Introduction: Traumatic Brain Injury (TBI) is a major public health problem causing significant morbidity and mortality in young adults. This study aimed to describe the epidemiological, diagnostic, therapeutic, and e...Introduction: Traumatic Brain Injury (TBI) is a major public health problem causing significant morbidity and mortality in young adults. This study aimed to describe the epidemiological, diagnostic, therapeutic, and evolutionary aspects of TBI. Materials and Methods: This was a prospective, descriptive study conducted from 1 April 2022 to 31 March 2023 on patients admitted to and treated for cranioencephalic trauma in the General Surgery department of Kara Regional Hospital. Results: Eighty-three (83) patients with cranioencephalic trauma were managed out of 773 patients admitted to the department during the study period. The mean age was 34 ± 14.98 years and the sex ratio was 3.6 in favour of men. Motorbike taxi drivers were the social group most affected (n = 33, 40%). The causes of trauma were dominated by public road accidents (n = 80;96%). TBI was mild (n = 40;48%), moderate (n = 35;42%) and severe (n = 8;10%). Cerebral CT scans were performed in 19 patients (23%). Cerebral contusion (n = 4) was the most frequent cerebral lesion. Six patients (7%) with severe head injuries were transferred to Kara University Hospital. Six deaths (7%) occurred in patients with severe head injuries. The main sequelae were intermittent headaches in all patients reviewed, and memory problems (6%). Conclusion: Traumatic brain injuries are common at Kara Regional Hospital. Severe cranial trauma is less frequent but leads to death because of financial difficulties and limited technical facilities.展开更多
Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechani...Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.展开更多
Target of research in subarachnoid hemorrhage(SAH):The outcome of aneurysmal SAH remains poor despite advances in the diagnosis and treatment.Although many factors related to patients,aneurysms,and institutions,as wel...Target of research in subarachnoid hemorrhage(SAH):The outcome of aneurysmal SAH remains poor despite advances in the diagnosis and treatment.Although many factors related to patients,aneurysms,and institutions,as well as physiological parameters and medical complications were reported as prognostic factors,the most important determinant of poor展开更多
Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage(SAH), and Toll-like receptor(TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 ...Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage(SAH), and Toll-like receptor(TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor(NF)-κΒ signaling among TLR4 signaling pathways as to the development of early brain injury(EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κΒ and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.展开更多
Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily us...Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.展开更多
Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage.Secondary damage presents the greatest...Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage.Secondary damage presents the greatest challenge for medical staff;however,there are currently few effective therapeutic targets for secondary damage.Homer proteins are postsynaptic scaffolding proteins that have been implicated in ischemic and traumatic insults to the central nervous system.Homer signaling can exert either positive or negative effects during such insults,depending on the specific subtype of Homer protein.Homer 1b/c couples with other proteins to form postsynaptic densities,which form the basis of synaptic transmission,while Homer 1a expression can be induced by harmful external factors.Homer 1c is used as a unique biomarker to reveal alterations in synaptic connectivity before and during the early stages of apoptosis in retinal ganglion cells,mediated or affected by extracellular or intracellular signaling or cytoskeletal processes.This review summarizes the structural features,related signaling pathways,and diverse roles of Homer proteins in physiological and pathological processes.Upregulating Homer 1a or downregulating Homer 1b/c may play a neuroprotective role in secondary brain injuries.Homer also plays an important role in the formation of photoreceptor synapses.These findings confirm the neuroprotective effects of Homer,and support the future design of therapeutic drug targets or gene therapies for ischemic and traumatic brain injuries and retinal disorders based on Homer proteins.展开更多
Objective:To analyze characters of magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) in the diagnosis of mild trauma brain injuries(MTBI) in frontal lobe and to compare with conventional magnetic ...Objective:To analyze characters of magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) in the diagnosis of mild trauma brain injuries(MTBI) in frontal lobe and to compare with conventional magnetic resonance imaging(MRI).Methods:A total of 21 patients were selected,who all aged 12-51 years old and had injury within 24 hours.Computer tomography (CT) and the Glasgow Coma Scale were used to evaluate the degree of injury.All patients were diagnosed as MTBI,and 19 had conventional MRI,MRS and DTI.The major parameters of MRS were Probe-P sequence,TE= 144 or 35 ms,and both single voxel spectrum and chemical shift imging were included.The major parameters of DTI were diffusion directions =15,b value = 1000 s/mm^2. Frational anisotropic(FA) map and average ADC map were obtained to evaluate DTI result. Positive deletion ratio was observed and the imaging changes were compared between injured side and normal side.Results:All 21 patients had CT scan and Glasgow scale.A total of 19 patients had conventional MRI.DTI and MRS.Results of CT and conventional MRI showed no significant abnormality in lobe,and Glasgow scale showed mild type.MRS result showed significant decrease in N-acetyl aspartate(NAA) and NAA/creatine(Cr) in 13 cases(68.4%) (P【0.001),and increase in lactic acid(Lac) in 7 cases(36.8%).FA mapping of the frontal lobe displayed significant changes in 7 cases(36.8%),with 5 out of the 7 cases having increase in FA value.And there was no significant difference in average ADC.Conclusions:MRS and DTI might be more sensible than other methods,such as CT and conventional MRI in diagnosis of MTBI.The particular changes were reduced NAA and increased Lac for MRS.and increased FA values for DTI.展开更多
