Brain Injury Research Articles

SP1-mediated SYN1 promotes hemin-induced damage in PC12 cells in vitro and exacerbates blood-barrier disruption and brain injury after intracerebral hemorrhage in vivo

BackgroundIntracerebral hemorrhage (ICH) is one deadly subtype of stroke with high morbidity and mortality. Oxidative stress and inflammation are major factors contributing to blood-brain barrier (BBB) dysfunction, which induces perihematoma edema and exacerbates ICH-induced secondary brain injury. SYN1 is a crucial neuronal phosphoprotein that plays a pivotal role in neuronal development. Our study was devised to clarify the function of SYN1 in hemin-induced cell injury in PC12 cells and brain injury in ICH rat models. MethodsFor in vitro assay, PC12 cells were first stimulated by 150µM hemin for 4h and then transfected with si-SYN1 and pcDNA3.1-SP1. Cell viability was tested through lactate dehydrogenase (LDH) release and CCK-8 assays. Cell apoptosis was observed through TUNEL staining. Inflammatory factors (IL-1β, IL-6, and TNF-α) were evaluated through western blotting. Oxidative markers (GSH, MDA, and SOD) were detected by adopting commercial kits. The binding sites of SP1 on the SYN1 promoter were predicted by using the JASPAR database and were validated through performing CHIP and luciferase reporter assays. SP1 and SYN1 expression in PC12 cells was investigated by RT-qPCR. For in vivo assay, rats were administrated intracerebroventricularly with si-SYN1 at 72h before ICH induction. SYN1 and SP1 expression in ICH rats was assessed by RT-qPCR. Neurological deficits, brain edema, and BBB disruption at 24h following ICH were assessed by conducting neurobehavioral tests, brain water content examination, and Evans blue extravasation assay. ResultsIn vitro, hemin stimulation elevated SYN1 expression, attenuated cell viability, enhanced apoptosis, and induced inflammation and oxidative stress in PC12 cells, which were offset by SYN1 knockdown. SP1 bound to the SYN1 promoter region and positively regulated SYN1 expression. Overexpressing SP1 antagonized the impacts of SYN1 downregulation on hemin-induced damage in PC12 cells. In vivo, SYN1 and SP1 expression was upregulated in ICH rat models. Administration of si-SYN1 effectually improved neurological function, attenuated brain edema, and ameliorated BBB disruption following ICH. ConclusionSP1-mediated SYN1 probably participates in the process of neuronal damage, BBB disruption, and brain injury following ICH.

METTL3 inhibits microglial pyroptosis in neonatal hypoxia-ischemia encephalopathy by regulating GPR39 expression in an m6A-HuR-dependent manner

BackgroundNeonatal hypoxia–ischemia encephalopathy (HIE) is a significant reason for neonatal mortality and prolonged disability. We have previously revealed that GPR39 activation attenuates neuroinflammation in a neonatal HIE rat model. This study aimed to investigate whether GPR39 affected microglial pyroptosis post-HIE. MethodsA neonatal rat model of HIE and a microglia cell model of oxygen-glucose deprivation (OGD) were established. Neuronal loss and cerebral infarction were assessed by using TTC, H&E staining, and Nissl staining. Pyroptosis was evaluated with western blot, LDH assay kit, ELISA, and flow cytometry. Total m6A level and GPR39 m6A modification were determined using m6A dot blot and MeRIP. The interaction between METTL3/HuR/GSK3β and GPR39 was analyzed by performing molecular interaction experiments. GPR39 mRNA stability was examined with actinomycin D. ResultsThe level of GPR39 was increased in neonatal HIE rats and OGD-treated microglia. Brain injury and neuronal loss were significantly increased in the HIE model when GPR39 was knocked down. GPR39 knockdown aggravated NLRP3 inflammasome-mediated microglial pyroptosis. METTL3 upregulated GPR39 expression in an m6A-dependent manner. METTL3 enhanced the interaction of HuR and GPR39. In OGD-exposed microglia, METTL3 elevated GPR39 expression and mRNA stability, which declined after HuR depletion. METTL3 knockdown promoted microglial pyroptosis, which was reversed by GPR39 agonist. Furthermore, microglial pyroptosis was inhibited by GPR39 upregulation, but the outcome was reverted by GSK3β activator SNP. ConclusionMETTL3 inhibits microglial pyroptosis in neonatal HIE via regulating m6A-HuR dependent stabilization of GPR39, which contributes to therapeutics development for neonatal HIE.

