Management Of Traumatic Brain Injury Research Articles

Comparative efficacy analysis of mannitol and hypertonic saline in the management of traumatic brain injury: a scientific exploration of neuroprotective strategies

Comparative efficacy analysis of mannitol and hypertonic saline in the management of traumatic brain injury: a scientific exploration of neuroprotective strategies

Safety evaluation of adenosine, lidocaine and magnesium (ALM) intranasal therapy toward human nasal epithelial cells in vitro.

Adenosine, lidocaine and Mg2+ (ALM) solution is an emerging therapy that reduces secondary injury after intravenous administration in experimental models of traumatic brain injury (TBI). Intranasal delivery of ALM may offer an alternative route for rapid, point-of-care management of TBI. As a preliminary safety screen, we evaluated whether ALM exerts cytotoxic or inflammatory effects on primary human nasal epithelial cells (pHNEC) in vitro. Submerged monolayers and air-liquid interface cultures of pHNEC were exposed to media only, normal saline only, therapeutic ALM or supratherapeutic ALM for 15 or 60 min. Safety was measured through viability, cytotoxicity, apoptosis, cellular and mitochondrial stress, and inflammatory mediator secretion assays. No differences were found in viability or cytotoxicity in cultures exposed to saline or ALM for up to 60 min, with no evidence of apoptosis after exposure to supratherapeutic ALM concentrations. Despite comparable inflammatory cytokine secretion profiles and mitochondrial activity, cellular stress responses were significantly lower in cultures exposed to ALM than saline. In summary, data show ALM therapy has neither adverse toxic nor inflammatory effects on human nasal epithelial cells, setting the stage for in vivo toxicity studies and possible clinical translation of intranasal ALM therapy for TBI treatment.

A commentary on "Management of Traumatic Brain Injury in Africa: challenges and opportunities" (Int J Surg. 2024 Apr 4; Online ahead of print.).

A commentary on "Management of Traumatic Brain Injury in Africa: challenges and opportunities" (Int J Surg. 2024 Apr 4; Online ahead of print.).

Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study

IntroductionIn light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their...

Deleterious effect of sustained neuroinflammation in pediatric traumatic brain injury

IntroductionDespite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model. MethodsPediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45. ResultsTBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors. ConclusionsWe show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI.

Early GFAP and UCH-L1 point-of-care biomarker measurements for the prediction of traumatic brain injury and progression in patients with polytrauma and hemorrhagic shock

OBJECTIVE Traumatic brain injury (TBI) and hemorrhage are responsible for the largest proportion of all trauma-related deaths. In polytrauma patients at risk of hemorrhage and TBI, the diagnosis, prognosis, and management of TBI remain poorly characterized. The authors sought to characterize the predictive capabilities of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) measurements in patients with hemorrhagic shock with and without concomitant TBI. METHODS The authors performed a secondary analysis on serial blood samples derived from a prospective observational cohort study that focused on comparing early whole-blood and component resuscitation. A convenience sample of patients was used in which samples were collected at three time points and the presence of TBI or no TBI via CT imaging was documented. GFAP and UCH-L1 measurements were performed on plasma samples using the i-STAT Alinity point-of-care platform. Using classification tree recursive partitioning, the authors determined the measurement cut points for each biomarker to maximize the abilities for predicting the diagnosis of TBI, Rotterdam CT imaging scores, and 6-month Glasgow Outcome Scale–Extended (GOSE) scores. RESULTS Biomarker comparisons demonstrated that GFAP and UCH-L1 measurements were associated with the presence of TBI at all time points. Classification tree analyses demonstrated that a GFAP level > 286 pg/ml for the sample taken upon the patient’s arrival had an area under the receiver operating characteristic curve of 0.77 for predicting the presence of TBI. The classification tree results demonstrated that a cut point of 3094 pg/ml for the arrival GFAP measurement was the most predictive for an elevated Rotterdam score on the initial and second CT scans and for TBI progression between scans. No significant associations between any of the most predictive cut points for UCH-L1 and Rotterdam CT scores or TBI progression were found. The predictive capabilities of UCH-L1 were limited by the range allowed by the point-of-care platform. Arrival GFAP cut points remained strong independent predictors after controlling for all potential polytrauma confounders, including injury characteristics, shock severity, and resuscitation. CONCLUSIONS Early measurements of GFAP and UCH-L1 on a point-of-care device are significantly associated with CT-diagnosed TBI in patients with polytrauma and shock. Early elevated GFAP measurements are associated with worse head CT scan Rotterdam scores, TBI progression, and worse GOSE scores, and these associations are independent of other injury attributes, shock severity, and early resuscitation characteristics.