A new proposal for spinal cord and brain treatment and protection due to injuries and diseases is made herein. It is composed of two 20G nylon catheters with 6 lateral holes arranged circumferentially within 3 cm from...A new proposal for spinal cord and brain treatment and protection due to injuries and diseases is made herein. It is composed of two 20G nylon catheters with 6 lateral holes arranged circumferentially within 3 cm from the tip and a closed end. One catheter is inserted into the epidural space and the other catheter is inserted into the spinal space in two different lumbar interspaces using an 18G Tuohy needle 90 mm. The epidural catheter is used for cooled saline injection and infusion. The spinal catheter is used for Intralipid spinal injections and CSF aspiration. The proposal is based on the current studies on spinal cord cooling and CSF aspiration as well as on the Intralipid resuscitation properties and lipid brain protection. A study is needed to evaluate the clinical value of this combined approach.展开更多
Purpose: The aim of this study was to measure social participation in children with traumatic brain injuries (TBI) on their parental perceptions, retrospectively for the pre-injury period, at the beginning of rehabili...Purpose: The aim of this study was to measure social participation in children with traumatic brain injuries (TBI) on their parental perceptions, retrospectively for the pre-injury period, at the beginning of rehabilitation and one year after return to school. Methods: This study was conducted among 17 children aged 5 to 17 years old with moderate or severe TBI and their parents. Social participation was assessed using the LIFE-H for Children (1.0). Results: A significant decrease (p ≤ 0.001) in the level of accomplishment of life habits was found for all categories between the measurements taken pre-injury and at the beginning of rehabilitation. Significant differences (p ≤ 0.002) related to the increase in the life habit accomplishment scores were also found between measurements taken at the beginning of rehabilitation and one year after return to school. Conclusion: TBI significantly affected the accomplishment of life habits of the participants compared to their pre-injury level. The assessment of social participation at various times provides a report on the client’s progress and allows clinicians to update his or her intervention plan, to plan follow-ups or to end the intervention. This knowledge must be considered by anyone involved in helping these children to achieve their greatest social participation.展开更多
Introduction: Traumatic brain injury (TBI) in children is a common cause of emergency department admission to our institution. TBI constitutes a real public health problem in developed countries and marked increase in...Introduction: Traumatic brain injury (TBI) in children is a common cause of emergency department admission to our institution. TBI constitutes a real public health problem in developed countries and marked increase in underdeveloped countries. The aim of this study was to evaluate the results of neurosurgical treatment of TBI in children at the neurosurgery department of Yopougon Teaching Hospital, while underlining the difficulties of the adequate management of this affection in Abidjan. Patients and Methods: It was a retrospective, descriptive monocentric study performed in the neurosurgery department, of Yopougon Teaching Hospital-Abidjan (Ivory Coast) from January 2000 to December 2017. We included all patients less than 16 years old admitted to the emergency department and all admitted in neurosurgery department for a TBI with a cerebral tomodensitometry and/or a magnetic resonance imaging having undergone a neurosurgical treatment. Results: During the study period 2825 cases of TBI in children aged less than 16 years old admitted to pediatric emergencies of our institution;among them 1020 (36%) presented clinical abnormalities and/or imaging. 292 (10.34%) children were hospitalized in neurosurgery department. 108 (36.9%) had surgical treatment. The mean age of patients was 7.8 ± 0.80 years with a male predominance (64%). Of the 108 children who had been operated on, 41 had acute extra-dural hematoma evacuation, 22 had a cranio-cerebral wound healing, 36 had a lift from a fracture depressing the skull and 9 had an acute subdural hematoma evacuation with a decompressive flap. The mean delay between diagnosis and surgical care was 104 ± 67.25 hours. The postoperative evolution at the last follow-up was favorable in 96 (88.8%) children with sequelae in 12 children (6 language disorders, 2 epileptic seizures and 4 motor deficits). The postoperative mortality rate was 11.2%. Conclusion: Ivory Coast Health System does not provide optimal care management of patients with TBI. There is an emerging imperative to develop an insurance system for the management of TBI.展开更多
There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone(SVZ). However, a comprehensive understanding of SVZ cell responses to brain injuries...There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone(SVZ). However, a comprehensive understanding of SVZ cell responses to brain injuries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed flow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how flow cytometric analyses also have begun to reveal how specific cytokines, such as Leukemia inhibitory factor are coordinating SVZ responses to injury.展开更多
