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Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds
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作者 Xin-Rui Qi Ronald W.H.Verwer +4 位作者 Ai-Min Bao Rawien A.Balesar Sabina Luchetti Jiang-Ning Zhou Dick F.Swaab 《神经科学通报:英文版》 SCIE CAS CSCD 2019年第2期244-252,共9页
Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary... Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases.A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material. 展开更多
关键词 Alzheimer’s disease BRAIN bank Brain-derived neurotrophic factor Depression Electrical activity HUMAN BRAIN slice CULTURE Neuropsychiatric disorders ORGANOTYPIC CULTURE POSTMORTEM HUMAN BRAIN TISSUE Resected HUMAN BRAIN TISSUE
Brain Banking for Research into Neurodegenerative Disorders and Ageing
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作者 Claire E.Shepherd Holly Alvendia Glenda M.Halliday 《神经科学通报:英文版》 SCIE CAS CSCD 2019年第2期283-288,共6页
Advances in cellular and molecular biology underpin most current therapeutic advances in medicine.Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is beco... Advances in cellular and molecular biology underpin most current therapeutic advances in medicine.Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is becoming increasingly evident that greater access to human brain tissue is necessary to understand both the cellular biology of these diseases and their variation. Research in these areas is vital to the development of viable therapeutic options for these currently untreatable diseases. The development and coordination of human brain specimen collection through brain banks is evolving. This perspective article from the Sydney Brain Bank reviews data concerning the best ways to collect and store material for different research purposes. 展开更多
关键词 BRAIN BANKING BRAIN DONATION NEURODEGENERATIVE DISEASES Human BRAIN TISSUE processing
脑科学研究——生命科学最大的挑战 预览
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作者 孙涛 李信晓 《宁夏医科大学学报》 2019年第1期1-6,共6页
随着社会、经济的发展及人们认知的提高,脑科学研究已成为全世界科学研究的热点之一。新兴技术的出现极大促进了脑科学研究,为揭示大脑功能、运作机制和治疗脑疾病方面起到了重要作用。通过脑科学的基础研究、临床研究和基于脑研究大数... 随着社会、经济的发展及人们认知的提高,脑科学研究已成为全世界科学研究的热点之一。新兴技术的出现极大促进了脑科学研究,为揭示大脑功能、运作机制和治疗脑疾病方面起到了重要作用。通过脑科学的基础研究、临床研究和基于脑研究大数据信息的挖掘,为类脑研究项目的开展奠定了基础。同时,脑的发育与衰老、学习与记忆、认知与情绪、意识与精神及各脑区的结构功能研究成为人类不断认识世界、认识自我、超越自我的最终挑战。脑科学研究被称为生命科学最后的疆域,是现代认知科学乃至整个生命科学面临的最大挑战,因此,脑科学研究对提高人们的健康水平、生活质量和创新能力具有重要的现实意义。 展开更多
关键词 大脑 人类脑计划 脑区 人工智能
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Acute drivers of neuroinflammation in traumatic brain injury 预览
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作者 Kathryn L.Wofford David J.Loane D.Kacy Cullen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第9期1481-1489,共9页
Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology.Immune cells respond to acute signals from damaged cells,initiate neuroinflammation,and drive the patho... Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology.Immune cells respond to acute signals from damaged cells,initiate neuroinflammation,and drive the pathological consequences over time.Importantly,the mechanism(s)of injury,the location of the immune cells within the brain,and the animal species all contribute to immune cell behavior following traumatic brain injury.Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration.Within this paper,we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury. 展开更多
关键词 traumatic BRAIN INJURY inflammation NEUROINFLAMMATION MICROGLIA macrophage ACUTE diffuse BRAIN INJURY cytokines ADENOSINE 5′-triphosphoate glutamate calcium
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Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain 预览
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作者 Xiao-He Gu Heng Li +4 位作者 Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期270-276,共7页
Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neu... Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016. 展开更多
关键词 Δ78 locus BRAIN region dopaminergic neurons glial cell line-derived NEUROTROPHIC factor mouse BRAIN precursor protein α-pro-GDNF β-pro-GDNF sorting protein-related receptor with A-TYPE REPEATS splice variants
