肢体缺血预处理减轻大鼠海马缺血/再灌注损伤

目的:探讨肢体缺血预处理(LIP)对大鼠全脑缺血/再灌注损伤的影响.方法: 36只大鼠椎动脉凝闭后随机分为假手术(Control)组、脑缺血组、肢体缺血组、LIP 0 d组(LIP后即刻行脑缺血)、LIP 1 d组(LIP后1 d行脑缺血)和LIP 2 d组(LIP后2 d行脑缺血).重复夹闭大鼠双侧股动脉3次(每次10 min,间隔10 min)作为LIP,夹闭颈总动脉进行全脑缺血8 min后再灌注.硫堇染色观察海马CA1区组织学分级及锥体神经元密度以判断海马损伤程度.结果:脑缺血组海马CA1区锥体神经元损伤严重,与Control组比较,组织学分级明显升高,神经元密度明显降低(P<0.01).LIP 0 d组海马CA1区神经元损伤较脑缺血组明显减轻,组织学分级明显降低,神经元密度明显升高(P<0.01).而LIP 1 d组和LIP 2 d组大鼠海马CA1区锥体细胞缺失较多,仍有明显的组织损伤.结论:LIP可减轻随后立即发生的脑缺血/再灌注损伤,但对间隔1 d后的脑缺血/再灌注损伤无显著对抗作用.     

大蒜素对全脑缺血/再灌注诱导的海马神经元凋亡的影响

目的:观察大蒜素对全脑缺血/再灌注诱导的海马神经元凋亡的影响。方法:采用大鼠全脑缺血/再灌注模型;应用DNA琼脂糖凝胶电泳、透射电镜和流式细胞仪检测海马神经元凋亡情况。结果:缺血/再灌注大鼠海马DNA电泳呈现细胞凋亡特有的"梯状条带",大蒜素预处理组未出现"梯状条带";透射电镜观察到缺血/再灌注海马部分神经元超微结构呈现明显的凋亡特征,大蒜素预处理可改善神经元超微结构;缺血/再灌注海马神经元凋亡率较假手术组明显增加,大蒜素预处理可明显降低缺血/再灌注大鼠海马神经元凋亡率。结论:大蒜素可抑制全脑缺血/再灌注诱导的海马神经元凋亡。     

大蒜素对全脑缺血侑灌注诱导的海马神经元凋亡的影响

的：观察大蒜素对全脑缺血／再灌注诱导的海马神经元凋亡的影响：方法：采用大鼠全脑缺血／再灌注模型;应用DNA琼脂糖凝胶电泳、透射电镜和流式细胞仪检测海马神经元凋亡情况结果：缺血／再灌注大鼠海马DNA电泳呈现细胞凋亡特有的“梯状条带”,大蒜素预处理组未出现“梯状条带”;透射电镜观察到缺血／再灌注海马部分神经元超微结构呈现明显的凋亡特征,大蒜素预处理可改善神经元超微结构;缺血／再灌注海马神经元凋亡率较假手术组明显增加,大蒜素预处理可明显降低缺血／再灌注大鼠海马神经元凋亡率,结论：大蒜素可抑制全脑缺血／再灌注诱导的海马神经元凋亡、     

神经途径在肢体缺血预处理抗脑缺血/再灌注损伤中的作用

目的：探讨神经途径在肢体缺血预处理（limbi schemic preconditioning,LIP）抗脑缺血／再灌注损伤中的作用。方法：脑缺血采用四血管闭塞模型,重复短暂夹闭放松大鼠双侧股动脉3次作为LIP。将凝闭椎动脉的大鼠随机分为sham组、脑缺血组、股神经切断＋脑缺血组、LIP＋脑缺血组、股神经切断＋LIP＋脑缺血组。于Sham手术和脑缺血后7d处死大鼠,硫堇染色观察海马CA1区锥体神经元迟发性死亡的变化。于Sham手术和脑缺血后6h心脏灌注固定大鼠,免疫组化法测定海马CAI区c-Fos表达的变化。结果：硫堇染色结果显示,与sham组比较。脑缺血组和股神经切断＋脑缺血组大鼠海马CAI区均有明显组织损伤。LIP＋脑缺血组CAI区无明显细胞缺失,神经元密度明显高于脑缺血组（P〈0．01）。而股神经切断＋LIP＋脑缺血组大鼠海马CA1区明显损伤,锥体细胞缺失较多,与LIP＋脑缺血组组比较,神经元密度显著降低（P〈O．01）,提示LIP前切断双侧股神经取消了LIP抗脑缺血／再灌注损伤作用。c—Fos免疫组化染色结果显示,Sham组海马CAI区未见明显的c-Fos蛋白表达。脑缺血组海马CAI区偶见c—Fm的阳性表达。LIP＋脑缺血组c—Fos表达增强,数量增加,与Sham组和脑缺血组比较。c-Fos阳性细胞数和光密度均明显升高（P〈0．01）。而股神经切断＋LIP＋脑缺血组c-Fos表达明显减少,仅见少量弱阳性e-Fos表达。结论：LIP可通过神经途径发挥抗脑缺血／再灌注损伤作用,而LIP诱导c—Fos表达增加可能是LIP诱导脑缺血耐受神经途径的一个环节。     

