大鼠脑缺血再灌注后胰岛素样生长因子－1的表达及意义

目的 观察胰岛素样生长因子-1（IGF-1）在大鼠脑缺血再灌注后在缺血不同部位的表达及组织病理学改变，探讨其对神经元的保护作用。方法 72只清洁级、成年健康雄性SD大鼠随机等分为假手术对照（sham）组和脑缺血再灌注（CIR）组，CIR组缺血3 h后，按再灌注时间的长短不同分为0、6、24、48、72 h和7 d 6个亚组，每亚组均为6只大鼠。于各相应时间点以Longa法、Berderson法和平衡木法分别进行行为学评分后处死动物，制做脑组织病理切片，苏木精-伊红染色后观察组织病理学改变，采用免疫组织化学方法测定IGF-1的动态表达变化。结果 （1）大鼠在大脑中动脉阻断后手术对侧肢体存在不同程度瘫痪，24 h后行为学评分结果逐渐趋于稳定,根据观察大鼠病变对侧肢体出现不同程度的瘫痪，其功能异常程度与病变严重程度一致；（2）除假手术对照（sham）组外，其余各组在脑梗死后6 h局部可见少量散在炎性细胞浸润，梗死后48 h炎性细胞浸润明显增多，并持续到7 d；（3）IGF-1在sham组神经元中呈弱阳性表达（灰度值127±6）；CIR组各缺血时段IGF-1表达分别为147±5（0 h）、153±6（6 h）、170±7（24 h）、169±5（48 h）、150±6（72 h）和147±5（7 d）。其中，缺血3 h及缺血3 h再灌注6 h组中心区、半影区阳性细胞数均增多，表达增强；随再灌注时间延长，中心区表达接近正常水平，半影区阳性细胞数增多，表达呈持续升高趋势，再灌注24 h和48 h达高峰，72 h表达有所下降，但仍表达高水平。结论 高表达的IGF-1参与了脑缺血再灌注后内源性神经保护过程，IGF-1在缺血半影区与中心区的演变病理生理中起重要作用，说明IGF-1对缺血半影区的保护作用。     

胰岛素样生长因子-1对大鼠脑缺血再灌注损伤的作用机制研究

目的观察尾静脉注射胰岛素样生长因子-1(IGF-1)时大鼠脑缺血再灌注损伤的影响，探讨IGF-1的作用机制。方法TTC染色测脑梗死体积，光镜检查细胞损伤变化．免疫组化法测Caspase-3阳性表达。结果与缺血再灌注组相比，IGF-1灶性脑缺血再灌注损伤有保护作用，在脑缺血损伤时IGF-1能通过血脑屏障，IGF-1可通过抑制神经细胞调亡发挥作用。     

胰岛素样生长因子1对局灶性脑缺血再灌注损伤保护作用的研究

目的 探讨胰岛素样生长因子1（IGF－1）对局灶性脑缺血再灌注损伤的保护作用。方法 利用TTC染色测定脑梗死体积，同时用酸性品红／硫堇染色进行病理学观察和死亡神经细胞计数。结果 与缺血再灌注组相比，给药组大鼠脑梗死体积显著缩小（P＜0．01）；死亡神经细胞数／总的神经细胞数也明显减小（P＜0．01）。结论 TGF－1缺血再灌注引发的脑损伤起保护作用，IGF－1可能通过抑制凋亡、营养支持等机制而起作用。     

胰岛素样生长因子-1对大鼠脑缺血再灌注损伤的作用机制研究

目的　观察尾静脉注射胰岛素样生长因子 -1(IGF -1)对大鼠脑缺血再灌注损伤的影响 ,探讨IGF -1的作用机制。方法　TTC染色测脑梗死体积 ,光镜检查细胞损伤变化 ,免疫组化法测Caspase -3阳性表达。结果　与缺血再灌注组相比 ,IGF -1用药组脑梗死体积显著缩小 (P <0 0 1) ,光镜下细胞坏死调亡减少 ,Caspase -3阳性细胞数明显下降 (P <0 0 1)。结论　IGF -1对局灶性脑缺血再灌注损伤有保护作用 ,在脑缺血损伤时IGF -1能通过血脑屏障 ,IGF -1可通过抑制神经细胞调亡发挥作用。     

