before reaching a hospital.

Intracranial pressure changes in traumatic brain injury patients undergoing unilateral decompressive craniectomy with dural expansion.

Background: The aim of this study is to assess the ICP changes induced by a unilateral fronto-temporo-parietal DC with dural expansion after moderate to severe TBI. The effect of different bone flap sizes on ICP and the neurological outcomes were also evaluated after the decompressive surgery. Methods: 52 TBI patients with clinical and radiological evidences of increased ICP were included in this prospective study. All patients received unilateral fronto-temporo-parietal DC with dural expansion and ventriculostomy at contralateral Kocher's point. Postoperatively, ICP values and the largest antero-posterior (AP) diameter of bone flap removed was measured, and the clinical outcomes were assessed using Extended Glasgow Outcome Scale (GOS-E) at discharge and 6 months after DC. Results: The median ICP significantly decreased with an average of 56.7 % reduction from the initial opening ICP. Similar ICP changes were observed in all groups. This study also found that the large bone flap group (AP diameter >15 cm) demonstrated better postoperative ICP control as compared to the small bone flap group (AP diameter 12-15 cm), although not statistically significant. The SDH and cerebral swelling groups did better in the GOS-E at 6 months after TBI compared with cerebral contusion group. Conclusion: The ICP reduction in moderate to severe TBI patients undergoing unilateral fronto-temporo-parietal DC with dural expansion occurred in accordance with decompressive steps, regardless of intracranial lesions and the surgical procedure should be performed with the bone flap size of at least 12 cm in AP diameter for adequate and sustained ICP control.

The weight of care: exploring the challenges faced by primary caregivers of children with traumatic brain injuries.

Background: Traumatic brain injury (TBI) is a leading cause of death and disability in children, yet the full impact on their primary caregivers remains largely uncharted. This study seeks to delineate the current scope of the caregiving burden and to identify the key determinants that shape it, aiming to enhance clinical interventions and caregiving approaches. Methods: We conducted a comprehensive survey of primary caregivers of pediatric TBI patients admitted to a top-tier children's hospital in China, spanning the period from January 15 to November 15, 2023. The Zarit Burden Interview (ZBI) served as the primary tool for gauging the level of caregiver burden, while the Simplified Coping Style Questionnaire (SCSQ) provided insights into their coping strategies. Results: Our survey encompassed 284 primary caregivers of TBI children. The average ZBI score for this cohort was 40.57±10.41, indicating a considerable burden. Correlational analysis uncovered robust links between the burden of caregivers and several pivotal factors: the severity of TBI (r=0.496), intensive care unit (ICU) stay (r=0.525), monthly household income (r=0.604), and reliance on negative coping mechanisms (r=0.493), all of which were statistically significant (P<0.05). Further, a multiple linear regression analysis affirmed that the severity of TBI, ICU admissions, monthly income, and negative coping styles were independent predictors of caregiver burden (P<0.05). Conclusions: The findings underscore the substantial burden shouldered by primary caregivers of TBI children. It is imperative to direct targeted support towards caregivers from economically disadvantaged backgrounds and those who tend to adopt negative coping strategies, to alleviate their burden.

The benefit of long-term methylphenidate in childhood brain injury survivorship: A review.

Survivors of childhood Acquired Brain Injury (ABI) often report chronic and debilitating neurocognitive late effects. While short-term clinical trials have demonstrated the efficacy of methylphenidate in improving neurocognitive performance within the early phases of recovery, its effectiveness over longer treatment periods remains largely unexplored. The present systematic review aims to evaluate whether methylphenidate may serve as a beneficial long-term rehabilitative strategy for improving neuropsychological outcomes in childhood ABI. Database searches were conducted in MEDLINE, PsycINFO, EMBASE, and Cochrane Library from their inception to March 2023. Studies containing a neurocognitive, psychosocial, or quality of life outcome measure were included. A purpose-developed evaluation tool was used to assess the quality of the evidence base. Six of the 1926 identified articles were included within this review. Results drew upon three clinical populations; brain tumor (n = 76), acute lymphoblastic leukemia (n = 33), and epilepsy and other EEG abnormalities (n = 166). Study durations ranged between six to 12 months. Methylphenidate was associated with sustained improvements in attentional functioning, processing speed, social skills, and quality of life, with benefits extending beyond the initial recovery phase and into future development. Side effects of methylphenidate use were reported to be mild and temporary.