To discuss the treatment of spine or spinal cord injuries combined with severe traumatic brain injuries and measures to decrease invalidity and mortality rate.Methods Forty-five cases with spine or spinal cord injurie...To discuss the treatment of spine or spinal cord injuries combined with severe traumatic brain injuries and measures to decrease invalidity and mortality rate.Methods Forty-five cases with spine or spinal cord injuries combined with severe traumatic brain injuries were analyzed retrospectively.Results Among all the cases,26 were cured,14 were improved,5 died.Conclusion Early examination,early diagnosis and effective treatment are very improtant.Routine head CT plain scan and spine X-ray photographs are needed and 3 dimension CT check or MRI should also be taken if necessary.It has clinical significance to improve earlier period diagnosis rate and to decrease invalidity and mortality rate.5 refs,4 figs.展开更多
Purpose:Despite advances in modern medicine,traumatic brain injuries(TBIs)are still a major medical problem.Early diagnosis of TBI is crucial for clinical decision-making and prognosis.This study aims to compare the p...Purpose:Despite advances in modern medicine,traumatic brain injuries(TBIs)are still a major medical problem.Early diagnosis of TBI is crucial for clinical decision-making and prognosis.This study aims to compare the predictive value of Helsinki,Rotterdam,and Stockholm CT scores in predicting the 6-month outcomes in blunt TBI patients.Methods:This cohort study was conducted on blunt TBI patients of 15 years or older.All of them were admitted to the surgical emergency department of Shahid Beheshti Hospital in Kashan,Iran from 2020 to 2021 and had abnormal trauma-related findings on brain CT images.The patients’demographic data such as age,gender,history of comorbid conditions,mechanism of trauma,Glasgow coma scale,CT images,length of hospital stay,and surgical procedures were recorded.The Helsinki,Rotterdam,and Stockholm CT scores were simultaneously determined according to the existing guidelines.The included patients'6-month outcome was determined using the Glasgow outcome scale extended.M Data were analyzed by SPSS software version 16.0.Sensitivity,specificity,negative/positive predictive value and the area under the receiver operating characteristic curve were calculated for each test.The Kappa agreement coefficient and Kuder Richardson-20 were used to compare the scoring systems.Results:Altogether 171 TBI patients met the inclusion and exclusion criteria,with the mean age of(44.9±20.2)years.Most patients were male(80.7%),had traffic related injuries(83.1%)and mild TBIs(64.3%).Patients with lower Glasgow coma scale had higher Helsinki,Rotterdam,and Stockholm CT scores and lower Glasgow outcome scale extended scores.Among all the scoring systems,the Helsinki and Stockholm scores showed the highest agreement in predicting patients’outcomes(kappa=0.657,p<0.001).The Rotterdam scoring system had the highest sensitivity(90.1%)in predicting death of TBI patients,whereas the Helsinki scoring system had the highest sensitivity(89.8%)in predicting the 6-month outcome in TBI patients.Conclusion:The Rotterdam scoring system was superior in predicting death in TBI patients,whereas the Helsinki scoring system was more sensitive in predicting the 6-month outcome.展开更多
A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researche...A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.展开更多
Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely u...Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.展开更多
Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined th...Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.展开更多
Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative...Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.展开更多
Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injur...Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.展开更多
There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult p...There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.展开更多
Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. ...Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.展开更多
文摘Introduction: Traumatic Brain Injury (TBI) is a major public health problem causing significant morbidity and mortality in young adults. This study aimed to describe the epidemiological, diagnostic, therapeutic, and evolutionary aspects of TBI. Materials and Methods: This was a prospective, descriptive study conducted from 1 April 2022 to 31 March 2023 on patients admitted to and treated for cranioencephalic trauma in the General Surgery department of Kara Regional Hospital. Results: Eighty-three (83) patients with cranioencephalic trauma were managed out of 773 patients admitted to the department during the study period. The mean age was 34 ± 14.98 years and the sex ratio was 3.6 in favour of men. Motorbike taxi drivers were the social group most affected (n = 33, 40%). The causes of trauma were dominated by public road accidents (n = 80;96%). TBI was mild (n = 40;48%), moderate (n = 35;42%) and severe (n = 8;10%). Cerebral CT scans were performed in 19 patients (23%). Cerebral contusion (n = 4) was the most frequent cerebral lesion. Six patients (7%) with severe head injuries were transferred to Kara University Hospital. Six deaths (7%) occurred in patients with severe head injuries. The main sequelae were intermittent headaches in all patients reviewed, and memory problems (6%). Conclusion: Traumatic brain injuries are common at Kara Regional Hospital. Severe cranial trauma is less frequent but leads to death because of financial difficulties and limited technical facilities.