A Modern Approach to the Treatment of Traumatic Brain Injury.

Background: Traumatic brain injury manifests itself in various forms, ranging from mild impairment of consciousness to severe coma and death. Traumatic brain injury remains one of the leading causes of morbidity and mortality. Currently, there is no therapy to reverse the effects associated with traumatic brain injury. New neuroprotective treatments for severe traumatic brain injury have not achieved significant clinical success. Methods: A literature review was performed to summarize the recent interdisciplinary findings on management of traumatic brain injury from both clinical and experimental perspective. Results: In the present review, we discuss the concepts of traditional and new approaches to treatment of traumatic brain injury. The recent development of different drug delivery approaches to the central nervous system is also discussed. Conclusions: The management of traumatic brain injury could be aimed either at the pathological mechanisms initiating the secondary brain injury or alleviating the symptoms accompanying the injury. In many cases, however, the treatment should be complex and include a variety of medical interventions and combination therapy.

Comparison of mannitol and hypertonic saline solution for the treatment of suspected brain herniation during prehospital management of traumatic brain injury patients.

Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain herniation. The initiation of hyperosmolar therapy to reduce ICH and brain herniation is recommended. Whether mannitol or hypertonic saline solution (HSS) should be preferred is unknown. The objective of this study is to assess whether HSS, compared with mannitol, is associated with improved survival in adult trauma patients with TBI and mydriasis. A retrospective observational cohort study using the French Traumabase national registry to compare the ICU mortality of patients receiving either HSS or mannitol. Patients aged 16 years or older with moderate to severe TBI who presented with mydriasis during prehospital management were included. We performed propensity score matching on a priori selected variables [i.e. age, sex and initial Coma Glasgow Scale (GCS)] with a ratio of 1 : 3 to ensure comparability between the two groups. The primary outcome was ICU mortality. The secondary outcomes were regression of pupillary abnormality during prehospital management, pulsatility index and diastolic velocity on transcranial Doppler within 24 h after TBI, early ICU mortality (within 48 h), ICU and hospital length of stay. Of 31 579 patients recorded in the registry between 2011 and 2021, 1417 presented with prehospital mydriasis and were included: 1172 (82.7%) received mannitol and 245 (17.3%) received HSS. After propensity score matching, 720 in the mannitol group matched 240 patients in the HSS group. Median age was 41 years [interquartile ranges (IQR) 26-60], 1058 were men (73%) and median GCS was 4 (IQR 3-6). No significant difference was observed in terms of characteristics and prehospital management between the two groups. ICU mortality was lower in the HSS group (45%) than in the mannitol group (54%) after matching [odds ratio (OR) 0.68 (0.5-0.9), P = 0.014]. No differences were identified between the groups in terms of secondary outcomes. In this propensity-matched observational study, the prehospital osmotherapy with HSS in TBI patients with prehospital mydriasis was associated with a lower ICU mortality compared to osmotherapy with mannitol.

Management of traumatic brain injury in India: A protocol for systematic review and meta-analysis

Abstract* Introduction This systematic review and meta-analysis protocol aims to evaluate the management of traumatic brain injury (TBI) in India, addressing a critical gap in the understanding and treatment of TBI in low- and middle-income countries (LMICs). Despite advancements in healthcare focusing primarily on communicable diseases, TBI remains a leading cause of death and disability worldwide, significantly affecting the quality of life of patients and their families. Recent interest has surged in platelet-rich plasma (PRP) as a novel treatment for TBI, necessitating a comprehensive review of its therapeutic benefits. Methodology The study will source articles from PubMed, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials, targeting a range of studies including randomized controlled trials (RCTs), observational studies, and cohort studies. The review will exclude case series, review articles, and studies not reported in English. The primary aim is to collate evidence-based data on TBI management, with particular focus on the Indian healthcare context, evaluating the efficacy of current treatments and the potential role of PRP in enhancing neurological function and recovery post-TBI. Data management will involve a rigorous selection process, with independent reviewers conducting initial screenings and resolving discrepancies through discussion or arbitration. A PRISMA flow diagram will illustrate the study selection procedure, and a standardized form will be used for data extraction, ensuring thoroughness and consistency. Conclusion By highlighting current knowledge gaps, this systematic review and meta-analysis will guide future research directions and clinical practice, potentially revolutionizing TBI management strategies in LMICs. This protocol underscores the necessity for high-quality, evidence-based approaches to TBI treatment, aiming to improve patient outcomes through enhanced management practices.

