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Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage 预览
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作者 Hideki Kanamaru Hidenori Suzuki 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第7期1138-1143,共6页
Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial ... Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage. 展开更多
关键词 blood-brain barrier early brain injury ENDOTHELIAL cell SUBARACHNOID HEMORRHAGE TIGHT junction inflammation matricellular protein TOLL-LIKE receptor 4 TLR4
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星蒌承气汤对脑出血大鼠炎性反应与血脑屏障通透性的影响 预览
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作者 周喜燕 李彬 牛昱光 《中医临床研究》 2019年第14期6-9,共4页
目的:探讨星蒌承气汤对脑出血大鼠血清肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)、白介素-1β(Interleukin-1β,IL-1β)水平、血脑屏障通透性的影响。方法:72只SPF级SD雄性大鼠随机分为假手术组、病证结合组、治疗组,每组各24... 目的:探讨星蒌承气汤对脑出血大鼠血清肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)、白介素-1β(Interleukin-1β,IL-1β)水平、血脑屏障通透性的影响。方法:72只SPF级SD雄性大鼠随机分为假手术组、病证结合组、治疗组,每组各24只。采用自体粪便灌胃法及胶原酶立体定位注射法复制痰热腑实证脑出血大鼠模型。治疗组星蒌承气汤灌胃;病证结合组、假手术组灌服等量生理盐水。评估各组大鼠不同时间点神经功能缺损评分;检测血清IL-1β、TNF-α水平;测量血肿周围脑组织伊文思蓝(Evens Blue,EB)含量。结果:星蒌承气汤可明显减轻痰热腑实证脑出血大鼠的神经功能缺损体征,同时明显降低大鼠血清TNF-α、IL-1β水平、血肿周围脑组织EB含量,且治疗组优于病证结合组(P<0.05)。结论:星蒌承气汤治疗后随着痰热腑实证脑出血大鼠神经功能缺损症状的减轻,大鼠的血清TNF-α、IL-1β水平较前降低,血肿周围脑组织EB含量明显降低,从而起到保护血脑屏障、减轻脑水肿,保护脑细胞的作用。 展开更多
关键词 星蒌承气汤 脑出血 炎性因子 血脑屏障 脑组织含水量
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Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro 预览
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作者 Chang-Xiang Li Xue-Qian Wang +3 位作者 Fa-Feng Cheng Xin Yan Juan Luo Qing-Guo Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期1941-1949,共9页
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin an... Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression o 展开更多
关键词 hyodeoxycholic acid oxygen glucose deprivation and REOXYGENATION blood-brain barrier permeability anti-oxidative anti-inflammatory ANTI-APOPTOTIC BRAIN-DERIVED NEUROTROPHIC FACTOR glial cell line-derived NEUROTROPHIC FACTOR ischemic stroke in vitro NEUROVASCULAR unit