基金supported by grants R01 GM112696 and 1R35GM148177 from the National Institutes of Health(to XB)Advancing a Healthier Wisconsin(to XB)Medical College of Wisconsin-Neuroscience Research Center-Alzheimer’s Award(to XB).
文摘Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.
基金supported by a Grant-in-Aid for Scientific Research from Mie Medical Research Foundation to HS
文摘Target of research in subarachnoid hemorrhage(SAH):The outcome of aneurysmal SAH remains poor despite advances in the diagnosis and treatment.Although many factors related to patients,aneurysms,and institutions,as well as physiological parameters and medical complications were reported as prognostic factors,the most important determinant of poor
基金supported by a Grant-in-Aid for Scientific Research from Mie Medical Research Foundation to Dr.Suzuki
文摘Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage(SAH), and Toll-like receptor(TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor(NF)-κΒ signaling among TLR4 signaling pathways as to the development of early brain injury(EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κΒ and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.
基金supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+6 种基金Lundbeck Foundation Grant(R190-2014-2827)Carlsberg Foundation Grant(CF16-0663)to G.J.Z.Science and Technology Program of Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Project in Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G
文摘Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
基金supported by the National Natural Science Foundation of China,Nos.81600738(to FF),81771239(to ZF),81801300(to NS)。
文摘Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage.Secondary damage presents the greatest challenge for medical staff;however,there are currently few effective therapeutic targets for secondary damage.Homer proteins are postsynaptic scaffolding proteins that have been implicated in ischemic and traumatic insults to the central nervous system.Homer signaling can exert either positive or negative effects during such insults,depending on the specific subtype of Homer protein.Homer 1b/c couples with other proteins to form postsynaptic densities,which form the basis of synaptic transmission,while Homer 1a expression can be induced by harmful external factors.Homer 1c is used as a unique biomarker to reveal alterations in synaptic connectivity before and during the early stages of apoptosis in retinal ganglion cells,mediated or affected by extracellular or intracellular signaling or cytoskeletal processes.This review summarizes the structural features,related signaling pathways,and diverse roles of Homer proteins in physiological and pathological processes.Upregulating Homer 1a or downregulating Homer 1b/c may play a neuroprotective role in secondary brain injuries.Homer also plays an important role in the formation of photoreceptor synapses.These findings confirm the neuroprotective effects of Homer,and support the future design of therapeutic drug targets or gene therapies for ischemic and traumatic brain injuries and retinal disorders based on Homer proteins.
基金supported by the Science Foundation of Haikou Ilealth Bureau(2010-SWY-13-058)Haikou Science Technology Information Bureu(2009-049-1)
文摘Objective:To analyze characters of magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) in the diagnosis of mild trauma brain injuries(MTBI) in frontal lobe and to compare with conventional magnetic resonance imaging(MRI).Methods:A total of 21 patients were selected,who all aged 12-51 years old and had injury within 24 hours.Computer tomography (CT) and the Glasgow Coma Scale were used to evaluate the degree of injury.All patients were diagnosed as MTBI,and 19 had conventional MRI,MRS and DTI.The major parameters of MRS were Probe-P sequence,TE= 144 or 35 ms,and both single voxel spectrum and chemical shift imging were included.The major parameters of DTI were diffusion directions =15,b value = 1000 s/mm^2. Frational anisotropic(FA) map and average ADC map were obtained to evaluate DTI result. Positive deletion ratio was observed and the imaging changes were compared between injured side and normal side.Results:All 21 patients had CT scan and Glasgow scale.A total of 19 patients had conventional MRI.DTI and MRS.Results of CT and conventional MRI showed no significant abnormality in lobe,and Glasgow scale showed mild type.MRS result showed significant decrease in N-acetyl aspartate(NAA) and NAA/creatine(Cr) in 13 cases(68.4%) (P【0.001),and increase in lactic acid(Lac) in 7 cases(36.8%).FA mapping of the frontal lobe displayed significant changes in 7 cases(36.8%),with 5 out of the 7 cases having increase in FA value.And there was no significant difference in average ADC.Conclusions:MRS and DTI might be more sensible than other methods,such as CT and conventional MRI in diagnosis of MTBI.The particular changes were reduced NAA and increased Lac for MRS.and increased FA values for DTI.