Therapeutic Hypothermia Compared with Normothermia in Adults with Traumatic Brain Injury; Functional Outcome, Mortality, and Adverse Effects: A Systematic Review and Meta-Analysis.

The main focus of traumatic brain injury (TBI) management is prevention of secondary injury. Therapeutic hypothermia (TH), the induction of a targeted low core body temperature, has been explored as a potential neuroprotectant in TBI. The aim of this article is to synthesize the available clinical data comparing the use of TH with the use of normothermia in TBI. A systematic search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized clinical trials including one or more outcome of interest associated with TH use in TBI. Independent reviewers evaluated quality of the studies and extracted data on patients with TBI undergoing TH treatment compared with those undergoing normothermia treatment. Pooled estimates, confidence intervals (CIs), and risk ratios (RRs) or odds ratios were calculated for all outcomes. A total of 3,909 patients from 32 studies were eligible for analysis. Pooled analysis revealed a significant benefit of TH on mortality and functional outcome (RR 0.81, 95% CI 0.68-0.96, I2 = 41%; and RR 0.77; 95% CI 0.67-0.88, I2 = 68%, respectively). However, subgroup analysis based on risk of bias showed that only studies with a high risk of bias maintained this benefit. When divided by cooling method, reduced poor functional outcome was seen in the systemic surface cooling and cranial cooling groups (RR 0.68, 95% CI 0.59-0.79, I2 = 35%; and RR 0.44, 95% CI 0.29-0.67, I2 = 0%), and no difference was seen for the systemic intravenous or gastric cooling group. Reduced mortality was only seen in the systemic surface cooling group (RR 0.63, 95% CI 0.53-0.75, I2 = 0%,); however, this group had mostly high risk of bias studies. TH had an increased rate of pneumonia (RR 1.24, 95% CI 1.10-1.40, I2 = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09-2.44, I2 = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05-3.01, I2 = 21%). Once separated by low and high risk of bias, we saw no difference in these complications in the groups with low risk of bias. Overall quality of the evidence was moderate for mortality, functional outcome, and pneumonia and was low for coagulation abnormalities and cardiac arrhythmias. With the addition of several recent randomized clinical trials and a thorough quality assessment, we have provided an updated systematic review and meta-analysis that concludes that TH does not show any benefit over normothermia in terms of mortality and functional outcome.

Blood Biomarkers for the Management of Mild Traumatic Brain Injury in Clinical Practice.

Despite the use of validated guidelines in the management of mild traumatic brain injury (mTBI), processes to limit unnecessary brain scans are still not sufficient and need to be improved. The use of blood biomarkers represents a relevant adjunct to identify patients at risk for intracranial injury requiring computed tomography (CT) scan. Biomarkers currently recommended in the management of mTBI in adults and children are discussed in this review. Protein S100 beta (S100B) is the best-documented blood biomarker due to its validation in large observational and interventional studies. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminal hydrolase L-1 (UCH-L1) have also recently demonstrated their usefulness in patients with mTBI. Preanalytical, analytical, and postanalytical performance are presented to aid in their interpretation in clinical practice. Finally, new perspectives on biomarkers and mTBI are discussed. In adults, the inclusion of S100B in Scandinavian and French guidelines has reduced the need for CT scans by at least 30%. S100B has significant potential as a diagnostic biomarker, but limitations include its rapid half-life, which requires blood collection within 3 h of trauma, and its lack of neurospecificity. In 2018, the FDA approved the use of combined determination of GFAP and UCH-L1 to aid in the assessment of mTBI. Since 2022, new French guidelines also recommend the determination of GFAP and UCH-L1 in order to target a larger number of patients (sampling within 12 h post-injury) and optimize the reduction of CT scans. In the future, new cut-offs related to age and promising new biomarkers are expected for both diagnostic and prognostic applications.

Trends in Traumatic Brain Injuries During the COVID-19 Pandemic: A Single-Center Review of Patient Charts From Pakistan.

