短暂局部预缺血对脑梗塞大鼠的影响及HSP70的表达

目的 建立局灶性可重复性大鼠脑缺血动物模型，研究短暂性局部脑缺血后再灌注不同时间对大脑中动脉闭塞(MCAO)的影响。方法 应用改进的Longa's法局灶性脑缺血模型，建立阻断左侧大脑中动脉的局部脑缺血预处理模型。各组大鼠均经两次处理，预处理(PC)组大鼠经15min短暂预缺血，分别在再灌注6、12、24、72、168h后(n=15～16)，造成MCAO；脑梗塞组大鼠只在第二次处理造成大脑中动脉闭塞；短暂缺血组只在第一次处理时缺血15min。各组大鼠均在第二次处理后24h，检测以下指标：神经功能缺失评分；TTC染色测量梗塞范围；HE染色，观察组织结构变化；干湿法测量脑水含量；免疫组织化学染色观察HSP70的表达。结果 PC24h、PC72h和PC 168h组与脑梗塞组相比较，脑梗塞范围、脑水肿的严重程度、梗塞周边区脑组织的缺血性损伤明显减轻了；短暂缺血引起了轻微的神经细胞结构的改变并使缺血区HSP70表达增加，MCAO后24hHSP70蛋白在缺血周边区出现广泛表达。结论 短暂局部缺血预处理可以诱导脑梗塞后脑组织产生缺血耐受性，其保护作用出现在再灌注后1～7d；缺血预处理引起HSP70蛋白表达的改变与缺血耐受的产生有一定联系.     

大鼠局灶缺血预处理诱导的脑缺血耐受中热休克蛋白70的表达及其意义

目的　研究局灶脑缺血预处理对热休克蛋白 70 (HSP70 )表达和脑缺血耐受的影响。方法　SD大鼠随机分为 3组 :预缺血组、假手术组及对照组 ,前两组分别在 2小时大脑中动脉缺血 (MCAO)前 3天给予10分钟的预缺血或假手术 ,MCAO后 2 4小时处死 ,对照组给予两次相隔 3天的假手术 ,比较各组梗死体积及HSP70的表达。结果　预缺血组梗死体积较假手术组减少 5 2 5 4 % (P <0 0 1) ,HSP70表达高于假手术组及对照组 (P <0 0 1)。结论　 10分钟大脑中动脉预缺血可有效诱导缺血耐受 ,增加HSP70表达。HSP70表达上调可能是局灶性脑缺血耐受产生的分子机制之一     

诱导缺血耐受的缺血预处理动物模型的建立

目的 :建立能诱导脑缺血耐受的缺血预处理SD大鼠模型。方法 :SD大鼠分别给予生理盐水右侧颈内动脉灌注 (SI)、双侧颈总动脉夹闭 (BCAO)和双侧颈总动脉夹闭并生理盐水右侧颈内动脉灌注 (BCAO +SI)预处理 ,每次持续 3min ,间隔 7min ,反复 3次 ,2 4h后作线栓大脑中动脉栓塞 (MCAO)。观察处理对MCAO缺血对侧肢体活动、脑组织含水量和梗死体积的影响。结果 :MCAO后 2 4h和 48hBCAO +SI预处理组神经损害体征和脑含水量较SI和BCAO两组轻 ;MCAO 72hBCAO +SI组脑梗死体积也低于其他两组。结论 :BCAO +SI预处理能诱导脑组织明显缺血耐受 ,是研究缺血耐受机制比较理想的缺血预处理模型     

丁苯酞对大鼠脑缺血再灌注损伤后HSP10表达的影响

目的研究丁苯酞干预对大鼠脑缺血再灌注损伤后不同时点脑组织中热休克蛋白10(HSP10)表达的影响,并探讨丁苯酞对缺血性脑血管病保护作用的机制。方法采用夹闭双侧颈总动脉的方法制作大鼠前脑缺血再灌注模型;H&E染色和NSE免疫组化染色神经元,观察脑组织的形态变化和记数各组神经元数目;免疫组织化学检测对照组、缺血再灌注组及丁苯酞干预组大鼠脑组织HSP10的表达水平变化。结果脑缺血再灌注后丁苯酞干预组及缺血再灌注组HSP10表达水平于再灌注后6h开始上调,3d达到高峰,丁苯酞干预组各时间点HSP10阳性表达指数均高于缺血再灌注组,丁苯酞干预组脑组织的损伤程度明显轻于脑缺血再灌注组(P<0.05)。结论丁苯酞可能通过上调大鼠缺血再灌注损伤后脑组织HSP10的表达,从而抑制前脑缺血再灌注损伤后细胞凋亡,减少神经元死亡,减轻缺血再灌注后脑组织的损伤。     