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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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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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Lessons from glaucoma:rethinking the fluid-brain barriers in common neurodegenerative disorders 预览
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作者 Francisco Javier Carreras 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期962-966,共5页
Glaucoma has been recently characterized as a member of the group of anoikis-related diseases.Anoikis,a form of apoptosis,can be triggered by the unfastening of adherent junctions present in astrocytes.In those areas ... Glaucoma has been recently characterized as a member of the group of anoikis-related diseases.Anoikis,a form of apoptosis,can be triggered by the unfastening of adherent junctions present in astrocytes.In those areas of the central nervous system in which the soma of the neurons or their axons and dendrites are metabolically dependent on the activity of astrocytes,a derangement of the lactate shuttle caused by a separation between the plasma membranes of neurons and astrocytes would result in metabolic impairment of the neurons themselves.In glaucoma,the triggering event has been attributed to the posterior deviation of aqueous humor towards the astrocyte-rich prelaminar tissue of the optic nerve head.The mean calcium content in the aqueous is able to interfere with calcium-dependent adherent junctions and induce anoikis of the astrocytes.As the cerebrospinal fluid has a similar base calcium concentration,a shunt of cerebrospinal fluid through the cerebral parenchyma would be able to interfere in the astrocytic architecture with dire consequences to the metabolically dependent neurons.Here the similitude between glaucoma,amyotrophic lateral sclerosis and Alzheimer’s disease are discussed and the concept of the break in the fluid-brain barrier,as an event separated from the blood-brain barrier,is stressed. 展开更多
关键词 fluid-brain barriers blood-brain barrier CEREBROSPINAL FLUID aqueous humor calcium ion GLAUCOMA amyotrophic lateral SCLEROSIS Alzheimer’s disease
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血脑屏障通透性定量评估及其在急性缺血性卒中患者中的应用