Emotional awareness and expression difficulties in relation to pain experiences in people with brain injury and chronic pain: preliminary investigation.

OBJECTIVES: Preliminary examination of emotional awareness/expression relationships with pain in people with traumatic brain injury (TBI) and chronic pain (CP) and exploration of psychological factors as mediators or moderators of these relationships. METHODS: Cross-sectional study in adults (N = 59) with chronic TBI and CP using Toronto Alexithymia Scale-20 Difficulty Identifying and Describing Feelings subscales; Ambivalence over Emotional Expressiveness Questionnaire; Emotional Approach Coping Scale; PROMIS Pain Intensity and Pain Interference scales, Michigan Body Map (pain widespreadness); headache frequency; Pain Catastrophizing Scale; Brief Symptom Inventory-18 (psychological distress), and Post-traumatic Stress Checklist-Civilian. RESULTS: Difficulty Identifying Feelings was positively associated with pain intensity, pain interference, and headache frequency. Difficulty Describing Feelings was positively correlated with pain interference and headache frequency. Emotional Approach Coping was inversely correlated with headache frequency. Emotional awareness/expression relationships with pain outcomes were mediated by Pain Catastrophizing; Difficulty Describing Feelings relationships with Pain Interference and headache frequency were mediated by psychological distress; and Difficulty Describing Feelings associations with Pain Interference were mediated by post-traumatic stress. No moderators were identified. CONCLUSION: These preliminary findings suggest that emotional awareness/expression is linked to pain in adults with TBI and CP, which may be connected via pain catastrophizing and psychological distress. If longitudinal studies with larger samples produce similar findings, researchers should explore training emotional awareness/expression for possible pain management after TBI.

Engaging with discursive complexities in mental health accessibility: Implications for acquired brain injury.

The psychosocial needs of people with acquired brain injury (ABI) have been neglected based on ableist assumptions of incapability to participate in mental health treatment. Although people without disabilities benefit from evidence-based mental health supports, these treatments remain inaccessible for those with disabilities after ABI. Discursive simplifications used in dominant conceptualisations of health and disability may maintain this inaccessibility. This paper examines the role of discursive constraints in concealing the complexities of ABI recovery, undermining the gradients of mental health exclusion among different ABI subpopulations, and muddying possibilities for enhancing mental health accessibility. An alternate discourse that challenges disabling societies in service of centring the whole person is proposed. Discursive opportunities are thus created by conceptualising the objective and subjective dimensions of disability as intermeshed, providing both the motivation to incentivise mental health inclusion, as well as a method to achieve it. By recognising the unavoidable impact of bodily impairments on social participation, participatory ideals can be actualised by accommodating ABI-related disabilities in mental health treatments. The possibilities for transformative research and practice are illuminated through examples of mental health treatments that have been preliminarily adapted using accommodations, and a research agenda for realising these possibilities is proposed.

Pre- and post-therapy functional MRI connectivity in severe acute brain injury with suppression of consciousness: a comparative analysis to epilepsy features.

Severe acute brain injury (SABI) with suppressed consciousness is a major societal burden, with early prognosis being crucial for life-and-death treatment decisions. Resting-state functional MRI (rs-fMRI) is promising for prognosis and identifying epileptogenic activity in SABI. While established for SABI prognosis and seizure networks (SzNET) identification in epilepsy, the rs-fMRI use for SzNET detection in SABI is limited. This study compared evolution of SzNET and resting-state networks (RSN) pre-to-post treatment in SABI and epilepsy, hypothesizing that changes would align with clinical evolution. Therapies included epilepsy surgery for the epilepsy group and antiseizure medication for the SABI group. Independent component analysis (ICA) was used to identify SzNET and RSNs in all rs-fMRI. High-frequency BOLD (HF-BOLD), an ICA power spectrum-based index, quantified RSN and SzNET changes by the patient. Confidence intervals measured HF-BOLD changes pre-to-post-therapy. Baseline HF-BOLD and HF-BOLD changes were compared using linear-mixed models and interaction tests. Five SABI and ten epilepsy patients were included. SzNET were identified in all SABI's pre-therapy rs-fMRI. The clinical changes in SABI and epilepsy were consistent with rs-fMRI findings across groups. HF-BOLD reduced in the epilepsy group RSN post-therapy (-0.78, 95% CI -3.42 to -0.33), but the evidence was insufficient to determine an HF-BOLD reduction in SABI patients or SzNET. The HF-BOLD change trend in pre-to-post epilepsy surgery scans paralleled the clinical improvement, suggesting that the power spectrum may quantify the degree of abnormality on ICA-derived networks. Despite limitations such as small sample sizes, this exploratory study provides valuable insights into network dysfunction in SABI and epilepsy.