姜黄素对自发性高血压大鼠海马缺血/再灌注损伤神经元凋亡核通路的影响

目的:探讨自发性高血压大鼠(SHR)脑缺血/再灌注损伤海马神经元凋亡c-Jun氨基末端激酶(JNK)核通路的变化特点,以及姜黄素对其保护作用可能机制。方法:雄性Wistar-Kyoto大鼠(WKY)和SHR,随机分为5组:WKY假手术组(W-Sham组)、缺血/再灌注组(W-I/R组)和SHR假手术组(S-Sham组)、缺血/再灌注组(S-I/R组)、姜黄素100mg/kg预处理组(S-Cur组),上述5个实验组按再灌注时间又分为再灌注2h、6h、1d、3d、7d5个亚组(n=6)。采用四动脉结扎法制备脑缺血/再灌注模型,以TUNEL法检测海马CA1区的细胞凋亡,免疫组化法分析海马CA1区c-jun、c-fos的动态变化。结果:S-Sham组大鼠海马CA1区TUNEL细胞数量和c-jun、c-fos表达高于W-Sham组(P0.05),S-I/R组TUNEL细胞数量和c-jun、c-fos表达高于S-Sham组及W-I/R组(P0.05);S-Cur组TUNEL细胞数量和c-jun、c-fos表达较S-I/R组明显降低(P0.05)。结论:缺血/再灌注更易导致SHR海马神经元凋亡。姜黄素可抑制SHR脑缺血/再灌注损伤海马神经元凋亡,其作用机制可能与抑制c-jun、c-fos蛋白的表达有关。     

20-羟基蜕皮甾酮对大鼠全脑缺血再灌注后海马神经元损伤和炎症反应的影响

目的:观察20-羟基蜕皮甾酮对全脑缺血再灌注后SD大鼠海马神经元和认知功能的保护作用,并探讨其相关机制。方法:采用四血管闭塞法建立SD大鼠全脑缺血再灌注模型,脑电图和脑组织Nissl染色评估模型的可靠性。将实验动物分为假手术组,缺血再灌注组和缺血再灌注+20-羟基蜕皮甾酮组。TUNEL染色观察海马神经元凋亡,Morris水迷宫实验评价大鼠的认知功能,酶联免疫法测定缺血再灌注后3-24小时大鼠血清中白细胞介素-1β(IL-1β)和肿瘤坏死因子α(TNF-α)的浓度。结果:全脑缺血再灌注后大鼠海马神经元凋亡率从4.50±1.90%上升至72.90±8.40%(p0.01),给予20和40 mg/kg 20-羟基蜕皮甾酮干预,大鼠海马神经元凋亡率分别下降至51.40±8.60%(p0.05)和42.70±6.80%(p0.01)。与假手术组相比,全脑缺血再灌注后大鼠在Morris水迷宫定位航行试验中逃避潜伏期明显延长(p0.01),在空间探索试验中目标象限停留时间和穿越目标象限次数明显减少(p0.01),而20-羟基蜕皮甾酮显著抑制上述变化,改善大鼠的认知功能。缺血再灌注后3-24小时,大鼠血清中IL-1β和TNFα浓度较假手术组显著升高,20-羟基蜕皮甾酮能抑制上述各时间点大鼠血清中IL-1β和TNFα浓度的升高。结论:20-羟基蜕皮甾酮对全脑缺血再灌注后大鼠海马神经元和认知功能有显著保护作用,抑制缺血再灌注后的炎症反应是其保护机制之一。     