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作者 霍礼功 王钰 +2 位作者 陈蓓蕾 于海龙 李军 《国际脑血管病杂志》 2019年第4期287-293,共7页
缺血性卒中的发生、发展和再灌注治疗过程中可能对血脑屏障结构和功能造成破坏,导致血脑屏障通透性增加,进而出现脑水肿或出血性转化,最终造成转归不良。目前已可对血脑屏障通透性进行定量评估。文章就血脑屏障通透性评估方法及其在缺... 缺血性卒中的发生、发展和再灌注治疗过程中可能对血脑屏障结构和功能造成破坏,导致血脑屏障通透性增加,进而出现脑水肿或出血性转化,最终造成转归不良。目前已可对血脑屏障通透性进行定量评估。文章就血脑屏障通透性评估方法及其在缺血性卒中患者中的应用进行了综述。 展开更多
关键词 卒中 脑缺血 血脑屏障 通透性 磁共振成像 体层摄影术 X线计算机
脑转移癌患者免疫组化与电镜特征及局部血脑屏障变化的临床意义 预览
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作者 汪逵 邓民强 +2 位作者 魏文 周晗 李元红 《实用癌症杂志》 2019年第5期707-709,713共4页
目的探讨脑转移癌患者免疫组化与电镜特征及局部血脑屏障变化的临床意义。方法选取16例脑转移癌患者的标本蜡块,同时随机选取16例同时期接受治疗的脑胶质瘤患者术后标本蜡块作为对照,对其做CD34、FV-Ⅲ、GFAP、S-100、NSE、NF、MBP和SY... 目的探讨脑转移癌患者免疫组化与电镜特征及局部血脑屏障变化的临床意义。方法选取16例脑转移癌患者的标本蜡块,同时随机选取16例同时期接受治疗的脑胶质瘤患者术后标本蜡块作为对照,对其做CD34、FV-Ⅲ、GFAP、S-100、NSE、NF、MBP和SYN染色,观察各标志物在2组中的表达情况。选取同期接受脑肿瘤手术切除的患者新鲜标本,其中,脑胶质瘤2例,脑转移癌4例,对其做电镜观察,了解血脑屏障连接的变化。结果脑转移癌组和脑胶质瘤组中,CD34和FV-Ⅲ均有丰富表达,其阳性数相比较,差异无统计学意义(P>0.05),在脑胶质瘤组织中,GFAP、S-100、NSE、NF、MBP和SYN均强烈表达,但是在脑转移癌组中,几乎不表达,提示脑转移癌中没有胶质膜成分,即没有形成血脑屏障的最基本的结构。电镜扫描表明,脑转移癌患者内皮细胞连结松紧不一,纤细疏松,部分间隙扩大,常见空泡变性,基膜不均一且较薄,与胶质瘤相比毛细血管密度略少,毛细血管周围无胶质细胞终足,瘤细胞之间出现淋巴细胞浸润。结论在脑转移癌组织中,构成血脑屏障的基本物质神经胶质膜缺乏,血管内皮连接不紧密,即其组织中无完整的血脑屏障。 展开更多
关键词 血脑屏障 免疫组化 电镜 脑转移癌
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聚焦超声在脑部疾病的应用进展 预览
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作者 李进丹 许泽艳 +2 位作者 王瑞 杨军 廖承德 《中国医学影像技术》 CSCD 北大核心 2019年第3期439-442,共4页
血脑屏障(BBB)阻碍多数治疗药物进入脑组织,导致临床诊治脑部疾病、特别是中枢神经系统疾病困难。借助微泡造影剂,聚焦超声可以无创、重复开放BBB。近年来国内外逐渐开展了聚焦超声治疗脑部疾病的实验和临床研究。本文就聚焦超声在脑部... 血脑屏障(BBB)阻碍多数治疗药物进入脑组织,导致临床诊治脑部疾病、特别是中枢神经系统疾病困难。借助微泡造影剂,聚焦超声可以无创、重复开放BBB。近年来国内外逐渐开展了聚焦超声治疗脑部疾病的实验和临床研究。本文就聚焦超声在脑部疾病的研究进展进行综述。 展开更多
关键词 血脑屏障 聚焦超声 脑部疾病
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新型小鼠脑爆震伤模型的建立及研究
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作者 佟昌慈 柳云恩 +6 位作者 张玉彪 丛培芳 施琳 史秀云 刘颖 侯明晓 金红旭 《中华急诊医学杂志》 CAS CSCD 北大核心 2019年第1期44-49,共6页
目的研发一种新型爆震伤模拟装置建立小鼠脑爆震伤模型,并研究小鼠脑爆震伤的损伤机制。方法30只昆明小鼠随机(随机数字法)分为正常对照组(Ctrl组)和脑爆震伤模型组(TBI组)。利用自主研发的爆震伤模拟装置制备脑爆震伤小鼠模型,并采用Mo... 目的研发一种新型爆震伤模拟装置建立小鼠脑爆震伤模型,并研究小鼠脑爆震伤的损伤机制。方法30只昆明小鼠随机(随机数字法)分为正常对照组(Ctrl组)和脑爆震伤模型组(TBI组)。利用自主研发的爆震伤模拟装置制备脑爆震伤小鼠模型,并采用Morris水迷宫、伊文思蓝(EB)实验和HE染色,观察小鼠脑部经冲击波暴露后空间记忆能力、血脑屏障、脑组织病理改变的影响。Western-blot方法检测脑损伤标志物Tau、S100β、胆碱,炎症相关因子IL-1β、IL-4、IL-6、IL-10、NF-κB,凋亡相关因子Bcl-2、Bax、Caspase3和氧化应激相关因子IREα、MDA5、COX2、SOD1和SOD2的蛋白表达。