A Narrative Review of Post-traumatic Neuroinflammation: Relevance to Pediatrics.

This is a narrative review that explores the complex interaction between post-traumatic neuroinflammation and its importance in pediatric traumatic brain injuries (TBIs). For immediate and long-term consequences of TBI, neuroinflammation, manifested by activation of microglia and astrocytes, secretion of pro-inflammatory cytokines, as well as breakdown of the blood-brain barrier, are critical factors. While inflammation is an essential part of the brain's repair systems, excessive or prolonged neuroinflammation can lead to more significant neuronal damage, which, in turn, causes persistent cognitive and behavioral deficits over time. In this regard, the paper synthesizes existing evidence concerning molecular and cellular mechanisms that underlie neuroinflammation in relation to TBI among children, paying attention to age disparities in inflammatory response and their implications for treatment and recovery. Furthermore, it explores how targeted anti-inflammatory therapies are highly likely to improve outcomes for pediatric patients. The outcomes emphasize that there is a need for a more comprehensive understanding of child neuroinflammatory processes and age-specific therapeutic approaches aimed at lessening the effects' negative impacts after brain injury occurs.

Neonatal encephalopathy multiorgan scoring systems: systematic review.

Introduction: Neonatal encephalopathy (NE) is a condition with multifactorial etiology that causes multiorgan injury to neonates. The severity of multiorgan dysfunction (MOD) in NE varies, with therapeutic hypothermia (TH) as the standard of care. The aim is to identify current approaches used to assess and determine an optimum scoring system for MOD in NE. Methods: The systematic review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search was conducted using PubMed, EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, and CINAHL for studies of scoring systems for MOD in NE. Results: The search yielded 628 articles of which 12 studies were included for data extraction and analysis. Five studies found a positive correlation between the severity of NE and MOD. There was significant heterogeneity across the scoring systems, including the eligibility criteria for participants, the methods assessing specific organ systems, the length of follow-up, and adverse outcomes. The neurological, hepatic, cardiovascular, respiratory, hematological, and renal systems were included in most studies while the gastrointestinal system was only in three studies. The definitions for hepatic, renal, and respiratory systems dysfunction were most consistent while the cardiovascular system varied the most. Discussion: A NE multiorgan scoring system should ideally include the renal, hepatic, respiratory, neurological, hematological, and cardiovascular systems. Despite the heterogeneity between the studies, these provide potential candidates for the standardization of MOD scoring systems in NE. Validation is needed for the parameters with adequate length of follow-up beyond the neonatal period. Additionally, the evaluation of MOD may be affected by TH considering its multiorgan effects.

Spectrum of delayed post-hypoxic leukoencephalopathy syndrome: A systematic review.