镁预处理对兔全脑缺血神经保护作用的实验研究

目的探讨硫酸镁预处理对兔全脑缺血神经保护作用及其机制.方法 45只兔随机分为3组:对照组(n=15)、缺血组(n=15)和镁预处理组(n=15).阻断血管,诱导全脑缺血,缺血时间为 6 min.测定缺血再灌注30 min 兔海马谷氨酸、天冬氨酸、γ-氨基丁酸和甘氨酸含量.检测缺血再灌注3 d 海马CA1区神经元密度和凋亡神经元密度.结果 (1)镁预处理组海马天冬氨酸和甘氨酸显著低于缺血组(P<0.01),而γ-氨基丁酸含量显著高于缺血组(P<0.05);(2)镁预处理组正常神经元密度显著高于缺血组 (P<0.01),缺血神经元密度显著低于缺血组(P<0.01);(3)镁预处理组凋亡神经元密度显著低于缺血组(P<0.01).结论 (1)硫酸镁预处理对兔全脑缺血有神经保护作用;(2)该保护作用的机制可能有:1)抑制兔全脑缺血再灌注30 min 海马天冬氨酸和甘氨酸的过度释放以及抑制γ-氨基丁酸的耗竭;2)抑制兔全脑缺血再灌注3 d 海马CA1区神经元凋亡.     

全脑缺血/再灌注大鼠海马PPARγ mRNA表达变化

目的 观察大鼠全脑缺血/再灌注损伤后海马PPARγ mRNA表达的动态变化.方法 采用夹闭双侧颈总动脉,颈总静脉抽血后回输建立大鼠全脑缺血/再灌注损伤模型.Morris水迷宫检测大鼠空间定向能力变化,HE染色观察海马病理组织学改变及RT-PCR法检测缺血再灌注后不同时间点PPARγ mRNA的表达变化.结果 全脑缺血/再灌注损伤导致大鼠空间学习及记忆能力明显下降,海马神经元出现明显的核固缩和细胞丢失.PPARγ mRNA的表达先升高后降低,以缺血/再灌注后48 h表达水平最高,30 d后接近正常水平.结论 全脑缺血/再灌注损伤大鼠海马组织中PPARγ mRNA的表达,在再灌注30 d内明显增加,表达高峰在48 h.     

p38 MAPK反义寡聚脱氧核苷酸阻断肢体缺血预处理诱导的脑缺血耐受

目的:观察p38MAPK反义寡聚脱氧核苷酸(As-ODN)对肢体缺血预处理(LIP)诱导的脑缺血耐受的影响。方法:48只永久凝闭双侧椎动脉的Wistar大鼠分为8组(n=6):sham组、LIP组、脑缺血损伤组、LIP+脑缺血损伤组、双蒸水+LIP+脑缺血损伤组、p38MAPKAs-ODN组和p38MAPKAs-ODN+LIP+脑缺血损伤组,p38MAPKAs-ODN的剂量又分为5nmol/5μl和10nmol/5μl。所有动物均在sham手术后或末次全脑缺血/再灌注后7天断头取脑,硫堇染色观察海马CA1区锥体神经元迟发性死亡情况。结果:sham组和LIP组均未见延迟性神经元死亡(DND)。与sham、LIP组相比,脑缺血损伤组出现了明显的DND,表现为组织学分级(HG)升高和锥体神经元密度(ND)下降(P0.05)。LIP可显著抑制脑缺血损伤引起的DND。与LIP+脑缺血损伤组相比,p38MAPKAs-ODN+LIP+脑缺血损伤组出现了显著的DND,表现为HG升高、ND降低(P0.05),且此种变化与p38MAPKAs-ODN的注射剂量呈明显正相关。结论:p38MAPKAs-ODN可阻断LIP诱导的脑缺血耐受,进一步证实了p38MAPK表达上调参与了LIP诱导的脑缺血耐受。     

大鼠局灶性脑缺血后不同时间点磷酸化Rb蛋白与凋亡神经元的共定位研究

目的探讨大鼠局灶性脑缺血后磷酸化Rb蛋白(p-Rb,ser 795)的表达定位与神经元凋亡的时空关系。方法制备大鼠大脑中动脉梗塞(MCAO)模型,分为假手术对照组、缺血1h再灌注12h,1d,3d,7d组。利用TUNEL法检测缺血周边区细胞凋亡情况;TUNEL与p-Rb荧光双标观察神经元凋亡与p-Rb表达、定位的关系。结果缺血半暗带内大部分TUNEL阳性细胞为神经元;大鼠MCAO再灌注12h和1d,TUNEL与p-Rb分别以重叠和镶嵌的方式共定位;再灌注3d,7d发生p-Rb核浆转移的神经元与TUNEL染色细胞仍然分别维持在高水平,但是两者却没有明显的共定位关系。结论 p-Rb可能参与短暂局灶脑缺血后神经元早期凋亡过程,间接或者不参与神经元晚期凋亡过程。     