文摘A new proposal for spinal cord and brain treatment and protection due to injuries and diseases is made herein. It is composed of two 20G nylon catheters with 6 lateral holes arranged circumferentially within 3 cm from the tip and a closed end. One catheter is inserted into the epidural space and the other catheter is inserted into the spinal space in two different lumbar interspaces using an 18G Tuohy needle 90 mm. The epidural catheter is used for cooled saline injection and infusion. The spinal catheter is used for Intralipid spinal injections and CSF aspiration. The proposal is based on the current studies on spinal cord cooling and CSF aspiration as well as on the Intralipid resuscitation properties and lipid brain protection. A study is needed to evaluate the clinical value of this combined approach.
文摘Purpose: The aim of this study was to measure social participation in children with traumatic brain injuries (TBI) on their parental perceptions, retrospectively for the pre-injury period, at the beginning of rehabilitation and one year after return to school. Methods: This study was conducted among 17 children aged 5 to 17 years old with moderate or severe TBI and their parents. Social participation was assessed using the LIFE-H for Children (1.0). Results: A significant decrease (p ≤ 0.001) in the level of accomplishment of life habits was found for all categories between the measurements taken pre-injury and at the beginning of rehabilitation. Significant differences (p ≤ 0.002) related to the increase in the life habit accomplishment scores were also found between measurements taken at the beginning of rehabilitation and one year after return to school. Conclusion: TBI significantly affected the accomplishment of life habits of the participants compared to their pre-injury level. The assessment of social participation at various times provides a report on the client’s progress and allows clinicians to update his or her intervention plan, to plan follow-ups or to end the intervention. This knowledge must be considered by anyone involved in helping these children to achieve their greatest social participation.
文摘Introduction: Traumatic brain injury (TBI) in children is a common cause of emergency department admission to our institution. TBI constitutes a real public health problem in developed countries and marked increase in underdeveloped countries. The aim of this study was to evaluate the results of neurosurgical treatment of TBI in children at the neurosurgery department of Yopougon Teaching Hospital, while underlining the difficulties of the adequate management of this affection in Abidjan. Patients and Methods: It was a retrospective, descriptive monocentric study performed in the neurosurgery department, of Yopougon Teaching Hospital-Abidjan (Ivory Coast) from January 2000 to December 2017. We included all patients less than 16 years old admitted to the emergency department and all admitted in neurosurgery department for a TBI with a cerebral tomodensitometry and/or a magnetic resonance imaging having undergone a neurosurgical treatment. Results: During the study period 2825 cases of TBI in children aged less than 16 years old admitted to pediatric emergencies of our institution;among them 1020 (36%) presented clinical abnormalities and/or imaging. 292 (10.34%) children were hospitalized in neurosurgery department. 108 (36.9%) had surgical treatment. The mean age of patients was 7.8 ± 0.80 years with a male predominance (64%). Of the 108 children who had been operated on, 41 had acute extra-dural hematoma evacuation, 22 had a cranio-cerebral wound healing, 36 had a lift from a fracture depressing the skull and 9 had an acute subdural hematoma evacuation with a decompressive flap. The mean delay between diagnosis and surgical care was 104 ± 67.25 hours. The postoperative evolution at the last follow-up was favorable in 96 (88.8%) children with sequelae in 12 children (6 language disorders, 2 epileptic seizures and 4 motor deficits). The postoperative mortality rate was 11.2%. Conclusion: Ivory Coast Health System does not provide optimal care management of patients with TBI. There is an emerging imperative to develop an insurance system for the management of TBI.
文摘There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone(SVZ). However, a comprehensive understanding of SVZ cell responses to brain injuries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed flow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how flow cytometric analyses also have begun to reveal how specific cytokines, such as Leukemia inhibitory factor are coordinating SVZ responses to injury.