Inflammatory mediators-induced DNA damage in liver and brain injury: Therapeutic approach of 5-Methoy-N-acetyltryptamine

Inflammatory mediators-induced DNA damage in liver and brain injury: Therapeutic approach of 5-Methoy-N-acetyltryptamine

The Recovery of Consciousness via Evidence-Based Medicine and Research (RECOVER) Program: A Paradigm for Advancing Neuroprognostication.

Neuroprognostication for disorders of consciousness (DoC) after severe acute brain injury is a major challenge, and the conventional clinical approach struggles to keep pace with a rapidly evolving literature. Lacking specialization, and fragmented between providers, conventional neuroprognostication is variable, frequently incongruent with guidelines, and prone to error, contributing to avoidable mortality and morbidity. We review the limitations of the conventional approach to neuroprognostication and DoC care, and propose a paradigm entitled the Recovery of Consciousness Via Evidence-Based Medicine and Research (RECOVER) program to address them. The aim of the RECOVER program is to provide specialized, comprehensive, and longitudinal care that synthesizes interdisciplinary perspectives, provides continuity to patients and families, and improves the future of DoC care through research and education. This model, if broadly adopted, may help establish neuroprognostication as a new subspecialty that improves the care of this vulnerable patient population.

Temporal differential effects of post-injury alcohol consumption in a mouse model of blast-induced traumatic brain injury

Traumatic brain injury is a prevalent condition that affects millions worldwide with no clear understanding or effective therapeutic management available. Military soldiers have a high risk of exposure to blast-induced traumatic brain injury (bTBI). Furthermore, alcohol drinking is common in this population, and studies have shown that post-TBI alcohol exposure can result in memory loss. Hence, it is possible that alcohol could contribute to the overall pathological outcome of brain trauma. However, such a possibility has not been explored in detail. Here, we combined a mild bTBI (mbTBI) model with the drinking-in-the-dark (DID) paradigm to investigate the pathological synergy between mbTBI and alcohol consumption by examining brain oxidative stress levels and behavioral alterations in mice. The results revealed the anxiolytic and short-term memory improvement effects of post-trauma alcohol drinking examined at an early timepoint post mbTBI. However, extended alcohol drinking for up to three weeks post mbTBI impaired long-term memory and was accompanied by intensified oxidative stress in brain regions associated with memory and anxiety. These findings, as well as those from previous in vitro TBI/alcohol studies, suggest a pathological synergy of physical force and post-impact alcohol exposure. This knowledge could potentially aid in establishing guidelines for TBI victims to avoid further injury to their brains as well as to help maximize their recovery following TBI.

Head kinematics of human subjects during laboratory-induced ladder falls to the ground

Introduction: Fall-induced traumatic brain injury (TBI) is considered one of the most serious occupational injuries in construction. Given the frequency of falls from ladders, knowledge of head kinematics during ladder falls to the ground may help inform any potential improvement to construction safety helmet design and improve their protection against head injury. Therefore, the goal of this descriptive study was to measure head kinematics during laboratory-induced ladder falls to the ground. Method: Eighteen young adults wearing a hockey helmet simulated construction tasks that challenged their balance while standing on stepladders and an extension ladder with their feet at heights up to 1.8 m above padding covering the ground. Falls onto the padding occurred spontaneously or were induced by an investigator nudging the ladder to simulate ladder movement resulting from the ground shifting. Optoelectronic motion capture was used to capture head kinematics up to the instant immediately before head impact. Results: Of 115 total falls, 15 involved head impact with the padding and were analyzed. Head impact during all 15 of these falls occurred on the back of the head. Immediately before impact with the padding, head vertical velocity ranged from 0.42 to 3.88 m/s and head angular velocity about a medial–lateral axis ranged from 60.1 to 1215.5 deg/s. Conclusions: These data can be used with computer simulations or headform impact testing to estimate true head impact kinematics, or to inform future versions of construction safety helmet testing standards. Practical applications: This is the first study we are aware of to capture head kinematics of human subjects during ladder falls to the ground. These results have the potential to inform future versions of construction safety helmet testing standards and contribute to improved helmet design for protection against fall-induced head injury.