BACKGROUND: Delayed post hypoxic leukoencephalopathy syndrome (DPHLS), also known as Grinker's myelinopathy, is a rare but significant neurological condition that manifests days to weeks after a hypoxic event. Characterized by delayed onset of neurological and cognitive deficits, DPHLS presents substantial diagnostic and therapeutic challenges. AIM: To consolidate current knowledge on pathophysiology, clinical features, diagnostic approaches, and management strategies for DPHLS, providing a comprehensive overview and highlighting gaps for future research. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines, we systematically searched PubMed, ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy. Inclusion criteria were original research articles, case reports, and case series involving human subjects with detailed clinical, neuroimaging, or pathological data on DPHLS. Data were extracted on study characteristics, participant demographics, clinical features, neuroimaging findings, pathological findings, treatment, and outcomes. The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist. RESULTS: A total of 73 cases were reviewed. Common comorbidities included schizoaffective disorder, bipolar disorder, hypertension, and substance use disorder. The primary causes of hypoxia were benzodiazepine overdose, opioid overdose, polysubstance overdose, and carbon monoxide (CO) poisoning. Symptoms frequently include decreased level of consciousness, psychomotor agitation, cognitive decline, parkinsonism, and encephalopathy. Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter, sometimes involving the basal ganglia and the globus pallidus. Magnetic resonance spectroscopy often showed decreased N-acetylaspartate, elevated choline, choline-to-creatinine ratio, and normal or elevated lactate. Treatment is often supportive, including amantadine, an antioxidant cocktail, and steroids. Hyperbaric oxygen therapy may be beneficial in those with CO poisoning. Parkinsonism was often treated with levodopa. Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits. CONCLUSION: DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations. Early recognition and appropriate management are crucial to improving patient outcomes. Future research should focus on standardizing diagnostic criteria, using advanced imaging techniques, and exploring therapeutic interventions to improve understanding and treatment of DPHLS. Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

External evaluation of Brain Injury Guideline (BIG) low risk criteria for traumatic brain injury.

BACKGROUND: Fewer than 20 % of traumatic brain injury (TBI) cases with traumatic intracranial hemorrhage (ICH) result in clinical deterioration. The Brain Injury Guideline (BIG) criteria were published in 2014 and categorize patients with TBI into three risk groups (BIG 1, 2, and 3) based on CT scan findings, neurological examination, anti-coagulant/platelet medications, and intoxication. Early data is promising, suggesting no instances of neurosurgical intervention or death in the low-risk BIG1 category within 30 days. We sought to externally validate the BIG criteria and identify patients with TBI at low risk of clinical deterioration. We hypothesized that patients meeting the BIG1 low risk criteria have less than a 1 % risk of death or neurosurgical intervention. METHODS: We performed a retrospective cohort study of a level 1 trauma center's trauma registry records from 2011 to 2022 to identify patients with head trauma. We abstracted demographics, injury characteristics, clinical course, CT imaging results, and outcomes, and we categorized patients according to the BIG criteria. The Clopper-Pearson Exact method was used to estimate outcome frequency with confidence intervals. The primary outcome was death or neurosurgical intervention within 30 days. Secondary outcomes included progression on repeat head CT (RHCT), ICU admission with neurocritical care intervention, and TBI-related hospital readmission within 30 days. RESULTS: A total of 1714 patients with TBI with ICH were identified from the trauma registry. 325 patients were excluded due to missing data, pregnancy, incarceration, polytrauma, or GCS < 13, leaving 1389 for analysis. 193 patients (13.9 %) were classified as BIG1. No patients classified as BIG1 experienced the primary outcome measures of death or neurosurgical intervention (95 % confidence interval [CI]: 0 %-1.9 %). The number of patients who experienced the secondary outcome measures of progression on RHCT, ICU admission with neurocritical care intervention, or TBI-related hospital readmission within 30 days were 9 (4.7 %, 95 % CI: 2.2 %-8.7 %), 1 (0.5 %, 95 % CI: 0 %-2.9 %), and 4 (2.1 %, 95 % CI: 0.6 %-5.2 %), respectively. CONCLUSION: BIG1 criteria identified a low-risk subset of patients with TBI with ICH. However, an upper 95 % CI of 1.9 % does not exclude the risk of neurologic deterioration being <1 %. Validation of these criteria in larger cohorts is warranted.

Chronic Traumatic Encephalopathy: A Comprehensive Narrative Review of Its Biomarkers.