两组间计量资料比较采用成组t检验。结果与Ctrl组(11.2±2.1)s相比,TBI组小鼠寻找平台时间为(54.6±8.4)s,明显增加(t=-19.330,P<0.05);TBI组小鼠EB渗出量比Ctrl组明显增高3.22倍(t=-13.903,P<0.05);病理染色可见海马区神经元损伤,同时TBI诱导脑组织损伤标志物Tau(0.26±0.03vs0.46±0.04,t=-9.788,P<0.05)、S100β(0.54±0.03vs.0.74±0.02,t=-12.433,P<0.05)和胆碱(0.54±0.05vs0.80±0.04,t=-7.970,P<0.05),炎性因子IL-1β(0.22±0.04vs0.31±0.05,t=-3.431,P<0.05)、IL-4(0.65±0.02vs0.97±0.03,t=-18.927,P<0.05)、IL-6(0.88±0.05vs1.07±0.08,t=-9.488,P<0.05)和NF-κB(0.80±0.06vs1.03±0.07,t=-4.507,P<0.05),促凋亡因子Caspase-3(0.44±0.03vs0.60±0.05,t=-4.472,P<0.05)和Bax(0.66±0.04vs0.78±0.04,t=-13.007,P<0.05),促氧化因子IREα(0.72±0.06vs1.07±0.04,t=-9.665,P<0.05)、MDA5(0.47±0.02vs0.77±0.02,t=-23.678,P<0.05)和COX2(0.70±0.07vs0.86±0.02,t=-6.421,P<0.05)的蛋白表达,降低抑炎因子IL-10(1.14±0.06vs0.74±0.07,t=13.729,P<0.05)、抑凋亡因子Bcl-2(0.72±0.05vs0.46±0.02,t=11.491,P<0.05)及抑氧化应激因子SOD1(1.17±0.05vs0.99±0.01,t=7.731,P<0.05)和SOD2(0.81±0.05vs0.61±0.04,t=10.257,P<0.05)的蛋白表达。结论脑爆震伤可损伤小鼠空间学习记忆能力、破坏血脑屏障、损伤海马区神经元,同时促进脑损伤标志� 展开更多
关键词 脑爆震伤 模拟装置 空间记忆学习能力 血脑屏障 损伤
Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion 预览
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作者 Zuo-Yan Sun Fu-Jiang Wang +6 位作者 Hong Guo Lu Chen Li-Juan Chai Rui-Lin Li Li-Min Hu Hong Wang Shao-Xia Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第5期783-793,共11页
Shuxuetong injection composed of leech(Hirudo nipponica Whitman)and earthworm(Pheretima aspergillum)has been used for the clinical treatment of acute stroke for many years in China.However,the precise neuroprotective ... Shuxuetong injection composed of leech(Hirudo nipponica Whitman)and earthworm(Pheretima aspergillum)has been used for the clinical treatment of acute stroke for many years in China.However,the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood.Here,cerebral microvascular endothelial cells(bEnd.3)were incubated in glucose-free Dulbecco’s modified Eagle’s medium containing 95%N2/5%CO2 for 6 hours,followed by high-glucose medium containing 95%O2 and 5%CO2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model.This in vitro cell model was administered Shuxuetong injection at 1/32,1/64,and 1/128 concentrations(diluted 32-,64-,and 128-times).Cell Counting