Emerging Neuroprotective Strategies: Unraveling the Potential of HDAC Inhibitors in Traumatic Brain Injury Management.

Traumatic brain injury (TBI) is a significant global health problem, leading to high rates of mortality and disability. It occurs when an external force damages the brain, causing immediate harm and triggering further pathological processes that exacerbate the condition. Despite its widespread impact, the underlying mechanisms of TBI remain poorly understood, and there are no specific pharmacological treatments available. This creates an urgent need for new, effective neuroprotective drugs and strategies tailored to the diverse needs of TBI patients. In the realm of gene expression regulation, chromatin acetylation plays a pivotal role. This process is controlled by two classes of enzymes: histone acetyltransferase (HAT) and histone deacetylase (HDAC). These enzymes modify lysine residues on histone proteins, thereby determining the acetylation status of chromatin. HDACs, in particular, are involved in the epigenetic regulation of gene expression in TBI. Recent research has highlighted the potential of HDAC inhibitors (HDACIs) as promising neuroprotective agents. These compounds have shown encouraging results in animal models of various neurodegenerative diseases. HDACIs offer multiple avenues for TBI management: they mitigate the neuroinflammatory response, alleviate oxidative stress, inhibit neuronal apoptosis, and promote neurogenesis and axonal regeneration. Additionally, they reduce glial activation, which is associated with TBI-induced neuroinflammation. This review aims to provide a comprehensive overview of the roles and mechanisms of HDACs in TBI and to evaluate the therapeutic potential of HDACIs. By summarizing current knowledge and emphasizing the neuroregenerative capabilities of HDACIs, this review seeks to advance TBI management and contribute to the development of targeted treatments.

Pharmacokinetics and brain uptake of sodium selenate and selenium in naïve rats and a lateral fluid percussion injury ratmodel.

Post-traumatic epilepsy (PTE) is a life-long complication of traumatic brain injury (TBI). The development of PTE is associated with neurological morbidity and increases the risk of mortality. An aim of EpiBioS4Rx (Epilepsy Bioinformatics Study for Antiepileptogenic Therapy) was to test potential therapies to prevent the development of PTE in the lateral fluid percussion injury (LFPI) rat model of TBI, in which rats were subjected to injury at the left parietal cortex. Sodium selenate has been reported to be antiepileptogenic post-TBI in rodent models by activating protein phosphatase 2A and reducing phosphorylated tau (p-tau) protein. We aimed to characterize the pharmacokinetics (PK) and brain uptake of sodium selenate using naïve control and LFPI rats. Rats received either a single bolus dose or a single bolus dose followed by a 7-day subcutaneous minipump infusion of sodium selenate. Sodium selenate and selenium concentrations in plasma and brain were analyzed and used for PK estimation and brain exposure assessment. Selenium concentrations rapidly increased after sodium selenate administration, demonstrating biotransformation from sodium selenate to selenium. Sodium selenate and selenium PK parameters were estimated using non-compartmental analysis. Sodium selenate clearance (CL/F) and volume of distribution (Vd/F) varied by dose and route of administration, suggesting differences in bioavailability and nonlinear pharmacokinetics at the doses tested. Brain-to-plasma partition coefficients (AUCbrain/AUCplasma) for sodium selenate and selenium were found to be 0.7-1.3 and 0.1-0.3 following single-dose injection, respectively, indicating active transport of sodium selenate across the blood-brain barrier (BBB).

Basal forebrain-lateral habenula inputs and control of impulsive behavior.