钙与脑缺血/再灌注后神经细胞凋亡

<正> 脑缺血是临床常见脑血管疾病之一,缺血后常导致神经功能缺失。对缺血后神经细胞损伤的机制研究颇多,传统认为脑缺血/再灌注后引起神经细胞完全性坏死,从1990年发现脑缺血可引起神经元凋亡后,许多学者致力于此方面的研究,在动物卒中模型中,神经元也存在胞浆与核固缩以及DNA裂解等凋亡特征。而在神经凋亡中,钙信号异常是神经细胞变性、坏死的“最后通道”。本文拟综述钙与脑缺血/再灌注后神经元凋亡的关系。 [Ca~(2+)i]变化的分子生物学基础 在细胞内,Ca~(2+)参与细胞膜生物电活动和胞内生化过程,对细胞的正常功能起着关键作用。正常神经元内的游离钙浓     

甘露醇对大鼠局灶性脑缺血再灌注损伤时神经细胞凋亡的影响

目的 研究甘露醇对大鼠局灶性脑缺血再灌注损伤时神经细胞凋亡的影响。方法 采用大鼠大脑中动脉阻断（MCAO）模型，给予不同剂量甘露醇进行干预，用TUNEL染色标记大鼠神经细胞凋亡情况，按Swanson方法测量、计算梗死体积，并与未干预组及生理盐水对照组比较。结果 大、小剂量甘露醇均能减轻大鼠脑缺血再灌注后的神经细胞凋亡，并能阻止梗死体积的扩大。大、小剂量的效果之间无明显差异。结论 甘露醇的脑保护作用不完全与脱水降颅压有关，还可通过抑制神经细胞凋亡而发挥重要的脑保护作用。     

重组人粒细胞集落刺激因子对糖尿病脑缺血大鼠神经细胞凋亡及血管内皮生长因子表达的影响

目的探讨重组人粒细胞集落刺激因子(rhG-CSF)对糖尿病脑缺血大鼠神经细胞凋亡及血管内皮生长因子(VEGF)表达的影响。方法制备糖尿病大鼠大脑中动脉栓塞模型;对模型鼠采用rhG-CSF50μg/(kg.d)皮下注射;分别于注射后7d、14d和21d采用神经功能评分(NSS)量表进行评分;对脑组织切片予以TUNEL染色,计数脑缺血周边区神经细胞凋亡数;免疫组化法检测脑组织VEGF表达。结果与对照组比较,rhG-CSF组各时间点NSS明显降低(均P<0.01);脑缺血周边区的TUNEL阳性细胞数明显减少(均P<0.01);VEGF蛋白免疫阳性细胞明显增多(均P<0.01)。结论rhG-CSF通过增加糖尿病脑组织缺血后VEGF蛋白的表达,减轻神经细胞的凋亡而发挥脑保护作用。     

纳洛酮对大鼠全脑缺血—再灌注损伤后神经细胞凋亡的影响

目的:本研究旨在探讨纳洛酮对全脑缺血再灌注损伤后神经细胞的保护作用及机制。方法:选取健康成年雄性Wistar大鼠36只。随机分为假手术组,对照组及治疗组。采用大鼠四条血管阻断方法制备大鼠全脑缺血再灌注模型。治疗组于不同开始时间点累积给药纳洛酮。并于缺血再灌注后48小时处死。采用流式细胞分析技术(Fcm)观察海马区细胞凋亡的变化及Bcl-2、Bax的蛋白表达水平。结果:Fcm标记凋亡细胞的变化:治疗组均与对照组有显著统计学差异(P&lt;0.01)。Bcl-2、bax检查表明治疗组与对照组有显著统计学差异(P&lt;0.01)。结论:纳洛酮可减少脑细胞凋亡的发生,这其中可能与纳洛酮早期上调Bcl-2蛋白的表达或通过减轻Bax对Bcl-2活性的抑制从而降低细胞凋亡的发生有关。     

