星形胶质细胞在脑缺血中的双重作用

星形胶质细胞是中枢神经系统中数量最多的神经细胞,发挥着重要的生理作用.在脑缺血过程中,星形胶质细胞活化是中枢神经系统的主要变化之一.活化的星形胶质细胞可通过维持离子平衡、调节能量代谢、清除兴奋性氨基酸、对抗氧化应激、分泌神经保护物质等机制发挥神经保护作用.然而,脑缺血后星形胶质细胞活化也有其不利的一面.文章对星形胶质细胞活化在脑缺血中的保护与损害作用进行了综述,探讨了其调控机制,旨在为缺血性卒中的治疗提供新的思路.     

星形细胞及胶质纤维酸性蛋白在脑梗死中的作用

文章从神经营养因子与星形细胞的关系、星形细胞活性的分布与卒中后星形细胞活性及脑梗死后电刺激的相关研究进行了综述 ,阐述了星形细胞及胶质纤维酸性蛋白在脑梗死中的作用。     

星形细胞及胶质纤维酸性蛋白在脑梗死中的作用

文章从神经营养因子与星形细胞的关系、星形细胞活性的分布与卒中后星形细胞活性及脑梗死后电刺激的相关研究进行了综述,阐述了星形细胞及胶质纤维酸性蛋白在脑梗死中的作用。     

胶质淋巴系统与缺血性卒中后脑水肿

胶质淋巴系统是近年来发现的脑内液体转运和物质清除系统。它通过血管周围间隙和星形胶质细胞上的水通道蛋白4, 促进脑脊液与间质液流动交换, 清除代谢废物, 维持大脑内部环境稳定。脑水肿是由脑组织内液体积聚过多所致。最近的研究显示, 胶质淋巴系统在脑内液体的摄入和排出过程中起着重要作用, 胶质淋巴系统的改变可能是缺血性卒中后发生脑水肿的重要原因。文章就胶质淋巴系统在缺血性卒中后脑水肿形成过程中的病理生理学机制及相关治疗靶点进行了综述, 以期为缺血性卒中后脑水肿的治疗提供新思路。     

小胶质细胞吞噬在急性缺血性卒中中的作用

小胶质细胞作为脑内固有的免疫细胞,是中枢神经系统损伤的重要防线,参与了缺血性卒中的发病过程。特别是小胶质细胞的吞噬功能,在缺血性卒中的发病过程中具有重要作用。文章综述了小胶质细胞在急性缺血性卒中中的重要作用和吞噬机制,着重探讨其吞噬功能对卒中后神经损伤和恢复的双重影响,期望为小胶质细胞靶向的急性缺血性卒中治疗提供新的靶...     

TREM2对小胶质细胞的免疫调控在缺血性卒中中的作用

缺血性卒中是一种常见的神经系统疾病, 可导致神经元死亡和神经功能障碍。小胶质细胞是中枢神经系统的主要免疫细胞, 参与卒中后炎症和组织修复。髓样细胞表达的触发受体2(triggering receptor expressed on myeloid cells 2, TREM2)是一种在小胶质细胞表面表达的受体, 在缺血性卒中后神经元存活和神经修复方面发挥着多方面的作用, 包括促进小胶质细胞的吞噬作用、抑制过度的炎症反应、维持小胶质细胞的增殖和存活、保护神经元免受损伤以及促进神经功能恢复。因此, 阐明脑缺血后TREM2对小胶质细胞的免疫调节机制, 对于探索缺血性卒中新的治疗方向具有重要意义。     

缺血性卒中的神经保护药:现状与挑战

作为缺血性卒中的一种治疗策略,神经保护药被用于拮抗脑缺血时的一系列有害分子生物学事件.文章综述了神经保护药治疗急性缺血性卒中的现状,以及从临床前研究证据向临床试验转化所面临的挑战.应将血管内皮细胞-胶质细胞-神经元作为一个整体进行研究.     