Kit-8 assay was used to evaluate cell viability.A fluorescence method was used to measure lactate dehydrogenase,and a fluorescence microplate reader used to detect intracellular reactive oxygen species.A fluorescent probe was also used to measure mitochondrial superoxide production.A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells.The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability.Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha,interleukin-1β,interleukin-6,and inducible nitric oxide synthase.Western blot assay was performed to analyze expression of caspase-3,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,occludin,vascular endothelial growth factor,cleaved caspase-3,B-cell lymphoma 2,phosphorylated extracellular signal-regulated protein kinase,extracellular signal-regulated protein kinase,nuclear factor-κB p65,I kappa B alpha,phosphorylated I kappa B alpha,I kappa B kinase,phosphorylated I kappa B kinase,claudin-5,and zonula occludens-1.Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression,reduces cleaved caspase-3 expression,inhibits produ 展开更多
关键词 nerve REGENERATION SHUXUETONG injection brain MICROVASCULAR endothelial cells oxygen-glucose deprivation/reperfusion tight junction proteins mitochondrial function inflammatory factors blood-brain barrier neuroprotection neural REGENERATION
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补阳还五汤对实验性自身免疫性脑脊髓炎小鼠血脑屏障保护作用的研究 预览
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作者 刘建春 张红珍 +5 位作者 郭文娟 柴智 尉杰忠 于婧文 肖保国 马存根 《山西中医学院学报》 2019年第1期20-25,共6页
目的:探讨补阳还五汤(BYHWD)对实验性自身免疫性脑脊髓炎(EAE)在发病潜伏期、高峰期和缓解期的血-脑屏障(BBB)保护的机制。方法:采用髓鞘MOG35-55诱导C57BL/6雌性小鼠建立EAE模型,随机分为EAE组和BYHWD组。于免疫后第3天开始灌胃给药,EA... 目的:探讨补阳还五汤(BYHWD)对实验性自身免疫性脑脊髓炎(EAE)在发病潜伏期、高峰期和缓解期的血-脑屏障(BBB)保护的机制。方法:采用髓鞘MOG35-55诱导C57BL/6雌性小鼠建立EAE模型,随机分为EAE组和BYHWD组。于免疫后第3天开始灌胃给药,EAE组给予生理盐水,BYHWD组给予BYHWD,在免疫后的第9天、第17天和第28天,分别采集小鼠脑和脊髓标本,行HE染色和固蓝染色;采用Western Blot法检测脊髓和脑内细胞紧密连接蛋白Occludin、ZO-1的表达。结果:补阳还五汤治疗后可抑制中枢神经系统炎细胞浸润,减轻髓鞘脱失;与EAE对照组比较,BYHWD治疗9 d、17 d和28 d,脊髓和脑内紧密连接蛋白Occludi和ZO-1表达增加。结论:补阳还五汤可以通过上调脊髓和脑内细胞紧密连接蛋白Occludin、ZO-1的表达,发挥血脑屏障(BBB)完整性的保护,从而发挥神经保护的作用。 展开更多
关键词 多发性硬化 补阳还五汤 血脑屏障 紧密连接蛋白
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CT灌注成像联合血脑屏障损伤标志物对脓毒症相关性脑病的诊断价值
