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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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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
补阳还五汤联合骨髓间充质干细胞对脑缺血大鼠血脑屏障通透性的影响
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作者 张运克 车志英 李可 《中华中医药学刊》 CAS 北大核心 2019年第7期1548-1553,共6页
目的:为了研究补阳还五汤联合骨髓间充质干细胞(MSCs)对脑缺血再灌注大鼠血脑屏障(blood brain barrier, BBB)通透性及其影响因素AQP4的表达。方法:将大鼠80只随机分为假手术组、模型组、补阳还五汤组、MSCs组、补阳还五汤联合MSCs组(... 目的:为了研究补阳还五汤联合骨髓间充质干细胞(MSCs)对脑缺血再灌注大鼠血脑屏障(blood brain barrier, BBB)通透性及其影响因素AQP4的表达。方法:将大鼠80只随机分为假手术组、模型组、补阳还五汤组、MSCs组、补阳还五汤联合MSCs组(联合组),每组各16只。利用改良线栓法制备大脑中动脉栓塞(middle cerebral artery obstruction,MCAO)缺血再灌注大鼠模型,在3、5 d运用干湿重法测定缺血脑组织含水量,采用伊文思蓝(Evans blue, EB)法检测血脑屏障的通透性,用透射电镜观察血脑屏障超微结构的变化,采用Western Blot法检测缺血脑组织中AQP4的表达。结果:与假手术组相比,在造模后3、5 d时间点,MCAO模型组大鼠脑组织含水量、EB含量显著升高,AQP4的蛋白表达水平上升,具有极显著性统计学意义(P<0.01);与模型组相比,补阳还五汤组、MSCs组、联合组中缺血脑组织含水量、EB含量及AQP4的蛋白表达水平显著下降,各组间有显著统计学意义(P<0.05)。联合组的作用在第5天更为明显,与MSCs组及补阳还五汤组相比,具有显著性差异(P<0.05)。结论:补阳还五汤联合MSCs可以降低脑组织的含水量及血脑屏障的通透性,维持BBB结构的完整性,其作用机制与水通道蛋白AQP4的调控密切相关。 展开更多
关键词 补阳还五汤 骨髓间充质干细胞 大脑中动脉栓塞(MCAO) 血脑屏障 脑组织含水量 AQP4蛋白
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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p115RhoGEF/RhoA信号通路在高糖致脑微血管内皮细胞通透性异常中的作用
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作者 蔡倩 郭慕真 +1 位作者 朱晨笛 黄敏 《营养学报》 CAS CSCD 北大核心 2019年第2期154-162,共9页
目的探讨p115RhoGEF/RhoA信号通路在高浓度葡萄糖(Glucose)致小鼠脑微血管内皮细胞(bEnd.3通透性异常中的作用。方法体外培养小鼠脑微血管内皮细胞(bEnd.3),构建单层血脑屏障体外模型。通过ESR电阻仪测定跨内皮细胞间电阻(TEER),分光光... 目的探讨p115RhoGEF/RhoA信号通路在高浓度葡萄糖(Glucose)致小鼠脑微血管内皮细胞(bEnd.3通透性异常中的作用。方法体外培养小鼠脑微血管内皮细胞(bEnd.3),构建单层血脑屏障体外模型。通过ESR电阻仪测定跨内皮细胞间电阻(TEER),分光光度法检测碱性磷酸酶(ALP)、γ-谷胺酞胺转移酶(γ-GT)活性以评估其屏障功能;对照组(5.6mmol/L葡萄糖)、高糖诱导组(15.6、25.6、35.6、45.6mmol/L葡萄糖)处理细胞48h,MTT检测细胞相对存活率,分光光度法检测培养上清中乳酸脱氢酶(LDH)活性,免疫印迹法(Western blot)检测紧密连接蛋白ZO-1、Occludin表达水平,评估高糖对脑微血管内皮细胞通透性的影响;Western blot检测不同浓度葡萄糖处理细胞后p115RhoGEF蛋白表达水平,体外蛋白与蛋白结合试验(Pull-Down)检测RhoA活性。转染p115RhoGEF-siRNA建立p115RhoGEF基因沉默的bEnd.3细胞模型,检测不同处理组RhoA活性及p115RhoGEF、TJ蛋白表达水平。结果细胞TEER值随培养时间延长逐渐升高,ALP、γ-GT活力均随时间延长逐渐升高;与对照组比较,35.6、45.6mmo/L葡萄糖诱导组的细胞活力出现明显下降作用,且诱导时间越长,细胞存活率越低(P<0.05);35.6mmol/L葡萄糖诱导组的LDH水平明显升高(P<0.05);随着葡萄糖浓度升高,ZO-1、Occludin蛋白表达下降而p115RhoGEF蛋白表达升高,差异有统计学意义(P<0.05);Pull-down结果显示,25.6、35.6mmol/L葡萄糖组的RhoA活性较对照组明显升高(P<0.05)。细胞转染p115RhoGEF-siRNA后,p115RhoGEF蛋白表达较对照组明显下降;高糖诱导48h后,与NCsiRNA组比较,p115RhoGEF-siRNA组的GTP-RhoA活性下降、 ZO-1、 Occludin表达水平明显上调(P<0.05)。结论高糖通过诱导p115RhoGEF/RhoA信号通路活化,下调紧密连接蛋白表达,引起脑微血管内皮细胞通透性增加。 展开更多