大鼠脊髓来源神经干细胞分化的星形胶质细胞亚型观察

目的观察大鼠脊髓来源神经干细胞分化形成星形胶质细胞的亚型。方法用悬浮培养法培养大鼠脊髓来源的神经干细胞,形成神经球后,以免疫荧光法鉴定神经干细胞;胶质纤维酸性蛋白(GFAP)抗体标记星形胶质细胞,观察其星形胶质细胞的亚型。结果神经干细胞分化第7天,观察到星形胶质细胞共有4种亚型,其中胞体延长型占2.39%±0.13%,扁平多角形占32.33%±2.01%,星形占59.88%±3.12%,双极型占5.39%±0.27%。结论大鼠脊髓来源神经干细胞分化成的星形胶质细胞具有多样性,以星形、扁平多角形为主。     

新生儿缺氧缺血性脑病临床症状与神经病理的研究

通过对25例新生儿缺氧缺血性脑病(HIE)病理标本进行组织病理研究,并通过免疫组化观察胶质原纤维性酸性蛋白(GFAP)标记的星形胶质细胞的变化.结果 25例新生儿HIE脑标本均存在不同程度的脑水肿、颅内出血及神经细胞坏变.所有标本均可见星形胶质细胞增生,小脑增生程度表现为生后24 h内死亡者增生程度重,生存时间越长,增生程度反而较轻;慢性缺氧大脑星形胶质细胞增生程度重,急性缺氧延髓增生程度重,混合性缺氧大脑及延髓增生程度均较重.认为新生儿HIE神经病理变化与HIE的发生、病程、围产儿的成熟度密切相关.     

缺血性卒中后小胶质细胞介导的炎性信号通路

小胶质细胞是中枢神经系统最主要的免疫细胞,在介导中枢神经系统免疫应答中起着关键作用.在缺血性卒中后的病理学过程中,无菌性炎症是关键因素.通过损伤相关配体与相应受体结合,小胶质细胞激活并诱导一系列炎性信号.文章从Toll样受体、炎性小体、细胞因子受体、Notch信号以及其他信号通路介绍缺血性卒中后小胶质细胞的激活和炎性反应.     

RhoA/ROCK signaling pathway and astrocytes in ischemic stroke

Ischemic stroke is one of the most common and undertreated cerebral diseases with high mortality and disability rate. Various intrinsic and extrinsic factors regulate the onset, severity, and progression of ischemic stroke. As an integral part of the neuronal glia system, astrocytes provide many housekeeping functions in nervous system, and perform multiple functions both beneficial and detrimental for neuronal survival after ischemic stroke. In addition, the small GTPase Rho and its downstream Rho kinase (ROCK) are associated with various neuronal functions such as dendrite development, migration and axonal extension, and numerous central nervous system (CNS) diseases. The aim of this review is to summarize the role of RhoA/ROCK signaling pathway and astrocytes on neurological function after ischemic stroke. We also discuss the interaction of RhoA/ROCK signaling pathway and astrocytes on the tissue repair after brain injury.

     

The role of mineralocorticoid receptor expression in brain remodeling after cerebral ischemia

Mineralocorticoid receptors (MRs) are classically known to be expressed in the distal collecting duct of the kidney. Recently it was reported that MR is identified in the heart and vasculature. Although MR expression is also found in the brain, it is restricted to the hippocampus and cerebral cortex under normal condition, and the role played by MRs in brain remodeling after cerebral ischemia remains unclear. In the present study, we used the mouse 20-min middle cerebral artery occlusion model to examine the time course of MR expression and activity in the ischemic brain. We found that MR-positive cells remarkably increased in the ischemic striatum, in which MR expression is not observed under normal conditions, during the acute and, especially, subacute phases after stroke and that the majority of MR-expressing cells were astrocytes that migrated to the ischemic core. Treatment with the MR antagonist spironolactone markedly suppressed superoxide production within the infarct area during this period. Quantitative real-time RT-PCR revealed that spironolactone stimulated the expression of neuroprotective or angiogenic factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), whereas immunohistochemical analysis showed astrocytes to be cells expressing bFGF and VEGF. Thereby the incidence of apoptosis was reduced. The up-regulated bFGF and VEGF expression also appeared to promote endogenous angiogenesis and blood flow within the infarct area and to increase the number of neuroblasts migrating toward the ischemic striatum. By these beneficial effects, the infarct volume was significantly reduced in spironolactone-treated mice. Spironolactone may thus provide therapeutic neuroprotective effects in the ischemic brain after stroke.     