丁苯酞预处理对脑缺血再灌注大鼠内质网应激的影响

目的 探讨丁苯酞预处理对脑缺血再灌注大鼠内质网应激的影响.方法 30只SD大鼠随机分成假手术组、缺血再灌注组、丁苯酞预处理组,每组10只大鼠.丁苯酞预处理组大鼠给予丁苯酞80 mg/kg灌胃,1次/d;缺血再灌注组和假手术组大鼠给予等量生理盐水替代.灌胃7d后,采用Zea Longa法制备大鼠脑缺血再灌注模型.假手术组不插入线栓.采用TTC染色检测脑梗死面积;RT-PCR法测定脑组织葡萄糖调控蛋白78(GRP78) mRNA、C/EBP同源蛋白(CHOP) mRNA的表达.结果 假手术组大鼠脑组织未见梗死灶;丁苯酞预处理组大鼠脑梗死面积明显小于缺血再灌注组(P＜0.05).缺血再灌注组和丁苯酞预处理组大鼠脑组织GRP78 mRNA、CHOP mRNA的表达量明显高于假手术组(均P＜0.05);丁苯酞预处理组大鼠脑组织GRP78 mRNA、CHOP mRNA的表达量明显低于缺血再灌注组(均P＜0.05).结论 丁苯酞可能通过抑制内质网应激而起到脑保护作用.     

电针预处理对大鼠脑缺血再灌注损伤后EAAT2的表达研究

目的研究电针预处理对脑缺血再灌注损伤后大鼠缺血半暗带兴奋性谷氨酸转运体2(EAAT2)表达的影响,探讨EAAT2在电针预处理诱导脑缺血耐受中的作用。方法 18只SD雄性大鼠随机分为3组(n=6):分别为假手术(Sham)组、右侧大脑中动脉阻闭(MCAO)组、电针预处理(EA)组。假手术组仅分离血管,不进行阻闭,术后24 h检测;MCAO组用MCAO法致缺血120 min后于再灌注24 h检测;EA组大鼠予电针刺激30 min,刺激结束2 h后处理同MCAO组。3组大鼠在观察神经行为学变化后取材,通过2,3,5-氯化三苯四唑(TTC)染色评估梗死面积,并检测EAAT2 mRNA及蛋白表达水平。结果电针预处理能明显降低脑梗死容积百分比(P0.01),提高MCAO大鼠神经行为学评分,诱导脑缺血耐受并抑制脑缺血再灌注损伤后24 h EAAT2表达的下降(P0.01)。结论脑缺血再灌注损伤后,EAAT2表达下降,而电针预处理能显著抑制缺血半暗带EAAT2的表达下调,诱导脑缺血耐受,从而减轻脑缺血再灌注损伤。     

秋水仙碱联合环磷酰胺增强大鼠脑缺血耐受的作用及其对热休克蛋白70表达的影响

目的　观察环磷酰胺联合秋水仙碱对预缺血诱导的脑缺血耐受及热休克蛋白 70 (HSP70 )表达的影响。方法　SD大鼠随机分为药物、预缺血及假手术 3个组 ,分别在 2小时大脑中动脉缺血 (MCAO)前 3天给予 10分钟的预处理、药物加预处理或假手术 ,MCAO后 2 4小时处死 ,比较各组神经功能评分、梗死体积及HSP70的表达。结果　药物组神经功能缺损减轻和梗死体积缩小较预缺血组更为明显 ,HSP70表达亦高于其余两组 (P <0 0 1)。结论　环磷酰胺联合秋水仙碱可增强预缺血诱导的脑缺血耐受作用 ,上调HSP70表达 ,二者具有叠加效应。     