不同途径应用胰岛素样生长因子1对新生大鼠缺氧缺血性脑损伤的影响

目的 研究不同途径应用胰岛素样生长因子1（IGF-1）对新生大鼠缺氧缺血性脑损伤（HIBD）的影响。方法 40只新生大鼠分为4组：HIBD模型对照组（对照组）、静脉注射组、经鼻腔滴入组和假手术组：给药组于缺氧后分别给予尾静脉注射和经鼻腔滴入IGF-1 2．5μg（溶于生理盐水0．1ml中）;对照组于HIBD后给予等量的生理盐水尾静脉注射;假手术组仅分离颈总动脉,不结扎不缺氧。24h后处死取脑组织,免疫组化法观察脑组织caspase-3的表达,组织学方法观察脑组织病理改变情况。结果 与对照组相比,给药各组caspase-3表达减少（均P〈0．01）,神经细胞总数增加（均P〈0．01）,变性／坏死神经细胞数减少（均P〈0．01）,结论 静脉注射和鼻腔滴入IGF-1均可能通过降低HIBD脑组织中caspase-3表达,从而对HIBD脑组织损伤产生保护作用。     

内质网应激与脑缺血再灌注后的神经细胞凋亡

脑血管疾病是神经系统常见病和多发病，其中缺血性脑血管病占较大比例。脑缺血后有相当部分血管能自然再通或经溶栓治疗后恢复再通，但随之而来的是出现再灌注损伤，导致缺血及周边区神经细胞坏死和凋亡。脑缺血再灌注损伤中的神经细胞凋亡机制目前仍未完全阐明。内质网应激（endoplasmic retieulum stress，ERS）是细胞的一种自我保护机制，以恢复内质网稳态，维持生存，但是过强或持续时间过长的ERS可以引起细胞凋亡。ERS反应性凋亡途径是不同于经典凋亡途径（死亡受体途径和线粒体途径）的一种新的细胞凋亡途径，ERS与脑缺血再灌注后神经细胞凋亡关系的研究是近年来脑血管病研究的热点，本文就相关内容作一综述。     

褪黑素对SD大鼠脑缺血再灌注损伤后c-fos表达的影响

目的探讨褪黑素在大鼠脑缺血再灌注损伤中的神经保护作用及可能机制。方法选取45只雄性SD大鼠,分为假手术组(5只)、脑缺血再灌注组(20只)、褪黑素干预组(20只);脑缺血再灌注组和褪黑素干预组根据时间点第6小时、第1天、第3天、第7天分为4个组,每组5只。采用Longa线栓法建立大鼠左侧大脑中动脉栓塞(MCAO)模型,采用HE染色检测脑组织的病理改变,TUNEL染色检测神经细胞的凋亡,免疫组织化学(免疫组化)法及蛋白质印迹法(Western Blotting)观察大鼠脑组织内c-fos表达情况。结果在脑缺血再灌注组的各时间点的HE染色显示,胶质细胞呈现程度不一的增生,神经元出现坏死;褪黑素干预能减轻脑缺血再灌注后胶质细胞增生及神经元的坏死。在TUNEL染色凋亡检测中,脑缺血再灌注组各时间点的神经细胞凋亡升高;褪黑素干预组各时间点的细胞凋亡数低于脑缺血再灌注组(P <0.05)。在免疫组化及蛋白质印迹检测中,脑缺血再灌注组c-fos表达增加,在第1天时达到高峰,之后表达逐步降低;在褪黑素干预组,c-fos表达趋势与缺血再灌注组一致,但表达水平比缺血再灌注组相应时间点低,差异有统计学意义(P <0.05)。结论褪黑素能够减轻脑缺血再灌注后神经元的损伤,降低c-fos的表达,表明褪黑素可能通过调控c-fos的表达在脑缺血再灌注中发挥神经保护作用。     