Chronic traumatic encephalopathy (CTE) is a progressive and fatal neurological disorder linked to repeated traumatic brain injuries (TBIs), including concussions and blows to the head. This condition is characterized by the accumulation of abnormally structured hyperphosphorylated tau proteins (p-tau), forming neurofibrillary tangles, astrocytic tangles, and neurites in the brain. CTE is often diagnosed post-mortem, making it challenging to diagnose and predict its progression in living individuals. Despite recent advancements, no definitive pathological, radiological, or neurobiological marker consistently shows promise in diagnosing and predicting the disease. This review aims to summarize the available techniques and advancements in imaging-based, genetic, neuropsychological, and fluid biomarkers for CTE, evaluating their specificity and sensitivity. It will also highlight the limitations of each marker in diagnosing CTE and provide future research directions to enhance the accuracy of CTE diagnosis in living individuals.

Evidence-Based Medical Management and Physiotherapy Rehabilitation in Pediatric Traumatic Brain Injury: A Narrative Review.

Children between the ages of one and 18 are at a heightened risk of death and impairment due to traumatic brain injury (TBI). TBI can be deadly and is usually categorized as mild, moderate, or severe according to the Glasgow Coma Scale (GCS). For individuals with a TBI and an abnormal GCS, the preferred modality is non-contrast CT of the head. This review focuses on the medical treatment and rehabilitation of children with TBI and their outcomes. This was searched in databases such as PubMed, Google Scholar, and EMBASE. The literature search criteria included "traumatic brain injury AND physiotherapy rehabilitation OR medical treatment," with additional filters applied, including full text, both male and female, ages below 18 years, and publications from 2012 to 2024. This study conducted research on the treatment and rehabilitation of children with TBI. Ten randomized clinical trials, non-randomized trials, and longitudinal cohort study randomized trials met the inclusion criteria, which include hyperbaric oxygen therapy, melatonin, nabiximols, psycho-educational intervention, online therapy, the virtual reality rehabilitation program, and conventional occupational therapy. The results show significant improvement in forearm supination, performance in daily living, quality of life, reduced anger, improved school functioning, improvement in TBI conditions, reduced hospital stay, activity facilitating recovery, and reduced prolonged symptoms. This review has addressed the effectiveness of various medical management and rehabilitation strategies, which are important in TBI and aim to mitigate post-traumatic/concussion impact and improve quality of life. Articles regarding children's TBI rehabilitation are comparatively few. One possible solution to this issue would be to encourage further rehabilitation intervention trials.

Behavioral Assays for Comprehensive Evaluation of Cognitive and Neuropsychiatric Comorbidities of Traumatic Brain Injury and Chronic Neurological Disorders.

Neurological deficits, psychiatric disorders, and cognitive impairments often accompany stroke, brain injury, epilepsy, and many neurological disorders, which present intricate comorbidities that challenge recognition and management. There are many tools and paradigms for evaluating learning, memory, anxiety, and depression-like behaviors in lab animal models of brain disorders. However, there is a significant gap between clinical observations and experimental models, which limit understanding of the complex interplay between chronic brain conditions and their impact on cognitive dysfunction and psychiatric impairments. This article describes an overview of experimental rationale, methods, protocols, and strategies for evaluating sensorimotor, affective and cognitive-associated comorbid behaviors in epilepsy, traumatic brain injury (TBI), stroke, spinal cord injury (SCI), and many other neurological disorders. First, we delve into clinical evidence elucidating the profound impact of comorbidities, e.g., psychiatric disorders and cognitive deficits, in individuals with epilepsy. Then, we discuss diverse approaches to assess these comorbidities in experimental models of brain diseases. Finally, we explore the methodologies for assessing motor function, sensorimotor, behavior, and psychiatric health. We cover strategies and protocols enabling these assays, including implementing behavioral paradigms to assess learning and memory, anxiety, and depression-like behaviors in rodents in health and disease conditions. It is essential to consider a comprehensive battery of tests to investigate various behavioral deficits, considering environment, age, and sex differences relevant to the disease, such as TBI, SCI, epilepsy, stroke, and other complex neurological conditions. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.

Criteria for neurosurgical treatment of children and adolescents with traumatic brain injury in a Brazilian level 1 trauma center.