关键词 糖尿病血管病变 血脑屏障 脑微血管内皮细胞 P115RhoGEF/RhoA信号通路
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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纳米级脑靶向递药系统的靶向性提升策略
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作者 黄梦瑶 杨旭 +1 位作者 邢金峰 魏振平 《药学学报》 CAS CSCD 北大核心 2019年第4期629-637,共9页
血脑屏障能选择性阻滞外周血液中的物质进入脑内,这对于维持脑内环境稳定十分重要,但同时会阻碍治疗药物向脑内递送。被动脑靶向递药系统可以通过增强与血脑屏障细胞的亲和力及减弱P-糖基蛋白对药物的外排来提高脑内药物浓度;在被动靶... 血脑屏障能选择性阻滞外周血液中的物质进入脑内,这对于维持脑内环境稳定十分重要,但同时会阻碍治疗药物向脑内递送。被动脑靶向递药系统可以通过增强与血脑屏障细胞的亲和力及减弱P-糖基蛋白对药物的外排来提高脑内药物浓度;在被动靶向递药系统上结合特异性配体或抗体得到的主动脑靶向递药系统,能更精准地实现药物向脑内靶向递送;脑靶向联合肿瘤细胞靶向得到的双级靶向递药系统,对脑部肿瘤的治疗已显示出其独特优势。脑靶向递药系统将为阿尔茨海默病、脑肿瘤及中风等脑部疾病的治疗提供一种独特方式。在介绍被动型、主动型脑靶向及双级脑靶向递药系统的同时,本文重点对降低载体粒径、打开血脑屏障细胞间的紧密连接、于载体表面键合亲水性基团及鼻腔给药等提高药物脑内递送效率的策略进行了展望。 展开更多
关键词 血脑屏障 纳米级 递药系统 双级脑靶向 靶向性提升策略
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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整合素β1在缺血再灌注脑损伤中作用的研究进展
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作者 王婷 文国强 《中国临床神经科学》 2019年第2期223-228,共6页
缺血性脑卒中是一类常见的危害人类健康的疾病,目前明确的治疗措施有限。整合素β1是介导细胞与细胞之间、细胞与细胞外基质成分之间的黏附分子。已有研究发现整合素β1能促进缺血再灌注脑损伤的神经功能恢复,其作用主要为稳定血脑屏障... 缺血性脑卒中是一类常见的危害人类健康的疾病,目前明确的治疗措施有限。整合素β1是介导细胞与细胞之间、细胞与细胞外基质成分之间的黏附分子。已有研究发现整合素β1能促进缺血再灌注脑损伤的神经功能恢复,其作用主要为稳定血脑屏障、促进血管再生、调节细胞凋亡及神经元修复等病理生理过程。该发现为缺血性脑卒中的治疗提供新思路,可能成为治疗缺血性脑卒中的新靶点之一。文中就整合素β1的分子结构、分布及在缺血性脑损伤中的作用等研究进行综述,使业内研究者能够系统完整了解整合素β1治疗缺血性脑损伤中的作用机制。 展开更多
关键词 整合素Β1 缺血再灌注脑损伤 血脑屏障 血管新生 神经功能 细胞凋亡
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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非抗凝肝素衍生物ROH对脓毒症小鼠脑损伤的保护作用及机制研究
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作者 张嘉茜 赵晓禹 +1 位作者 梁洋 崔慧斐 《中国临床药理学杂志》 CAS CSCD 北大核心 2019年第13期1352-1355,共4页
目的研究非抗凝肝素衍生物--ROH对脂多糖(LPS)诱导的脓毒症小鼠脑损伤的保护作用及机制。方法按数表法将Balb/c小鼠随机分为4组:正常组、模型组、对照组和实验组。小鼠腹腔注射LPS 10 mg·kg^-1建立脓毒症急性脑损伤模型。对照组和... 目的研究非抗凝肝素衍生物--ROH对脂多糖(LPS)诱导的脓毒症小鼠脑损伤的保护作用及机制。方法按数表法将Balb/c小鼠随机分为4组:正常组、模型组、对照组和实验组。小鼠腹腔注射LPS 10 mg·kg^-1建立脓毒症急性脑损伤模型。对照组和实验组在造模前15 min,分别尾静脉注射肝素2. 5mg·kg^-1、ROH 7. 5 mg·kg^-1进行干预,正常组注射等体积0. 9%Na Cl。