局灶预缺血诱导脑缺血耐受的动物模型

目的　建立一种简便可靠的 SD大鼠局灶性脑缺血预处理模型。方法　将大鼠随机分为 3组 ,分别给予 10 m in大脑中动脉缺血 ( MCAO)预处理 ( PC) ;10 min PC后 2 h MCAO( PC MCAO)及假手术 ( SS)后 2 hMCAO( SS MCAO) ,再灌注 2 2 h后处死 ,观察各组神经功能缺损、梗死体积及脑含水量变化。结果　 PC MCAO组神经功能评分、梗死体积及含水量均明显低于 SS MCAO组 ,PC组无神经功能缺损及梗死灶形成。结论　 2次线栓法建立的大鼠局灶脑缺血预处理模型 ,能有效减轻 MCAO所致的神经损伤 ,操作简便 ,稳定性好 ,是一种研究局灶脑缺血耐受的有用工具。     

低氧预处理对大鼠脑缺血再灌注后梗死体积和血脑屏障通透性的影响

目的　探讨低氧预处理对大鼠脑缺血再灌注损伤的保护作用。方法　将SD大鼠分为 3组 ,即假手术组、缺血再灌注组、缺氧预处理 +缺血再灌注组。连续吸入 8%O2 +92 %N2 3h作缺氧预处理 ,12h后再经插线左大脑中动脉栓塞 (MCAO)制作缺血再灌注模型 ,到相应时间点后观察缺氧预处理对MCAO大鼠的行为、脑含水量、血脑屏障通透性和脑梗死体积的影响。结果与缺血再灌注组相比 ,缺氧预处理组大鼠的行为明显改善 ,脑伊文思蓝 (EB)含量、脑含水量 (P <0 0 5 ) ,脑梗死体积缩小。结论　低氧预处理降低缺血再灌注脑组织血脑屏障通透性 ,抑制脑水肿 ,缩小梗死体积 ,对缺血再灌注损伤具有保护作用     

丁苯酞预处理对大鼠脑缺血再灌注损伤的神经保护作用

目的研究丁苯酞预处理对大鼠局灶性脑缺血再灌注损伤的神经保护作用。方法健康成年SD雄性大鼠48只,随机分为假手术组、缺血再灌注组、丁苯酞预处理组,每组各16只。各组均灌胃5d后,采用线栓法制作大鼠局灶性脑缺血再灌注(MCAO)模型,缺血2h、再灌注24h,进行神经功能缺损评分,TTC染色及图像分析观察脑梗死体积,免疫组化法检测脑组织caspase-3、bcl-2表达的变化。结果与缺血再灌注组相比,丁苯酞预处理组神经缺损程度改善,梗死灶体积减少,caspase-3阳性细胞数量减少,bcl-2表达上调。结论丁苯酞可减轻缺血性脑血管病的发作,具有一定的神经保护作用。     

脑缺血预处理及HSP70表达对大鼠脑梗死的保护作用

目的建立局灶性可重复性大鼠脑缺血动物模型,探讨蛋白合成在脑缺血预处理(PC)诱导脑缺血耐受(IT)中的作用。方法应用改进的Longa’s法建立局灶脑缺血(MCAO)模型,短暂性脑缺血20min作为PC,PC 后24h给予永久性MCAO(PMCAO),并与未进行PC者比较。免疫印记法测量PC后24h及给予蛋白合成抑制剂放线菌酮后HSP70的变化,PMCAO24h后观察脑梗死的大小,神经功能评分;同时观察在PC前或PC后PMCAO 前给予蛋白合成抑制剂放线菌酮对上述指标的影响。结果 PC后24h行PMCAO,脑梗死体积明显减小(P<0．01), 神经功能评分减低(P<0．05);PC前给予放线菌酮消除了以上影响,但在PC后较长时间而在PMCAO之前给予则没有以上影响;HSP70在PC后24h明显表达,而在PC前30min给予防线菌酮抑制了HSP70的表达。结论 PC能够通过减少脑组织损伤和神经功能缺损对之后发生的脑缺血产生脑保护作用。PC诱导脑缺血耐受有赖于新蛋白的合成。     