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Vascular endothelial growth factor A promotes platelet adhesion to collagen Ⅳ and causes early brain injury after subarachnoid hemorrhage 预览
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作者 Zun-Wei Liu Jun-Jie Zhao +1 位作者 Hong-Gang Pang Jin-Ning Song 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1726-1733,共8页
The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to p... The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015. 展开更多
关键词 nerve REGENERATION VASCULAR ENDOTHELIAL GROWTH FACTOR A VASCULAR ENDOTHELIAL GROWTH FACTOR receptor 2 subarachnoid hemorrhage brain injuries platelet adhesion COLLAGEN blood-brain barrier neural REGENERATION
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Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury 预览
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作者 Feng Yan Ming Li +7 位作者 Hong-Qi Zhang Gui-Lin Li Yang Hua Ying Shen Xun-Ming Ji Chuan-Jie Wu Hong An Ming Ren 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1780-1786,共7页
Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury.Porous collagen-chitosan scaffolds were pr... Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury.Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering.The scaffolds were impregnated with rat bone marrow mesenchymal stem cells.A traumatic brain injury rat model was established using the 300 g weight free fall impact method.Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain.Modified neurological severity scores were used to assess the recovery of neurological function.The Morris water maze was employed to determine spatial learning and memory abilities.Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue.Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine(BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein.Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores,shortened the average latency of the Morris water maze,increased the number of platform crossings,diminished the degeneration of damaged brain tissue,and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas.At 14 days after transplantation,increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area.The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone.To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds,immunosuppressive cyclosporine was intravenously inject 展开更多
关键词 nerve REGENERATION STEM CELLS COLLAGEN chitosan scaffolds traumatic BRAIN injury bone MARROW mesenchymal STEM CELLS BRAIN tissue engineering neural REGENERATION
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Differences in pathological changes between two rat models of severe traumatic brain injury 预览
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作者 Yi-Ming Song Yu Qian +6 位作者 Wan-Qiang Su Xuan-Hui Liu Jin-Hao Huang Zhi-Tao Gong Hong-Liang Luo Chuang Gao Rong-Cai Jiang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第10期1796-1804,共9页
The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model u... The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relat 展开更多
关键词 nerve REGENERATION severe traumatic brain INJURY animal model comparison free weight drop controlled cortical impact NEUROLOGICAL impairment NEUROINFLAMMATION blood-brain barrier damage neuronal apoptosis diffuse AXONAL INJURY BRAINSTEM INJURY neural REGENERATION
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Traumatic axonal injury of the cingulum in patients with mild traumatic brain injury:a diffusion tensor tractography study 预览
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作者 Sung Ho Jang Seong Ho Kim Han Do Lee 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第9期1556-1561,共6页