Introduction A traumatic brain injury (TBI) is one of the leading causes of injury-related deaths, making it a public health concern of extreme importance. In a developing country such as Pakistan, TBIs aresignificantly underreported, with the treatment frequently being delayed and inadequate, especially in rural healthcare setups all across the country. This concern is further magnified by insufficient epidemiological data on TBIs available in Pakistan. The coronavirus disease 2019 (COVID-19) pandemic brought consequential changes to the healthcare system with the priority shifting towardCOVID-19 patients, resulting in considerable changes to the workflow and management of TBIs. The primary objective of this study is to offer valuable insights into the epidemiology of TBIs in Pakistan and its relationship with the impact of the COVID-19 pandemic. Methods A retrospective study was conductedat a tertiary care center in a metropolitan city in Pakistan. Patient charts were reviewed from January to August 2020, and data was extracted including demographics, clinical presentation, management, and outcomes for cases of TBI. Results The total number of patients is 2126, male 78% and female 21.4%. The mean age of the patients was 28.85. The state of admissions at the hospital is at 99.7% for EME admissions and 0.282% for OPD admissions. Participants presented with loss of consciousness (70.7%), nosebleeds, (53.2%), vomiting (69.0%), and seizures (11.5%). The majority (51.1%) were related to road traffic accidents, followed by falls (20.7%), and assaults (4%). While 1202 (58.5%) of these were managed conservatively, others underwent surgical treatment in the form of craniotomy (28.0%), Burr holes (3.20%), and fracture elevation and repair (10.5%). A decrease in the number of reported TBI cases was observed with lockdown implementation in Pakistan. Conclusion The transportation sector in Pakistan was severely affected by the COVID-19 pandemic, leading to a decline in road traffic injuriesand TBIs. Stringent mobility constraints and changes in societal and cultural norms have contributed to this reduction.

Comparison of GFAP and UCH-L1 Measurements Using Two Automated Immunoassays (i-STAT® and Alinity®) for the Management of Patients with Mild Traumatic Brain Injury: Preliminary Results from a French Single-Center Approach.

The measurement of blood glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) may assist in the management of mild traumatic brain injury (mTBI). This study aims to compare GFAP and UCH-L1 values measured using a handheld device with those measured using a core laboratory platform. We enrolled 230 mTBI patients at intermediate risk of complications. Following French guidelines, a negative S100B value permits the patient to be discharged without a computed tomography scan. Plasma GFAP and UCH-L1 levels were retrospectively measured using i-STAT® and Alinity® i analyzers in patients managed within 12 h post-trauma. Our analysis indicates a strong correlation of biomarker measurements between the two analyzers. Cohen's kappa coefficients and Lin's concordance coefficients were both ≥0.7, while Spearman's correlation coefficient was 0.94 for GFAP and 0.90 for UCH-L1. Additionally, the diagnostic performance in identifying an intracranial lesion was not significantly different between the two analyzers, with a sensitivity of 100% and specificity of approximately 30%. GFAP and UCH-L1 levels measured using Abbott's i-STAT® and Alinity® i platform assays are highly correlated both analytically and clinically in a cohort of 230 patients managed for mTBI according to French guidelines.

Effect of ethanol extract of nigella sativa L seeds and propofol on BDNF protein level as neuroplasticity and neuroprotection of traumatic brain injury in rats

Background Traumatic brain injury (TBI) is a change in brain function or evidence of brain pathology caused by external mechanical forces. Brain Derived Neurotrophic Factor (BDNF) is a neurotropin that functions as a neuron protective. Nigella sativa L is reported to have an antioxidant effect, administration of Nigella Sativa L to rats treated with ischemia-reperfusion brain injury. Propofol is an anesthetic agent frequently used intravenously in the management of TBI. The effect of propofol on brain tissue after TBI may be neuroprotective. We aimed to compare the potential of Nigella sativa L and propofol as neuroplasticity and neuroprotection in rats with TBI. Methods This was a laboratory experimental animal model with the post-test only control group design, namely measuring the effect of treatment by comparing the five groups of rats consisting of 30 rats. BDNF levels in rat brain tissue were collected at day 7 of treatment and measured by ELISA. Results The average BDNF protein levels per group, namely G1 (221,243 pg/mL), G2 (172,139 pg/mL), G3 (255,483 pg/mL), G4 (227,089 pg/mL), and G5 (272,603 pg/mL) respectively. Based on the ANOVA statistic, p-value = 0.032 (there was a significant difference between groups), with the Levene Test (0.077) or having variance between the same groups, sequentially the difference in average BDNF protein levels of the five groups is G5>G3>G4>G1>G2, meaning that the combination of Nigella sativa and propofol has more potential to increase BDNF protein levels than Nigella sativa, and Nigella sativa has more potential than propofol. Conclusion We concluded that both nigella sativa and propofol have the potential to increase BDNF protein levels. Nigella Sativa L had a better effect than propofol in repairing damaged neuron cells (neuroplasticity) and increasing BDNF protein levels (neuroprotection) for 7 days of administration in rat traumatic brain injury.