Deficits in impulse control are observed in several neurocognitive disorders, including attention deficit hyperactivity (ADHD), substance use disorders (SUDs), and those following traumatic brain injury (TBI). Understanding brain circuits and mechanisms contributing to impulsive behavior may aid in identifying therapeutic interventions. We previously reported that intact lateral habenula (LHb) function is necessary to limit impulsivity defined by impaired response inhibition in rats. Here, we examine the involvement of a synaptic input to the LHb on response inhibition using cellular, circuit, and behavioral approaches. Retrograde fluorogold tracing identified basal forebrain (BF) inputs to LHb, primarily arising from ventral pallidum and nucleus accumbens shell (VP/NAcs). Glutamic acid decarboxylase and cannabinoid CB1 receptor (CB1R) mRNAs colocalized with fluorogold, suggesting a cannabinoid modulated GABAergic pathway. Optogenetic activation of these axons strongly inhibited LHb neuron action potentials and GABA release was tonically suppressed by an endogenous cannabinoid in vitro. Behavioral experiments showed that response inhibition during signaled reward omission was impaired when VP/NAcs inputs to LHb were optogenetically stimulated, whereas inhibition of this pathway did not alter LHb control of impulsivity. Systemic injection with the psychotropic phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC), also increased impulsivity in male, and not female rats, and this was blocked by LHb CB1R antagonism. However, as optogenetic VP/NAcs pathway inhibition did not alter impulse control, we conclude that the pro-impulsive effects of Δ9-THC likely do not occur via inhibition of this afferent. These results identify an inhibitory LHb afferent that is controlled by CB1Rs that can regulate impulsive behavior.

Brain endothelial cell activation and dysfunction associate with and contribute to the development of enlarged perivascular spaces and cerebral small vessel disease.

Multiple injurious stimuli to the brain's endothelium results in brain endothelial cell activation and dysfunction (BECact/dys) with upregulation of inflammatory signaling cascades and a decrease in bioavailable nitric oxide respectively. These injurious stimuli initiate a brain injury and a response to injury wound healing genetically programed cascade of events, which result in cellular remodeling of the neurovascular unit and blood-brain barrier with increased inflammation and permeability. These remodeling changes also include the perivascular spaces that become dilated to form enlarged perivascular spaces (EPVS) that may be identified noninvasively by magnetic resonance imaging. These EPVS are associated with and considered to be a biomarker for cerebral small vessel disease (SVD) and a dysfunctional glymphatic system with impaired removal of neurotoxic waste, which ultimately results in neurodegeneration with impaired cognition and dementia. The penultimate section discusses the understudied role of venous cerebral circulation in relation to EPVS, SVD, and the vascular contribution to cognitive impairment (VCID). The focus of this review will be primarily on BECact/dys that associates with and contributes to the development of EPVS, SVD, and impaired glymphatic system efflux. Importantly, BECact/dys may be a key piece of the puzzle to unlock this complicated story of EPVS and SVD. Multiple transmission electron micrographs and illustrations will be utilized to depict anatomical ultrastructure and allow for the discussion of multiple functional molecular cascades.

New Insights on Mechanisms and Therapeutic Targets of Cerebral Edema.

Cerebral Edema (CE) is the final common pathway of brain death. In severe neurological disease, neuronal cell damage first contributes to tissue edema, and then Increased Intracranial Pressure (ICP) occurs, which results in diminishing cerebral perfusion pressure. In turn, anoxic brain injury brought on by decreased cerebral perfusion pressure eventually results in neuronal cell impairment, creating a vicious cycle. Traditionally, CE is understood to be tightly linked to elevated ICP, which ultimately generates cerebral hernia and is therefore regarded as a risk factor for mortality. Intracranial hypertension and brain edema are two serious neurological disorders that are commonly treated with mannitol. However, mannitol usage should be monitored since inappropriate utilization of the substance could conversely have negative effects on CE patients. CE is thought to be related to bloodbrain barrier dysfunction. Nonetheless, a fluid clearance mechanism called the glial-lymphatic or glymphatic system was updated. This pathway facilitates the transport of cerebrospinal fluid (CSF) into the brain along arterial perivascular spaces and later into the brain interstitium. After removing solutes from the neuropil into meningeal and cervical lymphatic drainage arteries, the route then directs flows into the venous perivascular and perineuronal regions. Remarkably, the dual function of the glymphatic system was observed to protect the brain from further exacerbated damage. From our point of view, future studies ought to concentrate on the management of CE based on numerous targets of the updated glymphatic system. Further clinical trials are encouraged to apply these agents to the clinic as soon as possible.

Exploring Neuroprotection against Radiation-Induced Brain Injury: A Review of Key Compounds.