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作者 周伶伶 梁瑞金 殷亮 《国际放射医学核医学杂志》 2019年第3期242-249,共8页
目的探讨CT灌注成像联合血脑屏障损伤标志物对脓毒症相关性脑病(SAE)的诊断价值。方法选取2015年7月至2017年10月收治的脓毒症患者84例[男性46例、女性38例,年龄19~76(54.05±13.70)岁]。将发生SAE作为观察组(38例),不发生SAE作为... 目的探讨CT灌注成像联合血脑屏障损伤标志物对脓毒症相关性脑病(SAE)的诊断价值。方法选取2015年7月至2017年10月收治的脓毒症患者84例[男性46例、女性38例,年龄19~76(54.05±13.70)岁]。将发生SAE作为观察组(38例),不发生SAE作为对照组(46例),分别于入院后第1、3天检测血清闭锁蛋白(Occludin)、一氧化氮合酶(NOS)、神经元特异性烯醇化酶(NSE)、中枢神经特异蛋白(S100β)、胶质纤维酸性蛋白(GFAP)和兴奋性氨基酸(EAA)的水平,并行脑部CT灌注成像,计算感兴趣区(ROI)的脑血流量(rCBF)、血容量(rCBV)、平均通过时间(rMTT),比较两组患者血清学指标及CT灌注成像结果。组间、组内比较均行t检验,Logistic回归分析SAE发生与各指标的相关性。采用受试者工作特征(ROC)曲线分析各变量单独及联合检测诊断脓毒症脑病的临床价值。结果观察组患者第1、3天rCBF分别为(45.63±16.56)、(34.83±15.64)mL·100g^-1·min^-1,分别低于对照组的(63.61±16.61)、(56.34±15.74)mL·100g^-1·min^-1,且差异有统计学意义(t=4.945、8.003,均P=0.000);第1、3天rCBV分别为(2.04±0.95)、(1.59±0.86)mL/100g,分别低于对照组的(2.53±1.04)、(2.06±1.04)mL/100g,差异有统计学意义(t=2.234、2.240,均P=0.028);第3天rMTT为(3.92±0.93)s,高于对照组的(3.43±1.04)s,且差异有统计学意义(t=2.254,P=0.027)。入院后第3天,观察组患者血清Occludin、NOS、NSE、S100β、GFAP、EAA水平分别为(128.37±15.61)ng/L、(56.04±10.54)U/mL、(23.03±4.96)mg/L、(0.39±0.05)μg/L、(125.39±37.83)ng/L、(5.88±2.63)μmol/L,分别高于对照组的(115.21±12.56)ng/L、(51.67±11.30)U/mL、(20.43±3.34)mg/L、(0.35±0.06)μg/L、(82.67±16.55)ng/L、(4.73±1.05)μmol/L,且差异均有统计学意义(t=4.282、2.379、2.858、5.732、10.351、2.718,P=0.000、0.020、0.005、0.000、0.000、0.008)。Logistic回归分析发现,SAE的发生与入院后第3天的rCBF(95%CI:0.629~1.006,r=-0.624,P=0.037)、rCBV(95%CI:0.010~1.174,r 展开更多
关键词 脓毒症 脓毒症相关性脑病 体层摄影术 X线计算机 灌注成像 血脑屏障
七十味珍珠丸对脑缺血再灌注损伤大鼠血脑屏障的保护作用 预览
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作者 梁源 孙位军 +4 位作者 王张 贾晓静 胥培艳 付珂 徐文龙 《中成药》 CAS CSCD 北大核心 2019年第4期767-773,共7页
目的考察七十味珍珠丸对脑缺血再灌注损伤大鼠血脑屏障的保护作用。方法线栓法建立大鼠脑缺血模型,2h后再灌注。72只大鼠随机分为假手术组、模型对照组、尼莫地平片组(30.00mg/kg)、七十味珍珠丸组(66.68mg/kg),每组再分为3个亚组(脑梗... 目的考察七十味珍珠丸对脑缺血再灌注损伤大鼠血脑屏障的保护作用。方法线栓法建立大鼠脑缺血模型,2h后再灌注。72只大鼠随机分为假手术组、模型对照组、尼莫地平片组(30.00mg/kg)、七十味珍珠丸组(66.68mg/kg),每组再分为3个亚组(脑梗死率、血脑屏障通透性、脑组织形态学),于脑缺血再灌注后2、24h观察神经行为学变化,24h检测脑梗死率、血清SOD活性和MDA水平、血脑屏障通透性、缺血侧脑组织病理变化和尼氏小体数。结果与模型对照组比较,七十味珍珠丸组显著降低大鼠脑梗死率(P<0.01)和缺血侧脑组织伊文思蓝(EB)含有量(P<0.05),显著改善神经行为学异常(P<0.01),显著增加尼氏小体数(P<0.05),脑组织病理变化、SOD活性、MDA水平有改善趋势,但无显著性差异(P>0.05)。结论七十味珍珠丸对脑缺血再灌注损伤大鼠脑组织有明显保护作用,其机制可能与抑制血脑屏障通透性增加有关。 展开更多
关键词 七十味珍珠丸 脑缺血再灌注损伤 血脑屏障