Atox1 protects hippocampal neurons after traumatic brain injury via DJ-1 mediated anti-oxidative stress and mitophagy

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation. The expression of Atox1 was significantly diminished following TBI, while mice with overexpressed Atox1 exhibited a more preserved hippocampal structure and reduced levels of oxidative stress post-TBI. Furthermore, the mice displayed notable impairments in learning and memory functions after TBI, which were ameliorated by the overexpression of Atox1. In the stretch injury model of HT-22 cells, overexpression of Atox1 mitigated oxidative stress by preserving the normal morphology and network connectivity of mitochondria, as well as facilitating the elimination of damaged mitochondria. Mechanistically, co-immunoprecipitation and mass spectrometry revealed the binding of Atox1 to DJ-1. Knockdown of DJ-1 in HT-22 cells significantly impaired the antioxidant capacity of Atox1. Mutations in the copper-binding motif or sequestration of free copper led to a substantial decrease in the interaction between Atox1 and DJ-1, with overexpression of DJ-1 failing to restore the antioxidant capacity of Atox1 mutants. The findings suggest that DJ-1 mediates the ability of Atox1 to withstand oxidative stress. And targeting Atox1 could be a potential therapeutic approach for addressing post-traumatic neurological dysfunction.

A Narrative Review on Financial Challenges and Health Care Costs Associated with Traumatic Brain Injury in the United States

Traumatic Brain Injury (TBI) is a highly prevalent and potentially severe medical condition. Challenges regarding TBI management are related to accurate diagnostics, defining its severity and establishing prompt interventions in order to impact outcomes. Among the healthcare components in TBI handling strategy is intracranial pressure (ICP) monitoring, which is fundamental to therapy decisions. However, ICP monitoring is an Aquiles tendon, imposing a significant financial burden on healthcare systems, particularly in middle and low-income communities. This review primarily investigates the economic burden of TBI and whether new technologies are suitable to reduce its healthcare costs without compromising the quality of care, according to the levels of evidence available MATERIAL AND METHODS: For this narrative review, the authors conducted a PUBMED search for articles discussing TBI healthcare costs, as well as monitoring technologies (tomography, magnetic resonance imaging, optic nerve sheath diameter, transcranial Doppler, pupillometry and noninvasive ICP waveform) and their application in managing TBI. Strategies were first evaluated from a medical noninferiority perspective before calculating the average savings of each selected strategy. All applicable papers were analyzed for quality using the Consolidated Health Economic Evaluation Reporting Standards 2022 Statement (CHEERS 2022)117 and the paper was written to conform as much as possible with it. The review included a total of 109 references and revealed a consistent potential in noninvasive technologies to reduce costs while maintaining or improving the quality of care. TBI prevalence has grown with an unproportionate healthcare burden in the last decades. Noninvasive monitoring techniques seem to be effective to reduce TBI healthcare costs, with no neglectable limitations, especially the need for more supporting scientific evidence. The clinical and financial undeniable potential of these techniques are compelling to further investigate their role in TBI management, as well as the creation of more comprehensive monitoring models to the understanding of complex phenomena occurring in the injured brain.

Management of traumatic brain injury in Africa: Challenges and opportunities.

Traumatic brain injury (TBI) is a major public health concern globally, with significant implications for morbidity, mortality, and long-term disability. While extensive research has been conducted on TBI management in high-income countries, limited attention has been given to the specific challenges and opportunities faced by healthcare systems in Sub-Saharan Africa (SSA). This perspective study aims to provide a comprehensive overview of the current status of TBI management in SSA, focusing on the unique challenges and potential opportunities for improvement. The findings highlight several key challenges faced by SSA healthcare systems in managing TBIs, including limited resources, inadequate infrastructure, and a shortage of trained healthcare professionals. Furthermore, social and cultural factors, such as ignorance of driving laws, financial constraints, and limited access to modern technology services. However, the study also identifies potential opportunities for improving TBI management in SSA. These include strengthening healthcare infrastructure, enhancing pre-hospital care and transportation systems, and increasing public awareness and education about TBI. This perspective study emphasizes the urgent need for tailored interventions and strategies to address the unique challenges faced by SSA in managing TBIs. Addressing the challenges and opportunities in brain injury management in sub-Saharan Africa requires a comprehensive approach which can be through investing in health infrastructure, addressing socioeconomic inequalities, implementing prevention strategies, and fostering evidence-based research collaboration. Through this, the region can significantly improve TBI care and outcomes, thereby improving the well-being of people affected by TBI in sub-Saharan Africa.

