癫痫大鼠海马神经元和星形胶质细胞的病理演变

目的　探讨癫痫大鼠海马神经元和星形胶质细胞在点燃后各期的病理特点、时序及机制。方法　针对匹罗卡品癫痫大鼠模型,行Nissl、免疫组化和HE染色,观察海马神经元及星形胶质细胞的病理变化。结果　癫痫持续状态后超急性期（4h）,CA3区神经元呈嗜酸性变性、胞浆深染;急性期（24h）,嗜酸性变性最为显著,神经元固缩、核仁消失、突起断裂,星形胶质细胞水肿;缄默期（7d）,CA3、CA1区及门区神经元大量坏死、脱失,胶质增生肥大,海马构筑紊乱;慢性期（6w）,CA3、CA1区出现胶质瘢痕,遗有形态正常的神经元,且颗粒细胞层增厚。结论　癫痫时海马神经元先于星形胶质细胞发生病理改变,二者均参与癫痫发生。     

人脑梗死后神经元与星形胶质细胞细胞骨架蛋白的改变

急性脑梗死后的病理生理机制包括细胞骨架蛋白的降解、细胞凋亡的发生、胶质细胞的反应和微循环损害等。其中 ,细胞骨架蛋白维持真核细胞的空间结构 ,包括微管、微丝或肌动蛋白丝以及中间丝 3种类型 ,参与细胞内物质转运、细胞运动、信息传递、能量转换、细胞分裂等活动 [1 ] 。其变化反映了神经细胞的存活和功能状态 ,可提示梗死后不同区域的功能状态 [2 ]。1　细胞骨架概述细胞骨架 (cytoskeleton)是由蛋白纤维交织成的立体网状结构 ,如同一种内部框架 ,充满整个细胞质的空间 ,与外侧的细胞膜和内侧的核膜存在一定的结构联系 [3]。由 3种…     

星形胶质细胞、胶质纤维酸性蛋白和抑郁症的关系

对胶质细胞、胶质纤维酸性蛋白在心境障碍神经病理学发病机制中的作用进行综述。     

中枢神经系统中星形胶质细胞活化机制的研究进展

星形胶质细胞在中枢神经系统(CNS)中含量丰富,对神经元起着支持、营养、修复等多种重要作用.在CNS损伤或外源性物质作用时,星形胶质细胞发生活化.JAK-STAT3、核因子κB(NF-κB)、丝裂原活化蛋白激酶(MAPK)、TGF-β/Smad等多条信号通路共同作用,调节星形胶质细胞内相应基因的转录与表达.探究星形胶质...     

胶质纤维酸性蛋白在老年痴呆大鼠海马中的表达

为探讨慢性缺血痴呆鼠学习减退与海马内星形胶质细胞表达的关系,基于老年大鼠慢性脑缺血痴呆模型,采用免疫组化技术及迷宫实验,定量分析海马星形胶质细胞变化与学习能力、记忆能力的关系。结果发现,慢性缺血痴呆鼠海马CAl区GFAP阳性细胞数目明显增多,胞体肥大,突起增粗、变长,与对照组相比有显著意义(P<0.05),Y型迷宫测试结果显示,痴呆组大鼠的学习、记忆能力与对照组相比,明显下降。提示海马星形胶质细胞可能参与慢性缺血痴呆大鼠的学习记忆功能。     

PS激发大鼠延髓内脏带星形胶质细胞GFAP和神经元FOS表达水平的变化

观察腹腔注射细菌内毒素 (LPS)后 ,大鼠延髓内脏带 (MVZ)星形胶质细胞胶质原纤维酸性蛋白 (GFAP)及神经元FOS表达水平随时间变化的规律及其相互关系。大鼠经LPS腹腔注射后 1,3,6,12h分别行固定取材制片。每个时间点的切片分为 3组 ,分别进行抗FOS、抗GFAP免疫组织化学染色及抗FOS/GFAP/酪氨酸羟化酶 (TH)三重免疫组织化学染色。结果表明 :①FOS反应在LPS注射后 3h达到高峰 ,阳性产物主要分布于MVZ内。②GFAP反应在注射后 1h即达到高峰 ,表现为胶质细胞肥大、数量增多。其分布与FOS基本相同。③三重染色观察到GFAP与FOS的多种聚集方式 (FOS/GFAP/TH ,FOS/GFAP ,GFAP/TH) ,FOS阳性神经元周围GFAP免疫反应产物更密集。提示星形胶质细胞对LPS起反应 ,其反应高峰的出现先于神经元     