OBJECTIVE: Considering Glasgow Coma Scale (GCS) scores and brain CT scans in a group of children and adolescents with traumatic brain injury (TBI), the scope of this study was to identify the criteria established for the indication of emergency neurosurgical treatment in a level 1 trauma center. METHODS: This was a cross-sectional study with consecutive review of medical records of children and adolescents < 17 years with TBI who were hospitalized and underwent neurosurgical treatment between January 2016 and December 2023. Two groups were formed for analysis: patients with GCS scores ≤ 8 versus patients with GCS scores > 8. Based on the GCS score and brain CT scan of each patient, the authors investigated the criteria established for the surgical indications in this group. RESULTS: In the period considered for the study, 376 children and adolescents with TBI were hospitalized and 31% required neurosurgical treatment. The median age was 5 years (interquartile range 1-11 years) and there was a predominance of males (68%). Home accidents predominated in 77% of children < 5 years of age, whereas road accidents predominated among those older than 5 (47%). Diffuse brain lesions on CT scans predominated in patients with GCS scores ≤ 8 when compared to the group with GCS scores > 8 (89% vs 19%; p < 0.0001). Regarding neurosurgical access, decompressive craniectomies (70%) and invasive intracranial pressure monitoring (44%) prevailed among patients with GCS scores ≤ 8, whereas craniotomies for drainage of intracranial hematomas (70%) and surgical correction of depressed skull fracture (21%) prevailed among those with GCS scores > 8. CONCLUSIONS: Based on the GCS scores and CT scans, the authors were able to define the criteria used for neurosurgical indications in a Brazilian level 1 trauma center. They found a high prevalence of decompressive craniectomy in patients with severe TBI in their department due to the irregular supply of disposable catheters necessary for intracranial pressure monitoring.

Wartime penetrating traumatic brain injury of the anterior skull base involving the paranasal sinuses: a single-center, first-year experience from Dnipro, Ukraine.

OBJECTIVE: Since February 2022, the number of casualties in the Russian-Ukrainian war have dramatically increased, with a high incidence of penetrating traumatic brain injuries (pTBIs). To date, there has been limited evaluation of pTBI of the anterior skull base involving the paranasal sinuses. The objective of this study was to highlight the authors' experience with this injury pattern and identify specific factors associated with favorable short-term (1-month) outcome and survival. METHODS: The authors conducted a single-institution retrospective review of patient data collected from the 1st year of the Russian-Ukrainian war at a frontline civilian Ukrainian hospital. To prevent complications from conservative treatment of pTBI with paranasal sinus injury, a protocol of early primary neurosurgical treatment including debridement/hematoma evacuation, repair of dural defects with vascularized pericranial flaps, and titanium plating of external/skull base defects was implemented. Using 1-month postoperative Glasgow Outcome Scale scores, the authors defined a favorable outcome as good recovery/moderate disability and a poor outcome as severe disability/vegetative state/death. Patient demographics, injury characteristics, imaging findings, and postoperative complications were assessed. Logistic regression models were used to estimate the effect of patient characteristics on unfavorable outcome or survival. RESULTS: From February 2022 to February 2023, there were 141 pTBIs (20%) involving the paranasal sinuses, 134 (95%) due to blast fragmentation. One hundred eighteen patients (84%) had a favorable outcome. Most patients with pTBIs (69%) had other nonbrain-related injuries. While 48 patients (34%) presented with preoperative CSF leak, only 1 patient (0.7%) had persistent postoperative CSF leak, which was managed with lumbar drainage. High admission Glasgow Coma Scale (GCS) score, favorable injury lateralization (single hemisphere involved), and low Injury Severity Score (ISS) were associated with significantly increased odds of favorable short-term outcome, whereas high admission GCS scores and no midline shift were associated with significantly increased odds of survival. CONCLUSIONS: This was the largest single-year study on neurosurgical treatment of wartime pTBI involving the paranasal sinuses. Implementation of primary neurosurgical intervention at the time of presentation demonstrated promising early results and a shift away from expectant management of this injury pattern. The association of high admission GCS score, low ISS, favorable injury lateralization, and no midline shift on favorable short-term outcomes or survival has not been previously documented with this injury pattern.

Daidzein ameliorates experimental traumatic brain injury-induced neurological symptoms by suppressing oxidative stress and apoptosis.