Changes in neuronal apoptosis and apoptosis modulatory factors in cerebral ischemia/reperfusion

BACKGROUND: The high concentration of glutamate release is the main cause for neuronal cell death. The relationship between glutamate level and apoptosis during ischemia/reperfusion injury is still unclear. OBJECTIVE: To observe the neuronal apoptosis at 24 and 72 hours following cerebral ischemia/reperfusion in rats, and analyze the possible influencing factors. DESIGN: A randomized controlled animal experiment. SETTING: School of Medicine, Southern Yangtze University. MATERIALS: Totally 30 male adult Sprague Dawley (SD) rats of clean grade, weighing 240–290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. The rats were randomly divided into sham-operated group (n=10) and model group (n=20). Each group was observed at 24 and 72 hours after ischemia/reperfusion, 5 rats at each time point in the sham-operated group, whereas 12 at 24 hours and 8 at 72 hours in the model group. Kits for determining apoptosis and Bcl-2 were bought from Wuhan Boster Biological Technology, Co., Ltd.; Kit for calcineurin from Nanjing Jiancheng Bioengineering Institute. METHODS: The experiment was carried out in the Functional Scientific Research Room of Southern Yangtze University from June to October in 2006. ① Right middle cerebral artery was occluded by inserting a thread through internal carotid artery (ICA). The surgical process for the sham-operated rats was the same as that in the model group except a nylon suture inserted the ICA. According to Longa five-degree standard, the neurological deficit evaluation of rats was evaluated after surgery, and grades 1–3 were taken as successful model establishment. The blood was recirculated by withdrawing the nylon filament under anesthesia at 2 hours after ischemia in successful rat models. ②After reperfusion, the brain tissue was quickly removed at 24 or 72 hours and the slices were obtained from optic chiasma to funnel manubrium. The changes of the number of apoptotic cells were observed using the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling method. The expressions of Bcl-2 protein were determined with immunohistochemical staining. The activity of calcineurin was determined by the inorganic phosphorus method. The content of excitatory amino acid was detected by high performance liquid chromatography. MAIN OUTCOME MEASURES: ① Glutanate content in brain tissue; ② Conditions of apoptosis; ③ Calcineurin activity in brain tissue; ④ Bcl-2 expression in brain tissue. RESULTS: Totally 30 SD rats were used, 5 died and the other 25 were involved in the analysis of results. ① Changes of apoptosis: There were 0–3 apoptotic cells in the sham-operated group. In the model group, the numbers of apoptotic cells were obviously increased at 24 and 72 hours of reperfusion (P < 0.01), and it was markedly reduced at 72 hours as compared with 24 hours (P < 0.01). ② Changes of glutanate content: The glutamate contents at 24 and 72 hours of reperfusion in the model group were obviously higher than those in the sham-operated group (P < 0.01); In the model group, it was obviously increased at 24 hours as compared with 72 hours (P < 0.01). ③ Changes of Bcl-2 protein: In the model group, the Bcl-2 protein expression had no obvious changes at 24 hours of reperfusion, and it was obviously enhanced at 72 hours, which was obviously different from that in the sham-operated group and that at 24 hours (P < 0.01). ④ Changes of calcinerin activity: In the model group, the activity of calcineurin in brain tissue had no obvious changes at 24 hours of reperfusion; The activity of calcineurin at 72 hours was obviously higher than that in the sham-operated group and that at 24 hours (P < 0.01). CONCLUSION: The brain cyto-apoptosis action at different time points following reperfusion incompletely depends on the glutamate levels, while it depends on the interaction of some apoptosis related factors, such as amino acid, calcineurin, and Bcl-2, etc.     