星形胶质细胞主要细胞骨架研究的最新进展

星形胶质细胞(Astrocyte,Ast)是中枢神经系统的主要细胞成分之一,约占正常成人中枢神经系统细胞总数的40％,其功能日益受到重视.其细胞骨架主要由微丝(MF)、微管(MT)和中间纤维(IFs)3种蛋白质组成,其细胞骨架的复杂变化在中枢神经系统的生理和病理变化中发挥重要作用,本文就生理病理条件下Ast细胞骨架的复杂变化(细胞骨架的生物学特性、信号转导途径、细胞骨架的构建与其在临床疾病中变化等)作一综述.     

星形胶质细胞在脑出血后脑水肿中作用的研究

目的　观察星形细胞在脑出血急性期周围脑组织中的作用。方法　获取 30例脑出血患者出血灶周围脑组织标本 ,根据脑出血时间分为三组 ,超早期 (<8小时 ) ,8例 :早期 (8～ 4 8小时 ) ,16例 ;延期(>4 8小时 ) ,6例。应用胶质纤维酸性蛋白 (GFAP)进行免疫组织化学染色 ,观察其表达程度。结果　随着脑出血后时间的延长 ,GFAP染色灰度值越低 ,说明星形细胞增生越明显。结论　星形胶质细胞参与脑水肿的病理过程 ,并对组织修复可能具有重要作用。     

脑脊膜持续强化的自身免疫性胶质纤维酸性蛋白星形胶质细胞病一例

<正>自身免疫性胶质纤维酸性蛋白(glial fibrillary acidic protein, GFAP)星形胶质细胞病是以脑膜、脑、脊髓和视神经等受累为主要表现的自身免疫性疾病,多对糖皮质激素(下文简称“激素”)治疗敏感。GFAP抗体,也称为GFAP免疫球蛋白G(GFAP-IgG),被认为是本病的特异性生物标志物。本文报道1例起病5个多月后影像学仍可见脑膜脊膜强化的自身免疫性GFAP星形胶质细胞病,此情况临床较为罕见。     