The cingulum,connecting the orbitofrontal cortex to the medial temporal lobe,involves in diverse cognition functions including attention,memory,and motivation.To investigate the relationship between the cingulum injur... The cingulum,connecting the orbitofrontal cortex to the medial temporal lobe,involves in diverse cognition functions including attention,memory,and motivation.To investigate the relationship between the cingulum injury and cognitive impairment in patients with chronic mild traumatic brain injury,we evaluated the integrity between the anterior cingulum and the basal forebrain using diffusion tensor tractography in 73 patients with chronic mild traumatic brain injury(39 males,34 females,age 43.29±11.42 years)and 40 healthy controls(22 males,18 females,age 40.11±16.81 years).The patients were divided into three subgroups based on the integrity between the anterior cingulum and the basal forebrain on diffusion tensor tractography:subgroup A(n=19 patients)– both sides of the anterior cingulum were intact;subgroup B(n=36 patients)– either side of the anterior cingulum was intact;and subgroup C(18 patients)– both sides of the anterior cingulum were discontinued.There were significant differences in total Memory Assessment Scale score between subgroups A and B and between subgroups A and C.There were no significant differences in diffusion tensor tractography parameters(fractional anisotropy,apparent diffusion coefficient,and fiber volume)between patients and controls.These findings suggest that the integrity between the anterior cingulum and the basal forebrain,but not diffusion tensor tractography parameter,can be used to predict the cognitive function of patients with chronic mild traumatic brain injury.This study was approved by Yeungnam University Hospital Institutional Review Board(approval No.YUMC-2014-01-425-010)on August 16,2017. 展开更多
关键词 mild traumatic BRAIN injury BRAIN trauma DIFFUSION TENSOR TRACTOGRAPHY DIFFUSION TENSOR imaging cognitive impairment CINGULUM memory Glasgow COMA Scale neural regeneration
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Whole-brain radiation therapy alone vs.combined therapy with stereotactic radiosurgery for the treatment of limited brain metastases:A systematic review 预览
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作者 Chao Wan Biao Chen +1 位作者 Yuanshi Liu Ximing Xu 《肿瘤学与转化医学:英文版》 2019年第3期114-118,共5页
Objective The aim of the study was to compare the efficacy and safety of whole brain radiotherapy(WBRT) used alone and combined with stereotactic radiosurgery(SRS) in the treatment of limited(1–4)brain metastases. Me... Objective The aim of the study was to compare the efficacy and safety of whole brain radiotherapy(WBRT) used alone and combined with stereotactic radiosurgery(SRS) in the treatment of limited(1–4)brain metastases. Methods We searched for randomized controlled and matched-pair analysis trials comparing WBRT plus SRS versus WBRT alone for brain metastases. The primary outcomes were the overall survival(OS), intracranial control(IC), and localcontrol(LC). The secondary outcome was radiation toxicity. The log hazard ratios(lnHRs) and their variances were extracted from published Kaplan-Meier curves and pooled using the generic inverse variance method in the RevMan 5.3 software. The non-pooled outcome measures were evaluated using descriptive analysis. Results Three randomized controlled trials and two matched-pair analysis studies were included. There was no difference in the OS for limited brain metastases between the two groups [lnHR 0.91(95% CI 0.76–1.09, P = 0.32) vs. 0.72(95% CI 0.44–1.19, P = 0.20)]. The LC and IC were significantly higher in the combined treatment group [lnHR 0.69(95% CI 0.55–0.86, P = 0.001) vs. 0.41(95% CI 0.29–0.58, P < 0.0001)]. For patients with a single lesion, one trial showed a higher survival in the combined treatment group(median OS: 6.5 months vs. 4.9 months, P = 0.04). The combined treatment was not associated with significantly higher incidence of radiation toxicity. Conclusion Combined treatment with WBRT plus SRS should be recommended for patients with limited brain metastases based on the better LC and IC without increased toxicity. It should also be considered a routine treatment option for patients with solitary brain metastases based on the prolonged OS. 展开更多
关键词 LIMITED BRAIN METASTASES STEREOTACTIC radiosurgery(SRS) whole BRAIN radiotherapy(WBRT) systematic review
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紫草素对缺血性脑损伤大鼠脑组织保护作用的研究 预览
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作者 朱丹 汪立刚 徐蕾 《解放军医药杂志》 CAS 2019年第7期1-4,共4页
