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Neuroprotective mechanism of TMP269, a selective class ⅡA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury 预览
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作者 Lu Su Dan Liang +3 位作者 Shen-Yi Kuang Qiang Dong Xiang Han Zheng Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期277-284,共8页
TMP269 is a selective class ⅡA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of ... TMP269 is a selective class ⅡA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of TMP269 for protecting against cerebral ischemia/reperfusion injury and its neuroprotective mechanism. Male Sprague-Dawley rats were randomly divided into sham, ischemia/reperfusion, and 1, 4, 10 and 16 mg/kg TMP269 groups. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. TMP269 was intraperitoneally administered at different doses 0.5 hours before ischemia induction. Western blot assay and immunohistochemistry were used to detect effects of TMP269 on histone 2 acetylation. The results showed that the level of histone 2 acetylation was increased 24 hours after TMP269 injection. 2,3,5-Triphenyltetrazolium chloride staining was utilized to examine effect of TMP269 on infarct volume. The results found that different doses of TMP269 could reduce the infarct volume. Western blot assay, immunohistochemistry and Evans blue staining were employed to measure the effect of TMP269 on blood-brain barrier. The results showed that TMP269 counteracted the abnormal endothelial cell permeability changes caused by cerebral ischemia/reperfusion. Western blot assay and immunohistochemistry were used to determine the effect of TMP269 on tissue kallikrein. The results found that TMP269 up-regulated the expression of tissue kallikrein. Western blot assay further determined the optimal concentration to be 4 mg/kg. In conclusion, TMP269 plays a neuroprotective role by up-regulating the level of histone 2 acetylation, alleviating endothelial cell injury after cerebral ischemia/reperfusion, and up-regulating the expression of tissue kallikrein. The experimental protocol was approved in 2014 by the Department of Laboratory Animal Science, Fudan University, China(approval No. 20140143 C001). 展开更多
关键词 blood-brain barrier drug treatment endothelial cell permeability HISTONE DEACETYLASE inhibitor NEUROPROTECTION stroke tissue KALLIKREIN TMP269
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血脑屏障体外模型的研究进展(综述) 预览
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作者 徐麟 胡凯莉 《安徽卫生职业技术学院学报》 2019年第5期91-93,95共4页