凝闭双侧椎动脉预处理对大鼠全脑缺血损伤的防护作用

目的：观察凝闭双侧椎动脉与夹闭双侧颈总动脉之间的不同时间间隔对Pulsinelli四血管闭塞法全脑缺血模型的影响、以及在凝闭单侧椎动脉的基础上夹闭双侧颈总动脉后的脑缺血的特点。方法：84只Wistar大鼠．随机分为以下4组：对照组、双侧椎动脉凝闭组、全脑缺血组、单侧椎动脉凝闭＋双侧颈总动脉夹闭组。全脑缺血组中,根据凝闭双侧椎动脉与夹闭双侧颈总动脉之间的时间间隔不同,又分为24h间隔、48h间隔和72h间隔3个亚组。观察大鼠脑缺血过程中的反应包括瞳孔散大、对光反射等情况,脑缺血后恢复翻正反射所需要的时间、以及动物的一般状况,并应用硫堇染色法观察海马CA1区锥体神经元迟发性死亡的情况：结果：全脑缺血72h间隔亚组的大鼠,脑缺血过程中的反应、脑缺血后的一般状况和锥体神经元迟发性死亡程度均明显重于全脑缺血24h间隔亚组及48h间隔亚组,但24h间隔亚组与48h间隔亚组之间无显著差异一单侧椎动脉凝闭＋双侧颈总动脉夹闭组大鼠的凝闭侧瞳孔散大、对光反射消失、海马CA1区神经元大量死亡;而未凝闭侧未见上述相关变化。结论：凝闭双侧椎动脉本身也具有脑缺血预处理样作用,对其后48h内夹闭双侧颈总动脉所致的严重脑缺血具有一定程度的保护作用;大鼠椎动脉对脑干及海马的血液供应均存在明显的同侧优势效应,     

The Role of Nitric Oxide in the Neuroprotection of Limb Ischemic Preconditioning in Rats

Brief limb ischemia was reported to protect neurons against injury induced by subsequent cerebral ischemia-reperfusion, and this phenomenon is known as limb ischemic preconditioning (LIP). To explore the role of nitric oxide (NO) in neuroprotection of LIP in rats, we observed changes in the content of nitric oxide (NO) and activity of NO synthase (NOS) in the serum and CA1 hippocampus of rats after transient limb ischemic preconditioning (LIP), and the influence of N^G-nitro-l-arginine methylester (l-NAME), a NOS inhibitor, on the neuroprotection of LIP against cerebral ischemia-reperfusion injury. Results showed that NO content and NOS activity in serum increased significantly after LIP compared with the sham group. The increase showed a double peak pattern, in which the first one appeared at time 0 (immediate time point) and the second one appeared at 48 h after the LIP (P < 0.01). The NO content and NOS activity in the CA1 hippocampus in LIP group showed similar change pattern with the changes in the serum, except for the first peak of up-regulation of NO content and NOS activity appeared at 6 h after LIP. Pretreatment with l-NAME before LIP blocked the neuroprotection of LIP against subsequent cerebral ischemic insult. The blocking effect of l-NAME was abolished with pretreatment of l-Arg. These findings indicated that NO may be associated with the tolerance of pyramidal cells in the CA1 hippocampus to ischemia induced by LIP in rats.     

Recombinant human superoxide dismutase can attenuate ischemic neuronal damage in gerbils.

The effects of recombinant human superoxide dismutase (r-hSOD) on ischemic neuronal injury were examined. Cerebral ischemia was produced in Mongolian gerbils by occluding bilateral common carotid arteries for 5 min. Preischemic treatment with r-hSOD clearly reduced hippocampal neuronal damages while postischemic treatment did not. This result suggests that oxygen free radicals play an important role in selective vulnerability to ischemia and r-hSOD has a potential clinical usefulness against cerebral ischemia.     