文摘To discuss the treatment of spine or spinal cord injuries combined with severe traumatic brain injuries and measures to decrease invalidity and mortality rate.Methods Forty-five cases with spine or spinal cord injuries combined with severe traumatic brain injuries were analyzed retrospectively.Results Among all the cases,26 were cured,14 were improved,5 died.Conclusion Early examination,early diagnosis and effective treatment are very improtant.Routine head CT plain scan and spine X-ray photographs are needed and 3 dimension CT check or MRI should also be taken if necessary.It has clinical significance to improve earlier period diagnosis rate and to decrease invalidity and mortality rate.5 refs,4 figs.
基金This study was supported by deputy of research,Kashan University of Medical Sciences(Grant no:99116).
文摘Purpose:Despite advances in modern medicine,traumatic brain injuries(TBIs)are still a major medical problem.Early diagnosis of TBI is crucial for clinical decision-making and prognosis.This study aims to compare the predictive value of Helsinki,Rotterdam,and Stockholm CT scores in predicting the 6-month outcomes in blunt TBI patients.Methods:This cohort study was conducted on blunt TBI patients of 15 years or older.All of them were admitted to the surgical emergency department of Shahid Beheshti Hospital in Kashan,Iran from 2020 to 2021 and had abnormal trauma-related findings on brain CT images.The patients’demographic data such as age,gender,history of comorbid conditions,mechanism of trauma,Glasgow coma scale,CT images,length of hospital stay,and surgical procedures were recorded.The Helsinki,Rotterdam,and Stockholm CT scores were simultaneously determined according to the existing guidelines.The included patients'6-month outcome was determined using the Glasgow outcome scale extended.M Data were analyzed by SPSS software version 16.0.Sensitivity,specificity,negative/positive predictive value and the area under the receiver operating characteristic curve were calculated for each test.The Kappa agreement coefficient and Kuder Richardson-20 were used to compare the scoring systems.Results:Altogether 171 TBI patients met the inclusion and exclusion criteria,with the mean age of(44.9±20.2)years.Most patients were male(80.7%),had traffic related injuries(83.1%)and mild TBIs(64.3%).Patients with lower Glasgow coma scale had higher Helsinki,Rotterdam,and Stockholm CT scores and lower Glasgow outcome scale extended scores.Among all the scoring systems,the Helsinki and Stockholm scores showed the highest agreement in predicting patients’outcomes(kappa=0.657,p<0.001).The Rotterdam scoring system had the highest sensitivity(90.1%)in predicting death of TBI patients,whereas the Helsinki scoring system had the highest sensitivity(89.8%)in predicting the 6-month outcome in TBI patients.Conclusion:The Rotterdam scoring system was superior in predicting death in TBI patients,whereas the Helsinki scoring system was more sensitive in predicting the 6-month outcome.
基金supported by the Natural Science Foundation of Beijing,No.L222126(to LD)。
文摘A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.
基金supported by the National Natural Science Foundation of China,Nos.81671671(to JL),61971451(to JL),U22A2034(to XK),62177047(to XK)the National Defense Science and Technology Collaborative Innovation Major Project of Central South University,No.2021gfcx05(to JL)+6 种基金Clinical Research Cen terfor Medical Imaging of Hunan Province,No.2020SK4001(to JL)Key Emergency Project of Pneumonia Epidemic of Novel Coronavirus Infection of Hu nan Province,No.2020SK3006(to JL)Innovative Special Construction Foundation of Hunan Province,No.2019SK2131(to JL)the Science and Technology lnnovation Program of Hunan Province,Nos.2021RC4016(to JL),2021SK53503(to ML)Scientific Research Program of Hunan Commission of Health,No.202209044797(to JL)Central South University Research Program of Advanced Interdisciplinary Studies,No.2023Q YJC020(to XK)the Natural Science Foundation of Hunan Province,No.2022JJ30814(to ML)。
文摘Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.
基金supported by the United States Department of Veterans Affairs Rehabilitation Research and Development Service (RR&D)[Merit Review Award numbers B3123-I/101 RX003123 and B3986-R/I01 RX003986-01A1]。
文摘Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.
文摘Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.
基金supported by Notional Institutes of Health Grant,No.1R01NS100710-01A1(to YX)。
文摘Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.
基金Division of Neurology,Cincinnati Children’s Hospital Medical Center(as a Medical Student Scholars Program award to ALM)。
文摘There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.
基金supported by the Sichuan Science and Technology Program,No.2023YFS0164 (to JC)。
文摘Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.