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PJ34对脑缺血再灌注大鼠应用rt-PA后血脑屏障完整性的影响
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作者 张玉鹏 李芳 +2 位作者 陈竹 毛鹤 王东玉 《中国临床解剖学杂志》 CSCD 北大核心 2019年第3期287-291,298共6页
目的研究多聚ADP核糖聚合酶-1(poly-ADP ribose polymerase-1,PARP-1)抑制剂PJ34能否改善脑缺血再灌注大鼠应用重组人组织型纤溶酶原激活物(recombinant tissue plasminogen activator,rtPA)后的血脑屏障完整性。方法将60只大鼠随机分... 目的研究多聚ADP核糖聚合酶-1(poly-ADP ribose polymerase-1,PARP-1)抑制剂PJ34能否改善脑缺血再灌注大鼠应用重组人组织型纤溶酶原激活物(recombinant tissue plasminogen activator,rtPA)后的血脑屏障完整性。方法将60只大鼠随机分为假手术组、缺血再灌注(ischemia-reperfusion,IR)组、rt-PA组及PJ34组。IR组:采用改良Zea Longa线栓法,制备局灶性脑缺血2 h再灌注模型。PJ34组及rt-PA组:缺血2 h拔出鱼线,同时给予尾静脉注射rt-PA 10 mg/kg,腹腔注射PJ34或生理盐水3 mg/kg。进行神经功能缺损评分、伊文氏蓝测定血脑屏障通透性、免疫组化分析MMP-9、Claudin-5、ZO-1的表达。结果 rt-PA组的神经功能缺损评分、伊文氏蓝含量及MMP-9表达均高于IR组,PJ34组低于rt-PA组,但高于IR组(P<0.05);rt-PA组的Claudin-5、ZO-1表达低于IR组,PJ34组高于rt-PA组,但低于IR组(P<0.05)。结论 PJ34通过抑制MMP-9的表达,增加Claudin-5、ZO-1的表达,可以有效改善脑缺血再灌注后应用rt-PA的大鼠血脑屏障完整性。 展开更多
关键词 PJ34 血脑屏障 缺血再灌注 重组人组织型纤溶酶原激活物
运动预处理对大鼠脑缺血再灌注损伤后血脑屏障通透性的影响 预览
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作者 梁碧莹 朱路文 +4 位作者 唐强 叶涛 李宏玉 李保龙 阮野 《中国康复理论与实践》 CSCD 北大核心 2019年第3期302-306,共5页
目的观察运动预处理对大鼠脑缺血再灌注损伤后血脑屏障通透性,以及连接蛋白43(Cx43)和泛连接蛋白1(Panx1)的影响。方法54只雄性Sprague-Dawley大鼠随机分为假手术组、模型组和运动预处理组,每组18只。造模前,运动预处理组行跑台训练3周... 目的观察运动预处理对大鼠脑缺血再灌注损伤后血脑屏障通透性,以及连接蛋白43(Cx43)和泛连接蛋白1(Panx1)的影响。方法54只雄性Sprague-Dawley大鼠随机分为假手术组、模型组和运动预处理组,每组18只。造模前,运动预处理组行跑台训练3周。采用改良Koizumi线栓法闭塞对模型组和运动预处理组大脑中动脉,再灌注24h后,采用改良神经功能缺损评分(mNSS)评估神经功能;伊文思蓝渗透法观察血脑屏障通透性;Westernblotting和免疫组化检测缺血侧脑组织Cx43和Panx1蛋白表达。结果与模型组比较,运动预处理组mNSS评分降低(P<0.05),伊文思蓝含量以及Cx43和Panx1蛋白表达量下降(P<0.05),Cx43和Panx1阳性面积率降低(P<0.05)。结论运功预处理可改善脑缺血再灌注大鼠血脑屏障通透性,下调Cx43蛋白和Panx1蛋白表达,具有脑保护作用。 展开更多
关键词 脑缺血再灌注损伤 运动预处理 血脑屏障 连接蛋白43 泛连接蛋白1 大鼠
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Magnesium:pathophysiological mechanisms and potential therapeutic roles in intracerebral hemorrhage 预览
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作者 Jason J.Chang Rocco Armonda +1 位作者 Nitin Goyal Adam S.Arthur 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第7期1116-1121,共6页
Intracerebral hemorrhage(ICH)remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expan... Intracerebral hemorrhage(ICH)remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies. 展开更多