Brain radiation is a crucial tool in neuro-oncology for enhancing local tumor control, but it can lead to mild-to-profound and progressive impairments in cognitive function. Radiation-induced brain injury is a significant adverse effect of radiotherapy for cranioencephalic tumors, primarily caused by indirect cellular damage through the formation of free radicals. This results in late neurotoxicity manifesting as cognitive impairment due to free radical production. The aim of this review is to highlight the role of different substances, such as drugs used in the clinical setting and antioxidants such as ascorbate, in reducing the neurotoxicity associated with radiation-induced brain injury. Currently, there is mainly preclinical and clinical evidence supporting the benefit of these interventions, representing a cost-effective and straightforward neuroprotective strategy.

Design and methodology of a randomized clinical trial of quetiapine to reduce central nervous system polypharmacy in veterans with postconcussive syndrome symptoms

Lack of evidence to guide medication treatments for mild traumatic brain injury (mTBI) in veterans too often results in polypharmacy practices attempting to provide symptomatic relief from multiple postconcussive syndrome symptoms. Therefore, the field needs to find an effective medication that reduces the burden of postconcussive symptoms without complicating the treatment burden of veterans. This clinical trial seeks to determine whether switching veterans to quetiapine monotherapy (intervention) is superior to continuing to receive treatment as usual (TAU, control) polypharmacy for veterans with symptoms of postconcussive syndrome and posttraumatic stress disorder who are receiving rehabilitation treatment for mTBI. This study will test the conceptual mediation model hypothesis that quetiapine monotherapy may enhance recovery from mTBI by (1) increasing engagement in rehabilitation services, and/or (2) reducing the adverse effects of TAU polypharmacy. This study will enroll 146 patients from two Veterans Administration Medical Centers into a 12- week phase III, randomized, pragmatic clinical trial comparing outcomes from treatment with quetiapine monotherapy and TAU. Quetiapine will be cross tapered up to a maximum dose of 200 mg (as tolerated) as other medications are discontinued. The primary outcome measures are postconcussive syndrome symptoms (Neurobehavioral Symptom Inventory), functional disability (World Health Organization Disability Assessment), and quality of life (World Health Organization Quality of Life Assessment). Overall, this study aims to determine whether quetiapine monotherapy is superior to TAU polypharmacy and improves the quality of life for veterans with comorbid postconcussive syndrome and posttraumatic stress disorder symptoms who are receiving rehabilitation treatment for mTBI.

Transient cerebral ischaemia alters mesenteric arteries in hypertensive rats: Limited reversal despite suberoylanilide hydroxamic acid cerebroprotection.

Stroke induces brain injury, especially severe in hypertensive patients, and elevates mortality rates through non-neurological complications. However, the potential effects of a transient ischaemic episode on the peripheral vasculature of hypertensive individuals remain unclear. We investigated whether transient cerebral ischaemia (90 min)/reperfusion (1 or 8 days) induces alterations in mesenteric resistance artery (MRA) properties in adult male spontaneously hypertensive rats (SHR). In addition, we assessed whether the reported cerebroprotective effects of suberoylanilide hydroxamic acid (SAHA; 50 mg/kg; administered intraperitoneally at 1, 4, or 6 h after reperfusion onset) extend over several days and include beneficial effects on MRAs. Functional and structural properties of MRAs were examined at 1- and 8-days post-stroke. Nuclei distribution, collagen content, and oxidative stress were assessed. Ischaemic brain damage was evaluated longitudinally using magnetic resonance imaging. Following stroke, MRAs from SHR exhibited non-reversible impaired contractile responses to the thromboxane A2 receptor agonist U46619. Stroke increased the MRA cross-sectional area, wall thickness, and wall/lm ratio due to augmented collagen deposition. These changes were partially sustained 8 days later. SAHA did not improve U46619-induced contractions but mitigated stroke-induced oxidative stress and collagen deposition, preventing MRA remodelling at 24 h of reperfusion. Furthermore, SAHA induced sustained cerebroprotective effects over 8 days, including reduced brain infarct and oedema, and improved neurological scores. However, SAHA had minimal impact on chronic MRA contractile impairments and remodelling. These findings suggest that stroke causes MRA changes in hypertensive subjects. While SAHA treatment offers sustained protection against brain damage, it cannot fully restore MRA alterations.

Effects of major trauma care organisation on mortality in a European level 1 trauma centre: A retrospective analysis of 2016-2023.