Clinical Management in Traumatic Brain Injury.

Traumatic brain injury is one of the leading causes of morbidity and mortality worldwide and is one of the major public healthcare burdens in the US, with millions of patients suffering from the traumatic brain injury itself (approximately 1.6 million/year) or its repercussions (2-6 million patients with disabilities). The severity of traumatic brain injury can range from mild transient neurological dysfunction or impairment to severe profound disability that leaves patients completely non-functional. Indications for treatment differ based on the injury's severity, but one of the goals of early treatment is to prevent secondary brain injury. Hemodynamic stability, monitoring and treatment of intracranial pressure, maintenance of cerebral perfusion pressure, support of adequate oxygenation and ventilation, administration of hyperosmolar agents and/or sedatives, nutritional support, and seizure prophylaxis are the mainstays of medical treatment for severe traumatic brain injury. Surgical management options include decompressive craniectomy or cerebrospinal fluid drainage via the insertion of an external ventricular drain. Several emerging treatment modalities are being investigated, such as anti-excitotoxic agents, anti-ischemic and cerebral dysregulation agents, S100B protein, erythropoietin, endogenous neuroprotectors, anti-inflammatory agents, and stem cell and neuronal restoration agents, among others.

Neuroprotective effects of takinib on an experimental traumatic brain injury rat model via inhibition of transforming growth factor beta-activated kinase 1

Transforming growth factor β-activated kinase 1 (TAK1) plays a significant role in controlling several signaling pathways involved with regulating inflammation and apoptosis. As such, it represents an important potential target for developing treatments for traumatic brain injury (TBI). Takinib, a small molecule and selective TAK1 inhibitor, has potent anti-inflammatory activity and has shown promising activity in preclinical studies using rat models to evaluate the potential neuroprotective impact on TBI. The current study used a modified Feeney's weight-drop model to cause TBI in mature Sprague-Dawley male rats. At 30 min post-induction of TBI in the rats, they received an intracerebroventricular (ICV) injection of Takinib followed by assessment of their histopathology and behavior. The results of this study demonstrated how Takinib suppressed TBI progression in the rats by decreasing TAK1, p-TAK1, and nuclear p65 levels while upregulating IκB-α expression. Takinib was also shown to significantly inhibit the production of two pro-inflammatory factors, namely tumor necrosis factor-α and interleukin-1β. Furthermore, Takinib greatly upregulated the expression of tight junction proteins zonula occludens-1 and claudin-5, reducing cerebral edema. Additionally, Takinib effectively suppressed apoptosis via downregulation of cleaved caspase 3 and Bax and reduction of TUNEL-positive stained cell count. As a result, an enhancement of neuronal function and survival was observed post-TBI. These findings highlight the medicinal value of Takinib in the management of TBI and offer an experimental justification for further investigation of TAK1 as a potential pharmacological target.

Olfactory function after mild traumatic brain injury in children-a longitudinal case control study.

The prevalence of posttraumatic olfactory dysfunction in children after mild traumatic brain injury ranges from 3 to 58%, with potential factors influencing this variation, including traumatic brain injury severity and assessment methods. This prospective longitudinal study examines the association between mild traumatic brain injury and olfactory dysfunction in children. Seventy-five pediatric patients with mild traumatic brain injury and an age-matched healthy control group were enrolled. Olfactory function was assessed using the Sniffin' Sticks battery, which focuses on olfactory threshold and odor identification. The study found that children with mild traumatic brain injury had impaired olfactory function compared with healthy controls, particularly in olfactory threshold scores. The prevalence of olfactory dysfunction in the patient group was 33% and persisted for 1yr. No significant association was found between traumatic brain injury symptoms (e.g. amnesia, loss of consciousness) and olfactory dysfunction. The study highlights the importance of assessing olfactory function in children after mild traumatic brain injury, given its potential impact on daily life. Although most olfactory dysfunction appears transient, long-term follow-up is essential to fully understand the recovery process. The findings add valuable insights to the limited literature on this topic and urge the inclusion of olfactory assessments in the management of pediatric mild traumatic brain injury.