目的 探讨紫草素对缺血性脑损伤大鼠脑组织的保护作用及其机制。方法 选取48只大鼠,随机分为假手术组、模型组和紫草素治疗组,每组16只。制备缺血性脑损伤大鼠模型,观察3组大鼠日常行为,并对大鼠脑组织进行病理学观察,用酶联免疫吸附试... 目的 探讨紫草素对缺血性脑损伤大鼠脑组织的保护作用及其机制。方法 选取48只大鼠,随机分为假手术组、模型组和紫草素治疗组,每组16只。制备缺血性脑损伤大鼠模型,观察3组大鼠日常行为,并对大鼠脑组织进行病理学观察,用酶联免疫吸附试验测定3组脑组织中白介素-6(IL-6)和IL-8含量,蛋白免疫印迹法检测3组脑核因子-κB(NF-κB)蛋白表达水平。结果 模型组动物活动减少,部分动物出现躁动。假手术组大鼠皮层及海马区锥体神经元层次分明;模型组皮层及海马区神经细胞层次紊乱,密度降低;紫草素治疗组可以改善缺血性脑损伤大鼠脑组织神经元的异常形态变化。假手术组神经元形态基本正常;模型组神经元细胞胞质内空泡形成,细胞核内染色质边集;紫草素治疗组神经元细胞状态有所好转,细胞变性程度较模型组缓解。紫草素治疗组IL-6和IL-8表达量及NF-κB蛋白表达水平均低于模型组(P<0.01)。结论 紫草素对缺血性脑损伤大鼠有一定改善作用。 展开更多
关键词 缺氧缺血 脑损伤 紫草素 核因子-ΚB 大鼠 Sprague-Dawley
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Extract of Yokukansan improves anxiety-like behavior and increases serum brain-derived neurotrophic factor in rats with cerebral ischemia combined with amyloid-β42 peptide
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作者 Ai Nogami-Hara Kaori Kubota +8 位作者 Kotaro Takasaki Takuya Watanabe Nobuaki Egahira Hikari Iba Risako Fujikawa Shutaro Katsurabayashi Funda Bolukbasi Hatip Izzettin Hatip-Al-Khatib Katsunori Iwasaki 《中医杂志:英文版》 SCIE CAS CSCD 2019年第1期50-58,共9页
OBJECTIVE: To examine the effects of Yokukansan(YKS) extract on two endogenous modulators of anxiety, brain-derived neurotrophic factor(BDNF)and serotonin (5-HT)2A receptors pharmacologically, in the ischemic rat mode... OBJECTIVE: To examine the effects of Yokukansan(YKS) extract on two endogenous modulators of anxiety, brain-derived neurotrophic factor(BDNF)and serotonin (5-HT)2A receptors pharmacologically, in the ischemic rat model of dementia.METHODS: The cerebral ischemia(CI) was induced by bilateral occlusion of the vertebral and common carotid arteries(4-vessel occlusion ischemia). The CI was combined with the amyloid-β42 peptide(A42) injected intracerebroventricularly, and referreβdto as CI+Aβ. Anxiety-like behaviors were assessed by elevated plus maze(enclosed arm), light/dark transition test(dark chamber), and open-field test.Wet-dog shakes were induced by the 5-HT2A receptor agonist 2, 5-dimethoxy-4-iodoamphetamine(DOI). The concentration of BDNF in serum was determined by enzyme-linked immuno sorbent assay.RESULTS: CI + Aβ increased anxiety, as demonstrated by the increase of time spent in the enclosed arms and dark chambers, and locomotion in the outer zone of the open field(thigmotaxis). CI + Adecreased the serum concentration of BDNF. YKS reβ-duced the anxiety-like behaviors, suppressed the DOI-induced wet-dog shakes and increased serum BDNF concentrations.CONCLUSION: Our findings suggest that YKS extract improves CI + Aβ-induced anxiety by antagonizing 5-HT2A receptors and increasing BDNF. 展开更多
关键词 Brain ischemia AMYLOID beta-peptides Anxiety BRAIN-DERIVED NEUROTROPHIC factor Receptor SEROTONIN 5-HT2A Yokukansan
Microglial cathepsin B as a key driver of inflammatory brain diseases and brain aging 预览
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作者 Hiroshi Nakanishi 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期25-29,共5页
Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke an... Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging. 展开更多
关键词 brain aging CASPASE-1 cathepsin B inflammatory brain diseases INTERLEUKIN-1Β MICROGLIA mitochondrial transcription factor A NEUROINFLAMMATION nuclear factor-κB oxidative stress
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MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis 预览
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作者 Nan-Xing Yi Long-Yun Zhou +8 位作者 Xiao-Yun Wang Yong-Jia Song Hai-Hui Han Tian-Song Zhang Yong-Jun Wang Qi Shi Hao Xu Qian-Qian Liang Ting Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期1919-1931,共13页
OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injur... OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces b 展开更多
关键词 nerve REGENERATION acute BRAIN injury NEUROLOGICAL function spatial cognition water MAZE test LESION volume BRAIN edema rat systematic review META-ANALYSIS neural REGENERATION
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Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
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作者 Caifang Gao Jianming Liang +6 位作者 Ying Zhu Chengli Ling Zhekang Cheng Ruixiang Li Jing Qin Weigen Lu Jianxin Wang 《药学学报:英文版》 CSCD 2019年第4期843-857,共15页
Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many... Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers.Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs.The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy. 展开更多