血脑屏障(BBB)是位于中枢神经系统(CNS)和中枢系统环境间的一层生理保护屏障。对于治疗脑部疾病的药物来说,需要先通过BBB才能起效。BBB体外模型则是研究药物的BBB透过性或评价脑靶向纳米粒的脑部递药特性的有效工具。近年来,体外BBB模... 血脑屏障(BBB)是位于中枢神经系统(CNS)和中枢系统环境间的一层生理保护屏障。对于治疗脑部疾病的药物来说,需要先通过BBB才能起效。BBB体外模型则是研究药物的BBB透过性或评价脑靶向纳米粒的脑部递药特性的有效工具。近年来,体外BBB模型的应用日趋广泛并在脑部疾病相关研究中发挥着重要作用。该文综述了国内外体外血脑屏障模型的发展现状及其在应用方面的最新研究进展。 展开更多
关键词 血脑屏障 体外血脑屏障模型 纳米粒 中枢神经系统
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脑靶向肽修饰的BDNF对阿尔茨海默症小鼠的神经保护作用 预览
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作者 柯莉 方登富 +1 位作者 潘飞豹 赵磊 《西部医学》 2019年第10期1543-1548,共6页
目的探讨脑靶向肽修饰的脑源性神经营养因子(BDNF)对阿尔茨海默症小鼠的神经保护作用。方法使用基因工程的方法将一段脑靶向肽(TGN)与BDNF连接,诱导表达获取重组蛋白(TGN-BDNF),聚丙烯酰胺凝胶电泳(SDS-PAGE)和蛋白质免疫印迹(WB)鉴定... 目的探讨脑靶向肽修饰的脑源性神经营养因子(BDNF)对阿尔茨海默症小鼠的神经保护作用。方法使用基因工程的方法将一段脑靶向肽(TGN)与BDNF连接,诱导表达获取重组蛋白(TGN-BDNF),聚丙烯酰胺凝胶电泳(SDS-PAGE)和蛋白质免疫印迹(WB)鉴定重组蛋白。将重组蛋白腹腔注射至APP/PS1双转基因小鼠,酶联免疫吸附试验(Elisa)检测脑组织中BDNF的含量。实验分为4组:对照组、模型组、BDNF组、TGN-BDNF组,Morris水迷宫试验测定小鼠的空间学习记忆能力,Elisa检测海马中Aβ、Tau蛋白和乙酰胆碱的含量,WB检测TrkB/Erk/CREB信号通路的表达。结果 BDNF和TGN-BDNF的分子质量分别为15.79kd和17.10kd,经SDS-PAGE与WB鉴定正确。与模型组和BDNF组相比较,TGN-BDNF组脑组织中BDNF的含量在注射后30min、1h和3h时升高(P<0.05),在注射后6h时无统计学差别(P>0.05)。与模型组和BDNF组相比较,TGN-BDNF组小鼠第5d的潜伏期下降,穿台次数上升(P<0.05);海马中Aβ和Tau蛋白含量下降,乙酰胆碱含量上升(P<0.05);海马中p-TrkB、p-Erk和p-CREB的表达升高(P<0.05)。结论脑靶向肽修饰的BDNF具有良好的脑靶向性,能够改善阿尔茨海默症小鼠的空间学习记忆能力,降低海马Aβ和Tau蛋白含量,增加乙酰胆碱含量,促进TrkB/Erk/CREB信号通路的活化,为阿尔茨海默症的治疗提供了新的思路。 展开更多
关键词 靶向肽 脑源性神经营养因子 阿尔茨海默症 血脑屏障
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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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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 Bloodbrain barrier 10-HYDROXYCAMPTOTHECIN
炎症在慢性脑低灌注引起的认知损害中的作用及其机制
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作者 彭茜 胡杨 +2 位作者 王倩 邹文颖 陈卓友 《国际脑血管病杂志》 2019年第6期467-470,共4页
慢性脑低灌注(chronic cerebral hypoperfusion, CCH)是中枢神经系统疾病共有的病理改变,与认知损害密切相关。多项研究表明,炎症参与了CCH引起的认知损害的发病和进展过程。在CCH状态下,脑内炎症反应的激活可导致多种病理损伤,如白质... 慢性脑低灌注(chronic cerebral hypoperfusion, CCH)是中枢神经系统疾病共有的病理改变,与认知损害密切相关。多项研究表明,炎症参与了CCH引起的认知损害的发病和进展过程。在CCH状态下,脑内炎症反应的激活可导致多种病理损伤,如白质病变、血脑屏障破坏、海马神经元变性坏死等。因此,抑制炎症反应有望为CCH引起的认知损害提供新的治疗靶点。文章就炎症在CCH引起的认知损害中的作用机制进行综述。 展开更多
关键词 脑缺血 认知障碍 炎症 白质 血脑屏障
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
毛蕊异黄酮对大鼠蛛网膜下腔出血后血脑屏障和氧化应激反应的影响
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作者 常江 余华 +1 位作者 张晓乐 李俊玲 《吉林中医药》 2019年第10期1347-1350,共4页
目的探讨毛蕊异黄酮对蛛网膜下腔出血脑水肿和神经炎症反应的影响。方法体质量230~250 g的雄性SD大鼠72只,随机分为4组:假手术对照组(Sham组)、蛛网膜下腔出血组(SAH组)、毛蕊异黄酮15(C1组)、30 mg/(kg·d)组(C2组)。采用血管内穿... 目的探讨毛蕊异黄酮对蛛网膜下腔出血脑水肿和神经炎症反应的影响。方法体质量230~250 g的雄性SD大鼠72只,随机分为4组:假手术对照组(Sham组)、蛛网膜下腔出血组(SAH组)、毛蕊异黄酮15(C1组)、30 mg/(kg·d)组(C2组)。采用血管内穿刺法建立大鼠蛛网膜下腔出血(SAH)模型。Sham组仅在手术操作中将尼龙线头端送至右颈内动脉,但不刺破动脉管壁;SAH组大鼠制备SAH模型;C1组和C2组大鼠分别每日口饲毛蕊异黄酮溶液(溶于无菌生理盐水)15或30 mg/kg共7 d,之后制备SAH模型。术后24 h行脑水含量检测和伊文思蓝染色以分别反映脑水肿和血脑屏障破坏程度;采用超氧化物歧化酶(SOD)和丙二醛(MDA)试剂盒分别检测脑SOD活性和MDA摩尔浓度。结果与Sham组比较,SAH组大鼠脑水含量和伊文思蓝外渗率均明显增加(P <0.05),SOD活性显著降低(P <0.05),MDA摩尔浓度明显增加(P <0.05);与SAH组比较,C1和C2组大鼠脑水含量和伊文思蓝外渗率均明显减少(P <0.05),SOD活性显著增加(P <0.05),MDA摩尔浓度下调(P <0.05)。结论毛蕊异黄酮预处理可缓解蛛网膜下腔出血后脑水肿和血脑屏障破坏,减轻神经炎症反应和细胞凋亡,其机制可能与激活Nrf2信号通路相关。 展开更多