大鼠脑缺血再灌注后星形胶质细胞反应性变化差异与海马CA1区的迟发性神经元死亡

BACKGROUND： Blood supply to the hippocampus is not provided by the middle cerebral artery. However, previous studies have shown that delayed neuronal death in the hippocampus may occur following focal cerebral ischemia induced by middle cerebral artery occlusion.
OBJECTIVE： To observe the relationship between reactive changes in hippocampal astrocytes and delayed neuronal death in the hippocampal CA1 region following middle cerebral artery occlusion.
DESIGN, TIME AND SETTING： The immunohistochemical, randomized, controlled animal study was performed at the Laboratory of Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from July to November 2007.
MATERIALS： Rabbit anti-glial fibrillary acidic protein （GFAP） （Neomarkers, USA）, goat anti-rabbit IgG （Sigma, USA） and ApoAlert apoptosis detection kit （Biosciences Clontech, USA） were used in this study. METHODS： A total of 42 healthy adult male Wistar rats, aged 3–5 months, were randomly divided into a sham operation group （n = 6） and a cerebral ischemia/reperfusion group （n = 36）. In the cerebral ischemia/reperfusion group, cerebral ischemia/reperfusion models were created by middle cerebral artery occlusion. In the sham operation group, the thread was only inserted into the initial region of the internal carotid artery, and middle cerebral artery occlusion was not induced. Rats in the cerebral ischemia/reperfusion group were assigned to a delayed neuronal death （＋） subgroup and a delayed neuronal death （–） subgroup, according to the occurrence of delayed neuronal death in the ischemic side of the hippocampal CA1 region following cerebral ischemia.
MAIN OUTCOME MEASURES： Delayed neuronal death in the hippocampal CA1 region was measured by Nissl staining. GFAP expression and delayed neuronal death changes were measured in the rat hippocampal CA1 region at the ischemic hemisphere by double staining for GFAP and TUNEL.
RESULTS： After 3 days of ischemia/reperfusion, astrocytes with abnormal morphology were detected in the rat hippocampal CA1 region in the delayed neuronal death （＋） subgroup. No significant difference in GFAP expression was found in the rat hippocampal CA1 region at the ischemic hemisphere in the sham operation group, delayed neuronal death （＋） subgroup and delayed neuronal death （–） subgroup （P 〉 0.05）. After 7 days of ischemia/reperfusion, many GFAP-positive cells, which possessed a large cell body and an increased number of processes, were activated in the rat hippocampal CA1 region at the ischemic hemisphere. GFAP expression in the hippocampal CA1 region was greater in the delayed neuronal death （＋） subgroup and delayed neuronal death （–） subgroup compared with the sham operation group （P 〈 0.01）. Moreover, GFAP expression was significantly greater in the delayed neuronal death （–） subgroup than in the delayed neuronal death （＋） subgroup （P 〈 0.01）. After 30 days of ischemia/reperfusion, GFAP-positive cells were present in scar-like structures in the rat hippocampal CA1 region at the ischemic hemisphere. GFAP expression was significantly greater in the delayed neuronal death （＋） subgroup and delayed neuronal death （–） subgroup compared with the sham operation group （P 〈 0.05）. GFAP expression was significantly lower in the delayed neuronal death （–） subgroup than in the delayed neuronal death （＋） subgroup （P 〈 0.05）. The delayed neuronal death rates were 42% （5/12）, 33% （4/12） and 33% （4/12） at 3, 7 and 30 days, respectively, followingischemia/reperfusion. No significant differences were detected at various time points （χ2 = 0.341, P 〉 0.05）.
CONCLUSION： The activation of astrocytes was poor in the hippocampal CA1 region during the early stages of ischemia, which is an important reason for delayed neuronal death. Glial scar formation aggravated delayed neuronal death during the advanced ischemic stage.     

锂-匹罗卡品致大鼠癫癎持续状态后脑内神经元的凋亡

探讨癫持续状态 (StatusEpilepticus,SE)时细胞凋亡的发生及其与海马硬化的关系。采用锂 匹罗卡品诱发大鼠SE模型 ,在SE的不同时点采大鼠脑标本 ,利用TUNEL染色方法检测大鼠海马皮质神经元的凋亡出现情况。结果发现 ,正常对照组大鼠大脑皮质可见散在的TUNEL阳性细胞 ,海马区未见TUNEL阳性细胞。SE1h ,皮质TUNEL阳性细胞数即开始增加 ,SE后 8h ,海马区开始出现TUNEL阳性细胞 ,SE后 1d ,大脑皮质TUNEL阳性细胞数开始明显增加 ,海马区也可见到较多TUNEL阳性细胞。SE后 5d ,皮质及海马的TUNEL阳性细胞数达到高峰。 7d时皮质及海马TUNEL阳性数均明显下降。结果提示 ,SE可引起神经元凋亡 ,5d时达到高峰 ,7d时已明显下降。神经元凋亡与SE引起的迟发性神经元死亡有关 ,并参与了海马硬化的形成。     

Expression of estrogen receptor α and β in reactive astrocytes at the male rat hippocampus after status epilepticus