关键词 INTRACEREBRAL HEMORRHAGE stroke magnesium VASODILATION HEMOSTASIS blood-brain barrier perihematomal EDEMA
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基于CiteSpace的国内外抗菌药物透过血脑屏障的研究进展及可视化分析 预览
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作者 范婷 杨树 赵志刚 《中国抗生素杂志》 CAS CSCD 2019年第7期868-875,共8页
目的利用科学文献可视化分析软件CiteSpace对国内外抗菌药物透过血脑屏障的研究现状、研究热点和发展趋势等进行客观全面的展示与分析,为临床用药提供有用的指导与参考。方法以Web of Science数据库、CNKI数据库为检索对象,纳入建库至... 目的利用科学文献可视化分析软件CiteSpace对国内外抗菌药物透过血脑屏障的研究现状、研究热点和发展趋势等进行客观全面的展示与分析,为临床用药提供有用的指导与参考。方法以Web of Science数据库、CNKI数据库为检索对象,纳入建库至今发表的与抗菌药物透过血脑屏障研究相关的文献,使用Excel对原始数据进行初步的文献计量分析,使用CiteSpace对关键词、作者、期刊、机构、国家等进行科学文献可视化分析,形成相关的可视化科学网络图谱。结果抗菌药物透过血脑屏障的研究主要集中在血脑屏障的结构与功能、中枢神经系统感染的预防与治疗、抗菌药物的PK/PD、新型抗菌药物、抗菌药物载体等方面,研究热度不断上升。美国、欧洲、日本都在抗菌药物透过血脑屏障研究方面有着突出的贡献,但是各国、各机构之间的合作交流并不密切。国内研究相比国外研究,存在起步时间晚、研究数量少、研究质量不高的缺陷,无论是发文量还是文章质量均落后于国外,需要加强与国际的合作交流与学习。结论目前,抗菌药物透过血脑屏障的研究日益受到人们的重视,欧美与日本对抗菌药物透过血脑屏障的研究处于世界领先水平。国内研究与国外仍存在很大差距,需要加大对抗菌药物透过血脑屏障研究的投入,促进临床合理用药。 展开更多
关键词 血脑屏障 抗菌药物 CITESPACE 可视化分析
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血脑屏障损伤诱发神经病变的评估方法及机制研究进展 预览
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作者 陈亦豪 吴昊 魏俊吉 《基础医学与临床》 CSCD 2019年第1期120-124,共5页
血脑屏障(BBB)是人体的生理屏障结构,发挥维持中枢神经系统内环境稳定的重要作用。中枢神经系统疾病如颅脑创伤、颅内肿瘤和神经退行性病变等均可以引起血脑屏障的损害。此外,血脑屏障损伤可以诱发中枢神经系统病变。目前,缺乏简明精确... 血脑屏障(BBB)是人体的生理屏障结构,发挥维持中枢神经系统内环境稳定的重要作用。中枢神经系统疾病如颅脑创伤、颅内肿瘤和神经退行性病变等均可以引起血脑屏障的损害。此外,血脑屏障损伤可以诱发中枢神经系统病变。目前,缺乏简明精确的血脑屏障评估手段成为中枢神经病变临床实践和研究的一个限制性因素。因此,血脑屏障评估技术及其完整性对中枢神经系统病变的意义十分重要。 展开更多
关键词 血脑屏障 中枢神经系统疾病 实验方法学
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缺血性脑卒中中药治疗进展
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作者 周文瑾 《中医学报》 CAS 2019年第1期60-65,共6页
中药及其活性成分通过减少炎症介质的释放,减轻白细胞浸润和保护血脑屏障,对脑缺血后的炎症反应进行干预发挥药理作用。中药单片及其有效成分能够直接透过血脑屏障,促进其他药物的渗透,同时在血脑屏障受损时降低其通透性,修复损伤,保护... 中药及其活性成分通过减少炎症介质的释放,减轻白细胞浸润和保护血脑屏障,对脑缺血后的炎症反应进行干预发挥药理作用。中药单片及其有效成分能够直接透过血脑屏障,促进其他药物的渗透,同时在血脑屏障受损时降低其通透性,修复损伤,保护脑组织。通过抑制缺血诱导的小胶质细胞激活和其介导的促炎细胞因子在缺血区产生微粒,生成促炎介质,增加黏附分子的表达;同时,中药可抑制血管瘤,改善缺血性脑卒中的神经功能损伤,调节转录因子NF-κB。中药对缺血性脑卒中具有良好的抗炎药效,但目前对于中药作用机制的阐述尚不明确,对炎症作用的靶点研究不足,对中药主要有效成分的研究较为片面,今后需进一步加强运用生物技术研究中药的化学成分,明确其活性成分,阐明中药对缺血性脑卒中介导炎症反应的精确机制。 展开更多
关键词 缺血性脑卒中 血脑屏障 炎症因子 小胶质细胞
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