关键词 毛蕊异黄酮 蛛网膜下腔出血 血脑屏障 氧化应激反应 脑水肿
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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低压低氧大鼠脱适应期血脑屏障通透性和脑微血管密度的变化 预览
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作者 罗强 刘卫平 +4 位作者 龙乾发 张胡金 柴源 苗宇 伊西才 《山西医科大学学报》 CAS 2019年第11期1561-1564,共4页
目的探讨实验性低压低氧大鼠在脱适应期血脑屏障(BBB)通透性和脑微血管密度(MVD)的变化。方法雄性SD大鼠72只随机分为低压低氧模型组和对照组,将模型组大鼠置于模拟海拔4 000 m的高原环境模拟舱内,氧浓度12. 6%,连续暴露4周后让其重返... 目的探讨实验性低压低氧大鼠在脱适应期血脑屏障(BBB)通透性和脑微血管密度(MVD)的变化。方法雄性SD大鼠72只随机分为低压低氧模型组和对照组,将模型组大鼠置于模拟海拔4 000 m的高原环境模拟舱内,氧浓度12. 6%,连续暴露4周后让其重返常氧环境,按照返回常氧环境不同时间点再随机分成5个亚组(n=12,重返常氧环境后第1,3,7,14,30天),分别检测BBB通透性和脑MVD,BBB检测采用伊文氏蓝(EB)示踪法结合脑组织EB含量测定,MVD采用免疫组化法检测脑组织CD34+细胞的表达。结果与对照组相比,低压低氧模型组大鼠脑组织EB含量明显增加(P <0. 01),随着返回常氧环境时间的延长而逐渐呈降低的趋势,与返回常氧环境时间呈显著负相关(r=-0. 898,P=0. 038);与BBB通透性变化一致,模型组大鼠脑组织CD34+细胞数明显增多(P <0. 01),与返回常氧环境时间呈显著负相关(r=-0. 883,P=0. 016)。结论低压低氧大鼠在脱适应期BBB通透性和脑MVD发生了明显的变化,高原脱适应反应的发生可能与其改变有关。 展开更多
关键词 低压低氧 血脑屏障 脑微血管密度 高原脱适应反应 高原缺氧
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外泌体与缺血性卒中
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作者 刘品一 徐运 曹翔 《国际脑血管病杂志》 2019年第8期620-623,共4页
外泌体是细胞外囊泡中的一种,内含丰富的蛋白质、RNA、脂质等,具有来源和靶向的特异性,同时能透过血脑屏障,可作为疾病的生物标志物以及药物载体。近年来的研究显示,外泌体在缺血性卒中的病理生理学过程中发挥重要作用。脑缺血时,内皮... 外泌体是细胞外囊泡中的一种,内含丰富的蛋白质、RNA、脂质等,具有来源和靶向的特异性,同时能透过血脑屏障,可作为疾病的生物标志物以及药物载体。近年来的研究显示,外泌体在缺血性卒中的病理生理学过程中发挥重要作用。脑缺血时,内皮细胞来源的外泌体可造成血脑屏障破坏,而星形胶质细胞及少突胶质细胞分泌的外泌体则具有神经保护功能。间充质干细胞的外泌体经工程改造能促进卒中后神经修复,改善神经功能缺损。文章就外泌体与缺血性卒中相关性的研究进展进行了综述。 展开更多
关键词 卒中 脑缺血 外泌体 血脑屏障
健脾益气利水方对脑缺血大鼠脑水肿及其脑组织Occludin、Claudin-1、ZO-1蛋白表达的影响
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作者 李花 胡康丽 +4 位作者 刘旺华 何倩 戴思思 唐冰镕 杨程 《中华中医药杂志》 CAS CSCD 北大核心 2019年第11期5424-5428,共5页
目的:探讨健脾益气利水方(JPF)对脑缺血大鼠脑水肿及脑组织紧密连接蛋白闭合蛋白(Occludin)、密封蛋白-1(Claudin-1)、闭锁连接蛋白-1(ZO-1)表达的影响。方法:将105只雄性SD大鼠随机分为假手术组,模型组,依达拉奉组,JPF小、中、大剂量... 目的:探讨健脾益气利水方(JPF)对脑缺血大鼠脑水肿及脑组织紧密连接蛋白闭合蛋白(Occludin)、密封蛋白-1(Claudin-1)、闭锁连接蛋白-1(ZO-1)表达的影响。方法:将105只雄性SD大鼠随机分为假手术组,模型组,依达拉奉组,JPF小、中、大剂量组。采用线栓法制备大脑中动脉栓塞(MCAO)模型,治疗7d后处死,运用伊文思蓝(EB)渗出法检测血脑屏障的通透性,运用免疫组化法检测大鼠缺血侧脑组织Occludin、Claudin-1、ZO-1蛋白表达。结果:与假手术组比较,模型组缺血侧脑组织EB的含量显著增加(P<0.01),Occludin、Claudin-1、ZO-1阳性细胞表达显著降低(P<0.01);与模型组比较,依达拉奉组和JPF中、大剂量组大鼠缺血侧脑组织EB的含量明显降低(P<0.05),各给药组Occludin、Claudin-1、ZO-1阳性细胞表达明显增强(P<0.01,P<0.05)。结论:健脾益气利水法组方可能通过上调紧密连接蛋白Occludin、Claudin-1、ZO-1表达保护血脑屏障,减轻脑缺血再灌注大鼠脑水肿。 展开更多
关键词 脑缺血 脑水肿 血脑屏障 健脾益气利水法 闭合蛋白 密封蛋白-1 闭锁连接蛋白-1
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