Estrogen is neuroprotective against status epilepticus (SE)‐induced hippocampal damage in female animals. In male animals, estrogen is converted from testosterone via aromatization the activity of which is upregulated by brain damage. However, it is controversial whether estrogen is neuroprotective or neuroinvasive against male hippocampal damage after SE. In order to understand the role of estrogen, it is important to elucidate the distribution manner of estrogen receptor (ER)α and β as the targets of estrogen. In this study, we examined the time course changes of ERs in adult male rat hippocampus after SE using anti‐ERα antibodies (MC‐20 and PA1‐309) and anti‐ERβ antibodies (PA1‐310B and PA1‐311). In control rats, both ERα and β were expressed in the pyramidal cells predominantly at CA1 and CA3. ERα was expressed in the cytoplasm and the nucleus, whereas ERβ was expressed in the cytoplasm of the pyramidal cells. After SE, according to the pyramidal cell loss at CA1, the number of ERα‐ and β‐immunoreactive pyramidal cells decreased up to day 21. On the other hand, reactive astrocytes, which newly appeared after SE and formed gliosis at CA1, were confirmed to express both ERs in the nucleus, cytoplasm, and process. There were no differences in immunoreactivity between antibodies. Our results indicate that endogenous estrogen affects the pyramidal cells through ERα and β under normal circumstances in adult male rats, whereas the targets of estrogen shift to the reactive astrocytes through ERα and β after SE.     

海藻氨酸致癫痫状态大鼠海马区神经元损伤与Mg^2＋作用的研究

目的观察海藻氨酸(KA)诱导的癫癎状态(SE)大鼠海马神经元的形态学改变和Mg2+的神经保护作用.方法选用成年雄性Wistar大鼠75只,随机分为KA组、Mg2+组和生理盐水对照组.用KA诱导大鼠SE 3 h,Mg2+组大鼠在注射KA前腹腔内注射硫酸镁100 mg/kg,在癫癎发作终止后72 h将动物处死,分别用光镜和电镜观察海马神经元形态学改变.结果 KA组大鼠注射KA后(16.1±4.7)min出现癫癎发作,Mg2+组大鼠为(25.4±6.2)min,两组比较差异有显著性(P<0.05).KA组和Mg2+组大鼠在海马区均出现了嗜酸性神经元,Mg2+组大鼠神经元损伤程度明显低于KA组.结论 KA诱导的SE可导致海马神经元坏死,而 Mg2+作为兴奋性氨基酸拮抗剂对海马神经元具有保护作用.     

Effects of status epilepticus on extracellular amino acids in the hippocampus

Extracellular amino acids were followed in the hippocampus during sustained seizures induced by systemic administration of kainic acid (KA) or bicuculline (BC). KA epilepsy was associated with marked increases in phosphoethanolamine (PEA) and taurine. Alanine and ethanolamine were moderately raised while other amino acids were unaffected. BC seizures encompassed a slightly different pattern of alterations. In contrast to KA seizures, BC epilepsy had no effect on taurine. Significant increments were observed for PEA and alanine while elevations of ethanolamine were subtle. In both types of seizures, glutamate and GABA remained unaffected extracellularly, probably due to efficient recapture mechanisms.     

Glutamate receptor 1-immunopositive neurons in the gliotic CA1 area of the mouse hippocampus after pilocarpine-induced status epilepticus

Significant reduction in glutamate receptor 1 (GluR1)- and GluR2/3-immunopositive neurons was demonstrated in the hilus of the dentate gyrus in mice killed on days 1, 7 and 60 after pilocarpine-induced status epilepticus (PISE). In addition, GluR1 and GluR2/3 immunostaining in the strata oriens, radiatum and lacunosum moleculare of areas CA1-3 decreased drastically on days 7 and 60 after PISE. Neuronal loss observed in the above regions may account, at least in part, for a decrease in GluR immunoreactivity. By contrast, many GluR1-immunopositive neurons were observed in the gliotic area of CA1. Of these, about 42.8% were immunopositive for markers for hippocampal interneurons, namely calretinin (7.6%), calbindin (12.8%) and parvalbumin (22.4%). GluR1 or GluR2/3 and BrdU double-labelling showed that the GluR1- and GluR2/3-immunopositive neurons at 60 days after PISE were neurons that had survived rather than newly generated neurons. Furthermore, anterograde tracer and double-labelling studies performed on animals at 60 days after PISE indicated a projection from the hilus of the dentate gyrus to gliotic areas in both CA3 and CA1, where the projecting fibres apparently established connections with GluR1-immunopositive neurons. The projection to CA1 was unexpected. These novel findings suggest that the intrinsic hippocampal neuronal network is altered after PISE. We speculate that GluR1-immunopositive neurons in gliotic CA1 act as a bridge between dentate gyrus and subiculum contributing towards epileptogenesis.     