以免疫组化法检测脑组织乙酰肝素酶(HPA)和金属基质蛋白酶-9(MMP-9)表达水平;伊文思蓝染色法检测血脑屏障通透性;TBA法测定脑组织中丙二醛(MDA)的含量。结果正常组、模型组、对照组和实验组的HPA表达水平(光密度值)分别为(8. 0±8. 0)×10^-5,(3. 0±1. 8)×10^-3,(2. 3±1. 1)×10^-4和(5. 4±3. 3)×10^-4;上述这4组的MMP-9表达水平(光密度值)分别为(8. 0±8. 0)×10^-5,(3. 6±1. 8)×10^-3,(3. 9±1. 4)×10^-4和(4. 9±3. 3)×10^-4;上述这4组的脑内伊文思蓝的含量分别为(4. 36±1. 58),(78. 60±14. 75),(36. 28±9. 16)和(44. 09±8. 95)μg·g^-1;上述这4组的MDA含量分别为(6. 91±1. 73),(10. 88±2. 08),(6. 68±1. 58)和(5. 41±1. 50)nmol·mL^-1。模型组与正常组相比,上述指标的差异均有统计学意义(P <0. 05,P <0. 01);对照组和实验组与模型组相比,上述指标的差异均有统计学意义(P <0. 05,P <0. 01)。结论 ROH与肝素一样,通过抑制脓毒症时LPS所致的HPA和MMP-9高表达,保护内皮糖萼的完整性,从而发挥脑保护作用,并提高脓毒症小鼠的生存率。 展开更多
关键词 脓毒症 血脑屏障 内皮糖萼 非抗凝肝素
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
兔脑脊液中万古霉素LC-MS/MS测定方法的建立及其与冰片合用的药动学研究
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作者 李旭梅 褚正民 涂厉标 《中国现代应用药学》 CAS CSCD 北大核心 2019年第3期281-285,共5页
目的建立一种快速灵敏的LC-MS/MS用于兔脑脊液中万古霉素的测定,并进行万古霉素的药动学研究。方法观察兔分别单独静脉注射万古霉素以及先灌胃给予冰片再静脉注射给予万古霉素后脑脊液中万古霉素的浓度变化。采用内标法进行定量分析,获... 目的建立一种快速灵敏的LC-MS/MS用于兔脑脊液中万古霉素的测定,并进行万古霉素的药动学研究。方法观察兔分别单独静脉注射万古霉素以及先灌胃给予冰片再静脉注射给予万古霉素后脑脊液中万古霉素的浓度变化。采用内标法进行定量分析,获得脑脊液中万古霉素的浓度,并采用DAS药动学软件拟合主要动力学参数AUC、Cmax、T1/2等。结果脑脊液中万古霉素的批间精密度为4.7%~6.1%,批内精密度为1.4%~7.1%,准确度为93.6%~106.0%。万古霉素的线性范围为50~5 000 ng·mL-1,标准曲线的相关系数r>0.99。合用冰片组兔脑脊液中万古霉素的AUC和Cmax值明显高于单用万古霉素组。结论该方法适用于万古霉素在兔脑脊液中的药动学研究。冰片可以提高万古霉素透过血脑屏障的能力。 展开更多
关键词 万古霉素 冰片 血脑屏障 药动学
低频脉冲磁场对大鼠海马血脑屏障通透性的影响
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作者 陈琴 高鹏 +2 位作者 胡俊锋 丁桂荣 郭国祯 《中华放射医学与防护杂志》 CAS CSCD 北大核心 2019年第6期401-407,共7页
目的探讨不同磁场强度脉冲磁辐射对Sprague-Dawley大鼠海马组织血脑屏障(blood brain barrier, BBB)通透性的影响。方法选取72只成年雄性SD大鼠,完全随机分组法分为假暴露对照组、阳性对照组(肾上腺素,100 μg/kg)和4个不同磁场强度处理... 目的探讨不同磁场强度脉冲磁辐射对Sprague-Dawley大鼠海马组织血脑屏障(blood brain barrier, BBB)通透性的影响。方法选取72只成年雄性SD大鼠,完全随机分组法分为假暴露对照组、阳性对照组(肾上腺素,100 μg/kg)和4个不同磁场强度处理组(100、400、800、1 200 mT,每组脉冲次数为30个)。动物辐射后3 h取材,采用HE染色观察海马组织形态学结构;免疫组织化学法检测大鼠海马组织内微血管周围白蛋白渗出;伊文斯蓝(Evans blue, EB)荧光法观察微血管周围EB渗出情况;Western blot法检测脉冲磁场辐射后BBB紧密连接(tight junction,TJ)相关蛋白ZO-1和Occludin的表达变化。结果与假暴露对照组相比,不同磁场强度脉冲磁辐射组大鼠大脑海马组织结构无明显变化,脑微血管周围未见白蛋白和EB明显渗出,ZO-1蛋白水平在1 200 mT暴露组与假暴露对照组相比显著降低(t=14.26,P<0.05),Occludin蛋白水平及其他磁场强度暴露组的ZO-1水平未见明显变化(P>0.05)。结论低频脉冲磁场暴露对白蛋白通过BBB的通透性无明显影响,但是ZO-1蛋白水平的降低提示BBB完整性受到损伤。 展开更多
关键词 脉冲磁场 大鼠 海马组织 血脑屏障 紧密连接蛋白
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