胶质细胞谷氨酸转运体-1反义寡核苷酸对脑缺血预处理神经保护效应的抑制作用

本研究应用胶质细胞谷氨酸转运体-1(glial glutamate transporter-1,GLT-1)的反义寡核苷酸(antisense oligo-deoxynucleotides,AS-ODNs)抑制Wistar大鼠GLT-1蛋白的表达,观察其对脑缺血预处理(cerebral ischemic preconditioning.CIP)增强脑缺血耐受作用的影响,探讨GLT-1在CIP诱导的脑缺血耐受中的作用.将凝闭双侧椎动脉的Wistar大鼠随机分为7组:(1)Sham组:只暴露双侧颈总动脉,不阻断血流;(2)CIP组:夹闭双侧颈总动脉3 min;(3)脑缺血打击组:夹闭双侧颈总动脉8 min;(4)CIP 脑缺血打击组:夹闭双侧颈总动脉3 min作为CIP,再灌注2 d后,夹闭双侧颈总动脉8min;(5)双蒸水组:于分离暴露双侧颈总动脉(但不夹闭)前12 h、后12 h及后36 h右侧脑室注射双蒸水,每次5 μL,其它同sham组;(6)AS-ODNs组:于分离暴露双侧颈总动脉(但不夹闭)前12 h、后12 h及后36 h右侧脑室注射GLT-1 AS-ODNs溶液,每次5 μL,其它同sham组,再根据AS-ODNs的剂量进一步分为9 nmol和18 nmol 2个亚组;(7)AS-ODNs CIP 脑缺血打击组:于CIP前12 h、后12 h及后36 h右侧脑室注射GLT-1 AS-ODNs溶液,每次5 μL,其它同CIP 脑缺血打击组,根据AS-ODNs的剂量进一步分为9 nmol和18 nmol 2个亚组.Western blot分析法观察GLT-1蛋白的表达,硫堇染色观察海马CA1区锥体神经元迟发性死亡(delayed neuronal death,DND)情况.Western blot分析显示,侧脑室注射GLT-1 AS-ODNs可剂量依赖性地抑制大鼠海马CA1区GLT-1蛋白表达.硫堇染色显示,sham组和CIP组海马CA1区未见明显的DND;脑缺血打击组海马CA1区有明显的DND:预先给予CIP可显著对抗脑缺血打击引起的DND,表明CIP可以诱导海马CA1区神经元产生缺血性耐受,对抗脑缺血打击引起的DND;而在GLT-1 AS-ODNs CIP 脑缺血打击组,侧脑室注射GLT-1 AS-ODNs后,大鼠海马CA1区出现了明显的DND,表明GLT-1 AS-ODNs通过抑制大鼠GLT-1蛋白表达从而减弱CIP对抗脑缺血打击的神经保护作用.以上结果进一步证实了GLT-1参与CIP诱导的脑缺血耐受.     

Protective Effect of Oren-gedoku-to Against Induction of Neuronal Death by Transient Cerebral Ischemia in the C57BL/6 Mouse

We examined the neuroprotective effects of oren-gedoku-to (TJ15), a herbal medicine, after transient forebrain ischemia. Transient forebrain ischemia was induced by occlusion of both common carotid arteries for 15 min in C57BL/6 mice treated with TJ15. In the control ischemic group without TJ15 treatment, histologic examination of brain tissue collected seven days after reperfusion showed death of pyramidal cells in CA2-3 area of the hippocampus, unilaterally or bilaterally. In mice treated with oral TJ15 (845 mg/kg/day) for five weeks, the frequency of ischemic neuronal death was significantly lower. Immunohistochemistry for Cu/Zn-superoxide dismutase (Cu/Zn-SOD) showed strongly reactive astrocytes in the hippocampus of ischemic mice treated with TJ15. Damage to nerve cells by free radicals plays an important role in the induction of neuronal death by ischemia-reperfusion injury. Our results suggest that TJ15 protects against ischemic neuronal death by increasing the expression of Cu/Zn-SOD and suggest that oren-gedoku-to reduces the exposure of hippocampal neurons to oxidative stress.     