The centralisation of care for trauma patients in trauma centres, alongside the creation of inclusive trauma networks, has proven to reduce mortality. In Europe, such structured trauma programs and trauma networks are in development. To describe the aetiology and evolution of in-hospital mortality in a developing European level 1 trauma centre, to determine the early effect of trauma care reorganisation on mortality and to identify the areas for future investments in trauma care. This retrospective analysis included the calculation of the standardised mortality ratio (SMR), the time to in-hospital death and the cause of in-hospital death of all primary major trauma admissions to the Antwerp University Hospital from 2016 to 2023. A total of 1470 patients was included with a crude mortality of 16.4 %, a median Revised Injury Severity Classification II (RISC II) adjusted mortality of 1.47 %, and a SMR of 1.12. A limitation of care directive was registered for 18.1 % of the patients. The causes of in-hospital death were traumatic brain injury (TBI) in 60 %, haemorrhagic shock in 15 %, organ failure in 10 %, miscellaneous in 14 % and unknown in 1 %. Sixty percent died in the first 48 h of hospital admission (mainly due to TBI and haemorrhagic shock) and 27 % died after more than seven days (mainly due to organ failure and TBI). In 24 % of the deceased patients with severe TBI, a non-TBI related cause of death was found. Overall, the SMR showed a nonsignificant decreasing trend, with a significant decrease of the SMR in the highest risk group (RISCII > 75 %) and a nonsignificant increase in the lowest risk group (RISC II <15 %). The standardised mortality ratio declined over a period of 8 years, even though the SMR increased nonsignificantly in the lowest risk-adjusted mortality group. Future analysis of this subgroup could clarify whether this trend is due to an increase of limitation of care directives and if these deaths could have been prevented with improved trauma care. There might be opportunities to increase the survival of patients with severe TBI who have a non-TBI cause of death.

Assessment of traumatic brain injury treatment guided by continuous monitoring of intracranial pressure and brain tissue oxygen partial pressure: A single-center pilot study

Severe traumatic brain injury (TBI) is a leading cause of death and disability. Monitoring intracranial pressure (ICP) is recommended, but the data on the outcomes are conflicting. Adding continuous brain tissue oxygen partial pressure (PbtO2) monitoring may have some benefit but the OXY-TC suggested it did not improve 6-month neurological outcomes. This single-center pilot randomized controlled study aimed to evaluate whether adding PbtO2 monitoring was feasible and could improve the prognosis of severe TBI. The participants were randomized into either an ICP alone or an ICP + PbtO2 group for 7 days, with treatment protocols based on existing guidelines. Clinical parameters were collected hourly. The primary outcome was the feasibility of using PbtO2 monitoring. The secondary outcomes were 6-month survival, analyzed by the log-rank test, the 3- and 6-month Glasgow Outcome Scale (GOS) scores, compared between groups by chi-squared test. Seventy patients were included (36 ICP, 34 ICP + PbtO2). The ICP + PbtO2 group had lower mean daily ICP (13.4 vs. 18.2 mmHg, P = 0.0024) and higher mean daily cerebral perfusion pressure (82.1 vs. 74.5 mmHg, P = 0.0055). The ICP + PbtO2 group had higher 6-month survival (79.4 % vs. 55.6 %, P = 0.0337) and more favorable outcomes at 3 months (67.6 % vs. 38.9 %, P = 0.0160) and 6 months (70.6 % vs. 41.7 %, P = 0.0149). Adding PbtO2 monitoring to ICP monitoring is feasible in patients with severe TBI and could maybe improve the intermediate-term outcomes. The results will serve to design larger trials.

Bioactive hydrogel synergizes neuroprotection, macrophage polarization, and angiogenesis to improve repair of traumatic brain injury