关键词 GLIOMA CASEIN MENTHOL NANOPARTICLES BRAIN targeting Blood–brain barrier 10-HYDROXYCAMPTOTHECIN
Decreased numbers of circulating endothelial progenitor cells are associated with hyperglycemia in patients with traumatic brain injury 预览
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作者 Hui-Jie Wei Li Liu +7 位作者 Fang-Lian Chen Dong Wang Liang Wang Zeng-Guang Wang Rong-Cai Jiang Jing-Fei Dong Jie-Li Chen Jian-Ning Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期984-990,共7页
Hyperglycemia reduces the number of circulating endothelial progenitor cells,accelerates their senescence and impairs their function.However,the relationship between blood glucose levels and endothelial progenitor cel... Hyperglycemia reduces the number of circulating endothelial progenitor cells,accelerates their senescence and impairs their function.However,the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear.In this study,101 traumatic brain injury patients admitted to the Department of Neurosurgery,Tianjin Medical University General Hospital or the Department of Neurosurgery,Tianjin Huanhu Hospital,China,were enrolled from April 2005 to March 2007.The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1,4,7,14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis,respectively.The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined.Compared with controls,the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury,and then increased at 4 days after injury,and reached a peak at 7 days after injury.Compared with controls,blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable.At 1,4,and 7 days after injury,the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r=?0.147,P<0.05).Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells.This study was approved by the Ethical Committee of Tianjin Medical University General Hospital,China(approval No.200501)in January 2015. 展开更多
关键词 nerve REGENERATION endothelial progenitor cells VASCULAR repair VASCULAR remodeling angiogenesis NEOVASCULARIZATION blood glucose HYPERGLYCEMIA traumatic BRAIN injury MOBILIZATION suppression senescence alternative therapy BRAIN damage neural REGENERATION
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Brain activation induced by different strengths of hand grasp:a functional magnetic resonance imaging study 预览
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作者 Hyeok Gyu Kwon Ju Sang Kim Mi Young Lee 《中国神经再生研究:英文版》 CSCD 2020年第5期875-879,共5页
Mirror neuron system can be activated by observation and execution of an action.It has an important function of action understanding.We investigated brain activations in humans by observing the strength of a hand gras... Mirror neuron system can be activated by observation and execution of an action.It has an important function of action understanding.We investigated brain activations in humans by observing the strength of a hand grasp using functional magnetic resonance imaging.Twenty right-handed healthy individuals,consisting of 10 males and 10 females,aged 22.40 ± 2.04 years,were recruited into this study from September to November 2017 via posters.Light hand grasp task video showed a hand lightly grasping and releasing a ball repeatedly.Powerful hand grasp task video showed a hand tightly grasping and releasing a ball repeatedly.Functional magnetic resonance imaging block design paradigm comprised five stimulation blocks alternating with five baseline blocks.Stimulation blocks were presented with two stimulus tasks,consisting of a light grasp and a powerful grasp.Region of interest was defined around the inferior parietal lobule,inferior frontal gyrus,and superior temporal sulcus which have been called mirror neuron system.The inferior parietal lobule,fusiform,postcentral,occipital,temporal,and frontal gyri were activated during light and powerful grasp tasks.The BOLD signal response of a powerful grasp was stronger than that of a light grasp.These results suggest that brain activation of the inferior parietal lobule,which is the core brain region of the mirror neuron system,was stronger in the powerful grasp task than in the light grasp task.We believe that our results might be helpful for instructing rehabilitation of brain injury.This study was approved by the Institutional Review Board of Daegu Oriental Hospital of Daegu Haany University on September 8,2017 (approval No.DHUMC-D-17020-PRO-01). 展开更多