Traumatic brain injury (TBI) causes deficits in neurological function, induces pathological changes, and increases oxidative stress. The current investigation aimed to determine Daidzein's neuroprotective potential in experimental TBI. Initially, the HT-22 cell line exposed to H2O2 underwent in vitro examination, and the results showed that Daidzein had a neuroprotective effect evident from enhanced cell viability and decreased NO generation. Using three different Daidzein doses-1 mg/kg, 5 mg/kg, and 10 mg/kg-in the in vivo experiment, the potential of Daidzein was evaluated against TBI. The neurological severity score (NSS), kondziela's screen test, and elevated plus maze showed improvements after treatment with Daidzein manifested by decreased score, enhanced motor coordination, and anti-anxiety effects. Additionally, Daidzein improved mechanical allodynia and restored the breakdown of the blood-brain barrier. The FTIR spectral analysis showed restoration of the biochemical compositional changes. Furthermore, H & E and Toluidine blue staining revealed an improvement in the histopathological alterations. The RT-qPCR revealed an increase in mRNA expression level of Nrf2, HO-1, and Bcl-2 and the downregulation of Keap-1, Bax and Cleaved caspase-3 expressions. Thus, exhibiting its antioxidant and antiapoptotic potential. The RT-qPCR also manifested a decrease in mRNA expression of GFAP and Iba-1. Further immunohistochemistry results indicated Daidzein's antioxidant and antiapoptotic properties by upregulating Nrf2 and downregulating cleaved caspase-3. Daidzein also lowered the apoptosis index and improved neuronal survival evidenced by flow cytometric analysis. In addition to this, Daidzein notably increased the antioxidant enzyme levels and decreased the oxidative stress markers. The current study's findings point to the neuroprotective potential of the phytoestrogen Daidzein as it lessened neurological abnormalities, decreased oxidative stress, and lowered proapoptotic protein expression.

Machine learning models of cerebral oxygenation (rcSO2) for brain injury detection in neonates with hypoxic-ischaemic encephalopathy.

The present study was designed to test the potential utility of regional cerebral oxygen saturation (rcSO2) in detecting term infants with brain injury. The study also examined whether quantitative rcSO2 features are associated with grade of hypoxic ischaemic encephalopathy (HIE). We analysed 58 term infants with HIE (>36 weeks of gestational age) enrolled in a prospective observational study. All newborn infants had a period of continuous rcSO2 monitoring and magnetic resonance imaging (MRI) assessment during the first week of life. rcSO2 Signals were pre-processed and quantitative features were extracted. Machine-learning and deep-learning models were developed to detect adverse outcome (brain injury on MRI or death in the first week) using the leave-one-out cross-validation approach and to assess the association between rcSO2 and HIE grade (modified Sarnat - at 1 h). The machine-learning model (rcSO2 excluding prolonged relative desaturations) significantly detected infant MRI outcome or death in the first week of life [area under the curve (AUC) = 0.73, confidence interval (CI) = 0.59-0.86, Matthew's correlation coefficient = 0.35]. In agreement, deep learning models detected adverse outcome with an AUC = 0.64, CI = 0.50-0.79. We also report a significant association between rcSO2 features and HIE grade using a machine learning approach (AUC = 0.81, CI = 0.73-0.90). We conclude that automated analysis of rcSO2 using machine learning methods in term infants with HIE was able to determine, with modest accuracy, infants with adverse outcome. De novo approaches to signal analysis of NIRS holds promise to aid clinical decision making in the future. KEY POINTS: Hypoxic-induced neonatal brain injury contributes to both short- and long-term functional deficits. Non-invasive continuous monitoring of brain oxygenation using near-infrared- spectroscopy offers a potential new insight to the development of serious injury. In this study, characteristics of the NIRS signal were summarised using either predefined features or data-driven feature extraction, both were combined with a machine learning approach to predict short-term brain injury. Using data from a cohort of term infants with hypoxic ischaemic encephalopathy, the present study illustrates that automated analysis of regional cerebral oxygen saturation rcSO2, using either machine learning or deep learning methods, was able to determine infants with adverse outcome.