Traumatic brain injury (TBI) can lead to severe neurotrauma, leading to long-term cognitive decline and even death. Massive neuronal loss and excessive neuroinflammation are critical issues in the treatment of secondary TBI. To tackle these challenges, we developed a GelMA and CSMA hydrogel loaded with Erythropoietin (EPO) and Interleukin-4 (IL-4), named GC/I/E. By directly loading the hydrogel with EPO, rapid neuroprotection and angiogenesis were achieved. Meanwhile, by loading Mesoporous silica nanoparticles (MSNs) with IL-4 (MSN@IL-4), sustained inflammation modulation during inflammation was attained. In vitro experiments demonstrated that GC/I/E hydrogel were biocompatible and could provide neuroprotection for HT22 cells in H2O2 environment, regulate RAW264.7 polarization from M1 to M2 phenotype and promote HUVEC angiogenesis. In vivo experiments demonstrated that GC/I/E hydrogel reduced brain oedema and Nissl body damage, inhibited inflammatory expression of G3-FFAP and neural scarring, improved microvascular and vascular function reconstruction, and facilitated neuronal and synaptogenesis, ultimately improving neurofunctional recovery in TBI. RNA sequencing results demonstrated that GC/I/E hydrogel treatment significantly correlated with the regulation of genes such as apoptosis, inflammation regulation, and neural regeneration. This bioactive hydrogel with neuroprotection, inflammation modulation and promotion of angiogenesis has great potential for TBI treatment.

Neuro-regeneration or Repair: Cell Therapy of Neurological Disorders as A Way Forward.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.

Epilepsy in children and anesthesia

Epilepsy, also called seizure disorder, is the most common childhood brain disorder in the United States. The aetiology of epilepsy in children is multifactorial with congenital, metabolic, infective, and problems associated with prematurity being common causes. Nearly 3 million Americans have epilepsy. About 450,000 of them are under 17 years old. About 1 in 200 children (0.5%) have epilepsy, a neurological condition where children have a predisposition to recurrent, unprovoked seizures. There are many different types of epilepsy, especially in infancy, childhood and adolescence. Epilepsy can be thought of in terms of either: the site of seizure origin in the brain (generalised or focal seizures), or the underlying cause. Genetic epilepsies (formerly called idiopathic or primary epilepsies) occur in an otherwise normal person and are due to a genetic predisposition to seizures. Some epilepsies are due to an underlying abnormality of the brain structure or chemistry (formerly called symptomatic or secondary epilepsies). Other epilepsies have no known cause. Epilepsy is commonly diagnosed in children and can be confused with other conditions. An accurate diagnosis is essential. A seizure is an excessive surge of electrical activity in the brain that can cause a variety of symptoms, depending on which parts of the brain are involved. Seizures can be provoked or unprovoked. Provoked seizures, caused by fever in a young child or severe hypoglycemia, are not considered to be forms of epilepsy. Unprovoked seizures have no clear cause but can be related to genetics or brain injury. When a child has two or more unprovoked seizures, epilepsy is often the diagnosis. Despite advances in antiepileptic medication therapy, a significant number of pediatric patients with epilepsy have seizures that are not well controlled. Antiepileptic medications interact with anesthetic agents, and common anesthetics can precipitate or suppress seizure activity. There are important pharmacokinetic and pharmacodynamic interactions between AEDs and drugs commonly used in anaesthesia. These affect both drug efficacy and the risk of seizure activity intraoperatively.

Racial and Socioeconomic Disparities in Traumatic Brain Injury Outcomes: Insights From a Nationwide Analysis

BACKGROUND AND OBJECTIVES: To examine the effects of racial and socioeconomic disparities on clinical outcomes: in-hospital mortality, discharge dispositions, and hospital length of stay (LOS) among patients with traumatic brain injury (TBI) stratified by race and socioeconomic status (SES). METHODS: We conducted a retrospective analysis by analyzing the 1995-2015 Nationwide Inpatient Sample database. Adjusted logistic regressions and multinomial logistic regression models with and without propensity score matching were applied to investigate the effects of disparities on clinical outcomes. RESULTS: African American and Hispanic patients with TBI had a lower risk of in-hospital mortality, longer hospital LOS, and lower likelihood of being discharged to rehabilitation compared with White patients. The TBI patients with poor SES (pSES) had lower in-hospital mortality and were more likely to leave against medical advice compared with non-pSES TBI patients. CONCLUSION: Racial and socioeconomic disparities had significant influences on in-hospital mortality, discharge dispositions, and hospital LOS among the TBI population. Our study observed pSES TBI patients had a lower likelihood of in-hospital mortality than non-pSES patients, which may be partially attributed to the fact that most of the pSES TBI patients were hospitalized in urban teaching hospitals and hospitals with large bed size. In effect, our data suggest that the Social Safety Net of the United States is effective in preventing mortality in patients with TBI.