关键词 BRAIN activation fMRI human BRAIN INFERIOR PARIETAL lobule light GRASP mirror NEURON system POWERFUL GRASP
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微小RNA在新生儿缺血缺氧性脑病中的表达 预览
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作者 王丽敏 顾珺 沈朝斌 《中华妇幼临床医学杂志(电子版)》 CAS 2019年第5期497-503,共7页
微小RNA(miRNA)是一类高度保守的内源性小分子RNA。miRNA主要通过选择性结合mRNA调控基因表达。目前研究结果表明,中枢神经系统存在大量miRNA,并参与神经细胞的正常生长、发育,以及组织损伤修复、肿瘤发生、神经退行性变等多种病理、生... 微小RNA(miRNA)是一类高度保守的内源性小分子RNA。miRNA主要通过选择性结合mRNA调控基因表达。目前研究结果表明,中枢神经系统存在大量miRNA,并参与神经细胞的正常生长、发育,以及组织损伤修复、肿瘤发生、神经退行性变等多种病理、生理过程。笔者拟就新生儿缺血缺氧性脑病(HIE)miRNA谱系的最新研究进展进行阐述,探讨其miRNA特异性表达,对新生儿HIE诊断和预后判断的意义,旨在为该病的相关诊治研究提供参考。 展开更多
关键词 微RNAS 核糖核酸酶类 缺氧缺血 脑损伤 分子靶向治疗 微小RNA拟似物 婴儿 新生
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Resting-state network complexity and magnitude changes in neonates with severe hypoxic ischemic encephalopathy 预览
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作者 Hong-Xin Li Min Yu +4 位作者 Ai-Bin Zheng Qin-Fen Zhang Guo-Wei Hua Wen-Juan Tu Li-Chi Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第4期642-648,共7页
Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy.However,the specific brain networks implicated in neonatal cases remain... Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy.However,the specific brain networks implicated in neonatal cases remain poorly understood.In this study,we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children’s Hospital,China.Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups.However,compared with the mild hypoxic ischemic encephalopathy group,the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient.The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group.Moreover,nodal efficiency was reduced in the left rolandic operculum,left supramarginal gyrus,bilateral superior temporal gyrus,and right middle temporal gyrus.These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy,and may be associated with impaired language,motion,and cognition.These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy,enabling early interventions targeting brain function.This study was approved by the Regional Ethics Review Boards of the Changzhou Children’s Hospital(approval No.2013-001)on January 31,2013.Informed consent was obtained from the family members of the children.The trial was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR1800016409)and the protocol version is 1.0. 展开更多
关键词 nerve REGENERATION NEONATES hypoxic ischemic encephalopathy RESTING-STATE FUNCTIONAL magnetic resonance imaging BRAIN networks SMALL-WORLD organization BRAIN FUNCTIONAL connectivity local efficiency clustering coefficient neural REGENERATION
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新生未成熟大鼠缺氧缺血性脑损伤时微小RNA-200b对缺氧诱导因子1α的调控作用 被引量:1
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作者 高笑妮 杨丽君 +1 位作者 张囡 崔红 《中华新生儿科杂志(中英文)》 CAS 2019年第1期58-62,共5页
目的 探讨新生未成熟大鼠缺氧缺血性脑损伤(hypoxic ischemic brain damage,HIBD)时微小RNA 200b(micro RNA-200b,miR-200b)对缺氧诱导因子1α(hypoxia-inducible factors-1α,HIF-1α)的调控作用,为早产儿HIBD的治疗提供思路。 方法 选... 目的 探讨新生未成熟大鼠缺氧缺血性脑损伤(hypoxic ischemic brain damage,HIBD)时微小RNA 200b(micro RNA-200b,miR-200b)对缺氧诱导因子1α(hypoxia-inducible factors-1α,HIF-1α)的调控作用,为早产儿HIBD的治疗提供思路。 方法 选取3日龄新生Sprague-Dawley(SD)大鼠240只,随机分为单纯缺氧缺血组(HI组)、造模后双侧侧脑室注射miR-200b激动剂组、注射miR-200b拮抗剂组、注射miR-200b激动剂阴性对照剂组、注射miR-200b拮抗剂阴性对照剂组和正常对照组,每组40只。除正常对照组不予特殊处理外,其他各组均建立未成熟新生大鼠HIBD模型。应用实时定量聚合酶链反应检测各组大鼠侧脑室注射后12 h、1 d、3 d和7 d脑组织中HIF-1α的相对表达量,比较HIF-1α表达的变化。 结果 (1)与正常对照组比较,单纯HI组侧脑室注射生理盐水后12 h HIF-1α表达量开始升高,1 d达高峰,差异有统计学意义(P<0.05),随后逐渐下降,7 d与正常对照组接近,差异无统计学意义(P>0.05)。(2)单纯HI组与HI miR-200b激动剂阴性对照组及HI miR-200b拮抗剂阴性对照组HIF-1α表达量比较,差异无统计学意义(P>0.05),miR-200b纳米载体对HIF-1α表达无明显影响。(3)HI miR-200b拮抗剂组HIF-1α持续处于高表达状态,12 h明显高于单纯HI组,差异有统计学意义(P<0.05);注射后1、3、7 d HI miR-200b拮抗剂组与单纯HI组比较,差异无统计学意义(P>0.05)。HI miR-200b激动剂组HIF-1α表达持续低于单纯HI组,1 d时差异有统计学意义(P<0.05)。 结论 miR-200b过度表达抑制了HIF-1α表达,miR-200b低表达可上调HIF-1α表达水平,但作用时间有限。因此miR-200b有可能通过调控HIF-1α的表达参与新生大鼠HIBD后减轻脑损伤的调节。 展开更多
关键词 缺氧缺血 脑损伤 微小RNA-200b 缺氧诱导因子1 Α亚基 大鼠
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