丰富环境对脑缺血再灌注小鼠神经细胞凋亡和XIAP基因表达的影响

该研究主要探讨丰富环境干预对脑缺血再灌注小鼠神经细胞凋亡的影响。实验采用健康雄性ICR 小鼠,随机分为丰富环境缺血组(IE)、标准环境缺血组(IS),同时分别设丰富环境假手术组(SE)、标准环境假手术组(SS)。通过双侧颈动脉重复结扎建立小鼠全脑缺血再灌注模型,分别在缺血后在丰富环境和标准环境饲养3 d或7 d 后,进行开场行为和水迷宫空间记忆行为检测;同时进行神经细胞损伤的组织学观测,并采用琼脂糖凝胶电泳技术分析DNA 片段化,用RT-PCR 检测X 染色体连锁的凋亡抑制蛋白（X-linked inhibitor of apoptosis protein,XIAP） mRNA的表达。结果表明,丰富环境干预能有效改善脑缺血导致的自发活动、探究行为减少和空间学习记忆能力减退,并对正常小鼠也有促进作用。缺血再灌注4 d的海马神经细胞损伤较严重,神经元密度显著减少,脑组织DNA 片段化明显增强,丰富环境作用使神经细胞损伤和DNA 片段化程度均有所减轻。同时丰富环境作用可抑制反复脑缺血再灌注导致的XIAP mRNA 表达下调。可见,丰富环境干预可改善脑缺血小鼠的自发活动、探究行为和空间学习记忆能力,该作用可能与其抑制神经细胞XIAP基因表达下调、减弱脑缺血再灌注诱导的神经细胞凋亡有关。     

The Role of Neuroglobin in the Neuroprotection of Limb Ischemic Preconditioning in Rats

Recent evidence suggests that limb ischemic preconditioning (LIP) protects neurons against cerebral ischemia-reperfusion injury. However, the mechanisms of LIP are not well understood. Neuroglobin (Ngb) is a recently discovered globin that affords protection against hypoxic/ischemic brain injury. This study was performed to investigate the role of Ngb in the neuroprotection of LIP against brain ischemia and the involvements of mitochondria in the process. The rat global brain ischemic model was used, and the CA1 hippocampus was selected as the observational target. Ngb expression was investigated by RT-PCR and Western blot. Neuropathological evaluation was performed by thionin staining. Mitochondrial membrane potential (Δψm), Na⁺-K⁺-ATPase activity, and ultrastructure were examined by flow cytometry, spectrophotometry, and transmission electron microscopy, respectively. We also used Ngb antisense oligodeoxynucleotides (AS-ODNs) and Ngb inducer hemin to inhibit or mimic the effect of LIP. We found that LIP significantly up-regulated Ngb expression and protected neurons against ischemia. Furthermore, LIP effectively improved deterioration in the Δψm, mitochondrial Na⁺-K⁺-ATPase activity, and ultrastructure induced by cerebral ischemia. These effects of LIP were inhibited partly by Ngb AS-ODNs and mimicked by hemin. It could be concluded that up-regulation of Ngb expression played an important role in the neuroprotection induced by LIP, and the Ngb-mediated neuroprotection of LIP was, at least partly, associated with mitochondria.     

Ischemia-Induced Mitochondrial Apoptosis is Significantly Attenuated by Ischemic Preconditioning

Ischemic preconditioning (IPC) represents an important adaptation of CNS to sub-lethal ischemia, which results in increased tolerance of CNS to the lethal ischemia. Ischemia-induced mitochondrial apoptosis is considered to be an important event leading to neuronal cell death after cerebral blood flow arrest. In presented study, we have determined the effect of IPC on ischemia/reperfusion-induced mitochondrial apoptosis. Global brain ischemia was induced by permanent occlusion of vertebral arteries and temporal occlusion of carotid arteries for 15 min. Rats were preconditioned by 5 min of sub-lethal ischemia and 2 days later 15 min of lethal ischemia was induced. With respect to mitochondrial apoptosis initiation, translocation of p53 to mitochondria was observed in hippocampus but not in cerebral cortex. However, level of both apoptotic bax and anti-apoptotic bcl-xl in both hippocampal and cortical mitochondria was unchanged after global brain ischemia. Detection of genomic DNA fragmentation as well as Fluoro-Jade C staining showed that ischemia induces apoptosis in vulnerable CA1 layer of rat hippocampus. IPC abolished completely ischemia-induced translocation of p53 to mitochondria and had significant protective effect on ischemia-induced DNA fragmentation. In addition, significant decrease of Fluoro-Jade C positive cells was observed as well. Our results indicate that IPC abolished almost completely both initiation and execution of mitochondrial apoptosis induced by global brain ischemia.