一氧化氮在脑缺血再灌流神经损伤中作用的实验研究

采用改良的Ｇｒｉｅｓｓ法，测定了脑缺血再灌流大鼠血清和脑组织中一氧化氮（ＮＯ）代谢产物ＮＯｘ（ＮＯ２＋ＮＯ３）的含量。结果表明，在脑缺血再灌流过程中实验大鼠血清和脑组织中ＮＯｘ含量的变化表现出独特的双峰现象，其第二高峰的出现时间与迟发性神经元损伤的发生相吻合。这提示，ＮＯ在脑缺血再灌流神经损伤中可能具有重要作用。     

小檗碱对小鼠全脑缺血后神经元凋亡的影响

目的观察小檗碱能否对小鼠全脑缺血后细胞凋亡产生抑制作用.方法利用改良的Pulsinelli-Brierley4血管闭塞法制成小鼠全脑缺血再灌注动物模型.TUNEL法原位检测特征性DNA片段.琼脂糖凝胶电泳技术检测DNA梯度带.结果小檗碱组与再灌流各时间段缺血组相比,海马CA1区TUNEL阳性细胞数明显减少(P<0.01).缺血组再灌注24h、48h可见典型的DNA梯度带,分别在180、360、540bp等处.小檗碱组未见特征性DNA梯度带.结论小檗碱可以减少小鼠全脑缺血后海马CA1区细胞凋亡的发生.     

神经节苷脂对大鼠脑缺血再灌注损伤的脑保护作用

目的探讨神经节苷脂对大鼠脑缺血再灌注损伤的脑保护作用。方法采用线栓法制作缺血再灌注大鼠模型,分别用神经节苷脂(治疗组)和生理盐水(对照组)腹腔注射。观察两组大鼠缺血90min、缺血90min再灌注24h的脑梗死面积、神经功能缺损程度、细胞凋亡数、细胞凋亡率。结果治疗组大鼠于相同时间点脑梗死面积较对照组明显减小,仅表现轻度的神经功能缺损,且神经细胞的凋亡数较对照组显著减少(均P<0.01)。结论神经节苷脂能明显减小大鼠实验性脑缺血的脑梗死面积,减轻脑缺血再灌注后神经功能缺损程度,显著减轻缺血区神经元损害,具有显著的脑保护作用。     

Inhibitory effect of acupuncture on neuronal apoptosis in rats after cerebral ischemia

BACKGROUND: Delayed neuronal death after total cerebral ischemia may accompany with apoptosis, but acupuncture may play a certain role in protecting nerve through inhibiting ischemic neuronal apoptosis. OBJECTIVE: To observe the effect of acupuncture on neuronal apoptosis in rats after cerebral ischemia and analyze its cerebral protective mechanism. DESIGN: Contrast observation among groups. SETTING: Heilongjiang University of Traditional Chinese Medicine. MATERIALS: A total of 30 male healthy Wistar rats of general grade and weighing (250±20) g were randomly divided into three groups, including sham operation group, cerebral ischemia group and acupuncture group with 10 rats in each group. Apoptosis in situ kit was provided by Baolingman Company, Germany. METHODS: The experiment was carried out in the Laboratory Center, Heilongjiang University of Traditional Chinese Medicine from May to November 2004. ① Rats in the cerebral ischemia group and the acupuncture group were used to establish total cerebral ischemic models with four vessels occlusion; in addition, models in the sham operation group were established with the same method as mentioned above. However, four vessels of rats in the sham operation were exposured and cerebral ischemia did not occur. Rats in the acupuncture group were given acupuncture treatment after operation. Needle of 40 mm in length was used to acupuncture bilateral Zusanli (St 36) and Quchi (LI 11) with the depth of 3 mm, and then bilateral acupoints were connected with KWD-808II omnipotenc impulse electro-therapeutic apparatus (frequency: 1 Hz; thin waves; voltage: 2 V) once a day for totally 30 minutes. Meanwhile, needle of 25 mm in length was used to acupuncture Baihui (Du 20) with the depth of 3 mm, and then the needle was twirled once every 5 minutes for 30 minutes in total. The course was 7 days. ② Neuronal injuries in hippocampal CA1 area after cerebral ischemia were observed with Nissl body staining method at 7 days after treatment; neuronal apoptosis was observed with TUNEL staining; manifestations of neuronal apoptosis in cerebral cortex and hippocampal CA1 area were observed with electron microscope. MAIN OUTCOME MEASURES: Neuronal injuries in hippocampal CA1 area after cerebral ischemia; neuronal apoptosis in cerebral cortex and hippocampal CA1 area after cerebral ischemia; morphological changes under electron microscope. RESULTS: Among 30 Wistar rats, 24 rats were involved in the final analysis. ① Expression of positive neurons in cerebral cortex and hippocampal CA1 area with Nissl body staining: Neuronal defect was obvious in cerebral cortex and hippocampal CA1 area in the cerebral ischemia group as compared with that in the sham operation group (P < 0.05), and neuronal defect was decreased in hippocampal CA1 area in the cerebral ischemia group as compared with that in the acupuncture group (P < 0.05). ② Expression of positive neurons in cerebral cortex and hippocampal CA1 area with TUNEL staining: Positive neurons with TUNEL staining were not observed in the sham operation group, but positive neurons were increased in the cerebral ischemia group as compared with those in the acupuncture group (P <0.05). ③ Observational results of electron microscope: Neuronal apoptosis was not found in the sham operation group; neuronal apoptosis was rarely found in the acupuncture group; neuronal apoptosis was typical in the cerebral ischemia group. CONCLUSION: Delayed neuronal death after total cerebral ischemia may accompany with apoptosis, but acupuncture may play a certain role in protecting nerve through inhibiting ischemic neuronal apoptosis.     