Nestin expression in reactive astrocytes following focal cerebral ischemia in rats

During central nervous system (CNS) development, intermediate filaments are subjected to a sequential remodelling process. Nestin is a distinct intermediate filament which is transiently expressed in proliferating neuroepithelial stem cells during the neurulation stage of development. Nestin re-expression in the adult rat was studied following transient (2 h) middle cerebral artery occlusion. Seven days after the ischemic insult, nestin reactive astrocytes were found in the border zone surrounding cerebral infarction. Nestin immunoreactivity delineated a zone between infarction and the surrounding intact cerebral parenchyma. In situ hybridization for nestin mRNA showed early changes in small cells in the surround of the ischemic lesion. These results with nestin, along with other stem cell markers expressed by reactive astrocytes, suggest an embryonic reversion of the mature cytoskeleton as a response of astrocytes to cerebral injury.     

醒脑静注射液辅助静脉用丙戊酸钠治疗癫(癎)持续状态效果观察

目的:探讨醒脑静注射液配合丙戊酸钠治疗癫(癎)持续状态的疗效.方法:选择我院2013年8月～2016年1月收治的癫(癎)持续状态患者74例为研究对象,以随机数字表法分组,观察组37例,对照组37例,对照组单用丙戊酸钠治疗,观察组采取醒脑静注射液辅助静脉用丙戊酸钠治疗,对两组患者疗效进行观察.结果:观察组总有效率为92％,对照组为81％,两组比较差异有统计学意义(P＜0.05);观察组起效时间及完全控制时间均较对照组短,两组比较差异有统计学意义(P＜0.05);观察组复发率与不良反应发生率分别为8％和11％,对照组分别为11％和21％,两组比较差异均有统计学意义(P＜0.05).结论:醒脑静注射液辅助静脉用丙戊酸钠治疗癫(癎)持续状态效果显著,此两药具有相互协同作用,可快速起效,安全性高,利于远期预后.     

脑炎后癫痫持续状态进展为难治性癫痫持续状态及超级难治性癫痫持续状态的早期预测因素

目的 探讨脑炎后癫痫持续状态(SE)进展为难治性SE(RSE)及超级RSE(SRSE)的早期预测因素.方法 根据疾病进展情况将89例脑炎后SE患者分为非RSE组、RSE组及SRSE组.比较各组临床资料.结果 非RSE组、RSE组及SRSE组年龄、SE严重程度评分量表(STESS)评分、基于流行病学SE病死率评分(EMS...     

An MRI and neuropathological study of a case of fatal status epilepticus

We report a case of fatal status epilepticus of unknown origin resulting in acute neuropathological changes in the hippocampus and claustrum.The case history, brain magnetic resonance images, and results of neuropathological study of the whole brain were obtained.The subject was a 35 year old male with no significant previous medical history who presented with generalized epileptic seizures progressing to status epilepticus. He died 6 days after developing status epilepticus. Magnetic resonance imaging (MRI) brain scans were performed before and four days after developing status epilepticus. The first scan was normal and the second showed high signal lesions on T2 weighted images in the medial aspects of both temporal lobes and in the right claustrum. Neuropathological studies showed severe neuronal loss in the Sommer section of both hippocampi with early glial reactive changes. Similar changes were seen in the claustrum on both sides. There was no evidence of other causes of brain injury such as infectious encephalitis or global hypoxic-ischaemic change.The patient died of status epilepticus for which no underlying cause was found despite extensive investigation. In this case the radiological and pathological changes found bilaterally in the claustrum and hippocampus appear to be the direct result of the status epilepticus.