Cancer‐associated ischemic stroke is associated with elevated d‐dimer and fibrin degradation product levels in acute ischemic stroke with advanced cancer

Aim: Although several studies have reported various causes of ischemic stroke in patients with cancer, only a few have evaluated the clinical relevance of ischemic stroke pathogenesis to cancer. The aim of the present study was to elucidate the clinical characteristics of cancer‐associated ischemic stroke. Methods: We evaluated 154 ischemic stroke patients without cancer and 57 ischemic stroke patients with cancer who had either received continuous treatment for cancer within 5 years before to the onset of ischemic stroke, or who had been diagnosed with cancer within 1 year after the onset of ischemic stroke. Cancer patients were grouped into “cancer‐associated ischemic stroke,” the “conventional ischemic stroke,” or “other.” Results: A total of 15 patients (26%) were classified into the cancer‐associated ischemic stroke in cancer patients. In univariate analysis of the cancer‐associated ischemic stroke and the others, there were significant differences in the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d ‐dimer, fibrin degradation product and hemoglobin. With multivariate regression analysis of those factors, the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d ‐dimer and fibrin degradation product remained as statistically independent factors, which were associated with cancer‐associated ischemic stroke (n = 111, χ² = 67.21, P < 0.0001). Conclusion: In acute ischemic stroke, the cancer‐associated ischemic stroke is associated with elevated d ‐dimer and fibrin degradation products, even after controlling hypertension, hyperlipidemia and advanced cancer (clinical stage IV). Geriatr Gerontol Int 2012; 12: 468–474.     

骨髓单个核细胞移植在脑梗死小鼠脑内分化为星形胶质样细胞的研究

目的探讨骨髓单个核细胞(BMMNC)移植对大脑中动脉栓塞小鼠的治疗作用以及脑内分化情况。方法选择41只雄性昆明小鼠,采用线栓法制备大脑中动脉栓塞模型后,将制模成功的34只小鼠随机分为溶剂组和BMMNC移植组(移植组),每组17只。分别于模型成功后1、3、7、14和28d采用改良神经功能缺损评分(mNSS)评价小鼠神经损害严重程度,免疫荧光双标法观测BMMNC脑内分化情况。结果与溶剂组比较,移植组1、3、7、14和28d各时间点mNSS明显降低[(12.54±1.50)分vs(13.02±1.52)分、(9.52±1.25)分vs(11.17±1.05)分、(7.92±1.24)分vs(10.75±1.06)分、(5.82±1.23)分vs(7.93±1.23)分、(4.92±1.25)分vs(6.83±1.12)分,P<0.05];移植组梗死皮质及海马齿状回区5-溴脱氧尿嘧啶核苷和胶质纤维酸性蛋白双标阳性细胞。结论BMMNC移植在脑梗死小鼠脑内分化为星形胶质样细胞,能显著改善脑梗死小鼠神经功能。     

高血压伴与不伴缺血性脑卒中患者颈动脉内中膜厚度的研究

目的 :用彩色多普勒超声观察高血压伴与不伴缺血性脑卒中患者颈动脉内中膜厚度 ,探讨颈动脉粥样硬化与缺血性脑卒中的关系。方法 :用HDI 30 0 0彩色多普勒超声观察了 36例无缺血性脑卒中的高血压病患者和 36例伴有缺血性脑卒中的高血压病患者双侧颈动脉内中膜厚度 ,并与 2 8名健康对照进行了比较。结果 :1 3组间空腹血糖、血脂和体重指数及平均年龄无显著性差异 (P >0 0 5 ) ;2 单纯高血压病患者和高血压病伴缺血性脑卒中患者颈动脉内中膜厚度明显高于健康对照者 (P <0 0 1) ,且高血压伴缺血性脑卒中患者颈动脉内中膜厚度明显高于无缺血性脑卒中的高血压患者 (P <0 0 1)。结论 :高血压病患者存在有颈动脉粥样硬化 ,且伴有缺血性脑卒中患者颈动脉粥样硬化程度明显加重 ,提示颈动脉粥样硬化程度可作为预测缺血性脑卒中发生的参考指标。     