Expression profiles of microRNAs after focal cerebral ischemia/reperfusion injury in rats

Rat models of focal cerebral ischemia/reperfusion injury were established by occlusion of the middle cerebral artery.Microarray analysis showed that 24 hours after cerebral ischemia,there were nine up-regulated and 27 down-regulated microRNA genes in cortical tissue.Bioinformatic analysis showed that bcl-2 was the target gene of microRNA-384-5p and microRNA-494,and caspase-3 was the target gene of microRNA-129,microRNA-320 and microRNA-326.Real-time PCR and western blot analyses showed that 24 hours after cerebral ischemia,bcl-2 mRNA and protein levels in brain tissue were significantly decreased,while caspase-3 mRNA and protein levels were significantly increased.This suggests that following cerebral ischemia,differentially expressed microRNA-384-5p,microRNA-494,microRNA-320,microRNA-129 and microRNA-326 can regulate bcl-2 and caspase-3 expression in brain tissue.     

小檗碱对小鼠全脑缺血后神经元凋亡相关基因的影响

目的 探讨小檗碱对小鼠全脑缺血后神经元凋亡相关基因的影响,以了解小檗碱保护脑缺血的机制,为其开发利用提供理论依据。方法 利用改良的Pulsinelli-Brierley4血管闭塞法制成小鼠全脑缺血再灌注动物模型。小檗碱用量为1mg/kg,于术前30min,术后每日1次,腹腔注射。免疫组织化学技术检测凋亡相关基因Bcl-2,Bax蛋白的表达。结果 正常组海马区未见Bcl-2或Bax蛋白表达;缺血组再灌注6h海马CA3区可见Bcl-2阳性细胞,24h达到高峰,48h开始下降;小檗碱治疗组再灌注24h、48h及168hBcl-2阳性细胞明显减少（P＜0．01）。缺血组再灌注6h海马CA1区可见Bax阳性细胞;48h达高峰;168h明显下降;小檗碱组再灌注24h,48h及168hBax阳性细胞数明显减少（P＜0．01）。结论 小檗碱可以增加小鼠全脑缺血后海马CA3区bcl-2基因的表达,降低CA1区Bax基因的表达,从而减少凋亡的发生,可能为其保护脑缺血的机制之一。     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.