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Gut microbial regulation of innate and adaptive immunity after traumatic brain injury 被引量:4
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作者 Marta Celorrio Kirill Shumilov Stuart H.Friess 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期272-276,共5页
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
关键词 gut microbiome gut microbiota gut-brain axis macrophage MICROGLIA MONOCYTE NEUROINFLAMMATION short-chain fatty acids T cell traumatic brain injury
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Advantages of nanocarriers for basic research in the field of traumatic brain injury 被引量:2
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作者 Xingshuang Song Yizhi Zhang +1 位作者 Ziyan Tang Lina Du 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期237-245,共9页
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
关键词 blood-brain barriers brain targeting central nervous system extracellular vesicles inflammatory factor microglial cell NANOCARRIERS nanoparticles neural restoration traumatic brain injury
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Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration 被引量:2
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作者 Shihong Zhu Xiaoyin Liu +7 位作者 Xiyue Lu Qiang Liao Huiyang Luo Yuan Tian Xu Cheng Yaxin Jiang Guangdi Liu Jing Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第10期2157-2174,共18页
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
关键词 bioactive materials BIOMATERIALS EXOSOMES neural regeneration scaffolds stem cells tissue engineering traumatic brain injury
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P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis 被引量:2
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作者 Zhiqing Yang Zhenchao Wang +4 位作者 Xiaoqi Deng Lingxin Zhu Zhaomeng Song Changyu Cao Xinran Li 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1078-1083,共6页
Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea... Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis. 展开更多
关键词 APOPTOSIS AUTOPHAGY CORTEX HIPPOCAMPUS motor function P7C3-A20 traumatic brain injury
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Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration 被引量:2
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作者 Ye Xiong Asim Mahmood Michael Chopp 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期49-54,共6页
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
关键词 biomarkers extracellular vesicles functional outcome mesenchymal stem/stromal cells NEUROINFLAMMATION NEUROPLASTICITY NEUROPROTECTION traumatic brain injury
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Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis 被引量:2
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作者 Mingxiang Ding Lei Jin +4 位作者 Boyang Wei Wenping Cheng Wenchao Liu Xifeng Li Chuanzhi Duan 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1064-1071,共8页
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have... Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis. 展开更多
关键词 ASTROCYTE early brain injury INFLAMMASOME NLRC4 PYROPTOSIS subarachnoid hemorrhage tumor necrosis factor-stimulated gene-6(TSG-6)
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Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury 被引量:1
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作者 Nikita Ollen-Bittle Austyn D.Roseborough +2 位作者 Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第10期2119-2131,共13页
Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial ac... Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury. 展开更多
关键词 axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation NEUROINFLAMMATION traumatic brain injury
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Application of artificial hibernation technology in acute brain injury 被引量:1
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作者 Xiaoni Wang Shulian Chen +5 位作者 Xiaoyu Wang Zhen Song Ziqi Wang Xiaofei Niu Xiaochu Chen Xuyi Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期1940-1946,共7页
Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment ... Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application. 展开更多
关键词 cute brain injury artificial hibernation HYPOTHERMIA low metabolism mild hypothermia
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Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury 被引量:1
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作者 Dan Yang Bin-Bin Nie +6 位作者 Jin-Gang He Zong-Qiang Lv Feng-Feng Mo Si-Yi Ouyang Jie Wang Ju-Xiang Chen Tao Tao 《Zoological Research》 SCIE CSCD 2024年第3期648-662,共15页
Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact... Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment. 展开更多
关键词 Post-traumatic headache(PTH) Mild traumatic brain injury(mTBI) Metabolic kinetics FMRI CEREBELLUM
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The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury 被引量:2
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作者 Yijing Zhao Tong Li +6 位作者 Zige Jiang Chengcheng Gai Shuwen Yu Danqing Xin Tingting Li Dexiang Liu Zhen Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1084-1091,共8页
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r... We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury. 展开更多
关键词 chemokine(C-X-C motif)ligand 11 cystathionineβsynthase H2S hypoxic ischemic brain injury inflammation L-CYSTEINE lipopolysaccharide microglia miR-9-5p neuroprotection
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Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury 被引量:1
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作者 Jingzhou Liu Xin Xin +8 位作者 Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第3期629-635,共7页
Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogr... Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury. 展开更多
关键词 AAV9P1 ASTROCYTES astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury
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Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice 被引量:1
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作者 Weilin Tan Jun Ma +9 位作者 Jiayuanyuan Fu Biying Wu Ziyu Zhu Xuekang Huang Mengran Du Chenrui Wu Ehab Balawi Qiang Zhou Jie Zhang Zhengbu Liao 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期171-179,共9页
Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate trau... Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway. 展开更多
关键词 axon guidance bioinformatics analysis competing endogenous RNA ERYTHROPOIETIN Gene Ontology Kyoto Encyclopedia of Genes and Genomes non-coding RNA RNA sequencing transcriptomics traumatic brain injury
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Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review
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作者 Avery L.Miller Nathan K.Evanson J.Michael Taylor 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1686-1695,共10页
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
关键词 acetylcholinesterase inhibitor ADULT COGNITION DONEPEZIL PEDIATRICS traumatic brain injury
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Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury
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作者 Qian Zhang Yao Jing +10 位作者 Qiuyuan Gong Lin Cai Ren Wang Dianxu Yang Liping Wang Meijie Qu Hao Chen Yaohui Tang Hengli Tian Jun Ding Zhiming Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1092-1097,共6页
Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavio... Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways. 展开更多
关键词 ANGIOGENESIS controlled cortical impact endorepellin neurological function traumatic brain injury
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Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis
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作者 Sihong Huang Jungong Han +4 位作者 Hairong Zheng Mengjun Li Chuxin Huang Xiaoyan Kui Jun Liu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第7期1553-1558,共6页
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
关键词 cognitive function CROSS-SECTION FOLLOW-UP functional connectivity graph theory longitudinal study mild traumatic brain injury prediction small-worldness structural connectivity subnetworks whole brain network
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Neurotrophins and neural stem cells in posttraumatic brain injury repair
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作者 Wenwen Guo Ke Liu +6 位作者 Yinghua Wang Xu Ge Yifan Ma Jing Qin Caiqin Zhang Ya Zhao Changhong Shi 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第1期12-23,共12页
Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and test... Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and tested to mitigate neurological decline,a definitive cure for these conditions remains elusive.Studies have revealed that vari-ous neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation,apoptosis,blood-brain barrier permeability,neurite regeneration,and memory function.These factors are instrumental in alleviating neu-roinflammation and promoting neuroregeneration.In addition,neural stem cells(NSC)contribute to nerve repair through inherent neuroprotective and immunomodulatory properties,the release of neurotrophins,the activation of endogenous NSCs,and in-tercellular signaling.Notably,innovative research proposals are emerging to combine BDNF and NSCs,enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI.In this review,we summarize the mechanism of neurotrophins in promoting neurogen-esis and restoring neural function after TBI,comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI,and investigate their interaction with NSCs.This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI,thereby promoting the progress of TBI therapeutics. 展开更多
关键词 mutual effect neural stem cells neurological function NEUROTROPHINS traumatic brain injury
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Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases
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作者 PING YANG YUANXIANG LAN +2 位作者 ZHONG ZENG YAN WANG HECHUN XIA 《BIOCELL》 SCIE 2024年第1期149-162,共14页
Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-t... Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of action.Material&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in vitro.Our primary objective is to provide evidence supporting the clinical application of PDMSCs.Results:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after CCI.PDMSCs,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal vein.This intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted rats.In the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional media.Notably,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and TIMP-2.Conclusion:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI. 展开更多
关键词 Traumatic brain injury Mesenchymal stem cells Oxidative stress Matrix metalloproteinases
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Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models
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作者 Sanika M.Joshi Theresa Currier Thomas Nafisa M.Jadavji 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1728-1733,共6页
Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemi... Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals. 展开更多
关键词 folic acid NICOTINAMIDE one-carbon metabolism RIBOFLAVIN traumatic brain injury vitamin B12 vitamin B2 vitamin B3
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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis
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作者 Jing Wang Bing Zhang +9 位作者 Lanfang Li Xiaomei Tang Jinyu Zeng Yige Song Chao Xu Kai Zhao Guoqiang Liu Youming Lu Xinyan Li Kai Shu 《Neural Regeneration Research》 SCIE CAS 2025年第3期821-835,共15页
Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ... Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction. 展开更多
关键词 complement C1 dendrite dentate gyrus hippocampus neural stem cell NEUROGENESIS NEUROINFLAMMATION neurological function neuron traumatic brain injury
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Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats
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作者 Shigeharu Tsuda Mustafa Golam +3 位作者 Jiamei Hou Kevin K.W.Wang Floyd J.Thompson Prodip Bose 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第7期1548-1552,共5页
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
关键词 balance blood flow cardiovascular system central nervous system EPINEPHRINE ischemic damage lumbar spinal cord muscle tone repeated blast SPASTICITY traumatic brain injury
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