急性缺血性卒中合并心脏病患者血压管理专家共识

急性缺血性卒中的血压管理不同于陈旧缺血性卒中的血压管理。当急性缺血性卒中合并心脏病(如急性心肌梗死或心力衰竭等)时,对于血压管理的要求就变得更加复杂。本共识围绕急性缺血性卒中合并急慢性冠状动脉综合征、合并心力衰竭等临床复杂情况,对降压时机、降压目标、降压用药及处置流程等进行专家意见的总结。     

缺血性脑卒中患者健康素养及影响因素的研究

目的了解缺血性脑卒中患者健康素养现状及影响因素,为预防和改善缺血性脑卒中患者预后开展健康促进工作提供科学依据。方法采用便利抽样法选取两所医院200例缺血性脑卒中住院患者进行健康素养问卷调查。结果①研究对象健康素养总均分(139.32±36.21)分,处于临界水平。②年龄、文化程度、婚姻状态是缺血性脑卒中患者健康素养的影响因素。结论缺血性脑卒中患者健康素养处于临界水平,且受年龄、文化程度、婚姻状态因素的影响,提升健康素养有利于提高脑卒中二级预防的防治水平,从而改善缺血性脑卒中患者的健康结局。     

吸烟与男性缺血性脑卒中患者大脑中动脉狭窄的关联性分析

目的探讨吸烟与男性大脑中动脉狭窄及缺血性脑卒中患者发病年龄的关系。方法连续收集广东省人民医院收住院的缺血性脑卒中并行全脑数字减影血管造影术检查的男性患者257例,根据是否吸烟分为吸烟组140例和非吸烟组117例,对比2组患者大脑中动脉M1段狭窄率及发病年龄。结果吸烟组大脑中动脉M1段狭窄发生率显著高于非吸烟组(49.3%vs 24.8%),发生缺血性脑卒中的年龄明显小于非吸烟组[(60.13±10.52)岁vs(65.26±11.77)岁,P<0.01]。吸烟组年龄≤60岁缺血性脑卒中发生率明显高于非吸烟组(50.7%vs 27.4%,P<0.01)。结论吸烟可能是男性患者大脑中动脉M1段狭窄的一个重要危险因素,且吸烟可能使男性患者更早发生缺血性脑卒中。     

北京市急性缺血性脑卒中磁共振成像分型研究

目的研究北京市急性脑梗死磁共振显示的亚型分布情况,使北京市急性缺血性脑卒中患者得到更加准确的病因学和个体化治疗。方法回顾分析北京市东城、西城、朝阳、海淀等4个区6家医院2004年接诊的647例急性缺血性脑卒中的分型情况及影像学特征。结果北京市五家医院急性脑梗死的亚型构成为:腔隙性脑梗死46.5%,小梗死38.1%,中梗死9.4%,大梗死6.0%。结论北京市急性脑梗死的分布以腔隙性脑梗死为多发,提示小动脉病变是北京市缺血性脑卒中的最主要病理改变。根据影像学的分型法可用于急性缺血性脑卒中的早期分型、指导治疗、评估预后。     

Role of astrocytes in estrogen-mediated neuroprotection

Recent work has suggested that the ovarian steroid hormone, 17beta-estradiol (E2), at physiological concentrations, may exert protective effects in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and acute ischemic stroke. While physiological concentrations of E2 have consistently been shown to be protective in vivo, direct protection of neurons remains controversial, suggesting that while direct protection of neurons may occur in some instances, an alternative or parallel pathway for protection may exist which could involve another cell type in the brain. In the present review, we summarize the data in support of a possible role for astrocytes in the mediation of neuroprotection by E2. We also summarize the data suggesting a non-classical estrogen receptor may underlie some of the protective effects of E2 by activating cellular signaling pathways, such as extracellular-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt. A possible indirect pathway involving astrocytes may act in concert with the proposed direct pathway to achieve a widespread, global protection of both ER positive and negative neurons.