缺血预处理（IPC）对大鼠局灶性脑梗死后HSP70和FOS表达的影响

目的 :研究缺血预处理 (IPC)对局灶性脑梗死后HSP70和FOS表达的影响 ,探讨IPC的脑保护作用机制。方法 :利用线栓法建立局灶性脑缺血 大脑中动脉闭塞模型 (MCAO)。MCAO 10min作为IPC ,IPC后 48h制作永久性大脑中动脉梗死 (PMCAO)模型。了解IPC对PMCAO后大脑神经功能和脑组织学损害的影响 ,免疫组化法研究PMCAO后 3hFOS表达变化以及 2 4h后HSP 70表达变化。结果 :IPC显著减轻PMCAO后大鼠神经功能损害和组织学损害 ,减少PMCAO后FOS、HSP 70的表达。结论 :IPC对其后PMCAO有明显的保护作用 ,能诱导脑缺血耐受 (IT)的产生 ,脑IT的神经保护作用与脑梗死后HSP 70和FOS表达改变密切相关。     

局灶性脑缺血耐受和星形胶质细胞反应

目的　研究短暂性局灶性脑缺血预处理对永久性局灶性脑缺血的保护作用 ,及最佳预处理时间剂量 ,并探讨星形胶质细胞在脑缺血耐受中的反应。方法　采用开颅方法阻断大鼠大脑中动脉 ,通过观察大鼠脑梗死后神经功能损伤状况、脑梗死体积分析及病理形态学变化 ,评价不同的缺血预处理时间剂量 (10分钟、2 0分钟、30分钟 )对永久性局灶性脑缺血的保护作用。采用胶质纤维酸性蛋白 (GFAP)免疫组化法观察星形胶质细胞在脑缺血耐受中的反应。结果　与对照组相比 ,缺血预处理 2 0分钟未引起明显的神经元损伤 ,但使永久性局灶性脑缺血后神经功能损伤减轻 ,梗死体积明显减小 (P <0 .0 1)。免疫组化显示 ,2 0分钟缺血预处理组及重复缺血组星形胶质细胞在损伤预处理侧广泛激活。结论　 2 0分钟局灶性脑缺血预处理能够有效诱导脑缺血耐受。星形胶质细胞的激活可能与脑缺血耐受中神经元的存活相关。     

Sustained blockade of brain AT1 receptors before and after focal cerebral ischemia alleviates neurologic deficits and reduces neuronal injury, apoptosis, and inflammatory responses in the rat.

In the present study, we investigate whether a long-term blockade of brain AT1 receptors in male Wistar rats before and after ischemic injury exerts neuroprotective effects and modulates apoptosis and inflammatory responses, which are associated with the post-ischemic progression of brain damage. The AT1 receptor antagonist irbesartan was continuously infused intracerebroventricularly using osmotic minipumps over a 5-day period before and for 3 or 7 days after middle cerebral artery occlusion (MCAO) for 90 minutes. Neurologic status was evaluated daily, starting 24 hours after MCAO. After MCAO (3 and 7 days), brains were removed for the measurement of infarct size and immunohistochemical evaluation of apoptosis and accumulation of reactive microglia and macrophages. Treatment with irbesartan before ischemia improved motor functions, whereas post-ischemic treatment improved sensory functions. Blockade of brain AT1 receptors reduced the infarct size on days 3 and 7 after MCAO. In the peri-infarct cortex, irbesartan treatment decreased the number of apoptotic cells on day 3 and attenuated the invasion of activated microg-lia and macrophages on days 3 and 7 after ischemia. Long-term blockade of brain AT1 receptors improves the recovery from cerebral ischemia. Antiapoptotic mechanisms and inhibition of post-ischemic inflammation are involved in the AT1 receptor blockade-induced neuroprotective effects in ischemic brain tissue.     

Expression of endothelial nitric oxide synthase in the ischemic penumbra: relationship to expression of neuronal nitric oxide synthase and vascular endothelial growth factor

Expressional patterns of the endothelial and neuronal forms of nitric oxide synthase (NOS) in cerebral ischemia were studied utilizing a permanent middle cerebral artery occlusion (PMCAO) model. Motor performance and infarct volumes were determined in the rats. Immunohistochemical staining for eNOS, nNOS and neurofilament were performed at 1, 2, 3, 5, 7 and 14 days after PMCAO. Vascular endothelial growth factor (VEGF) expression was determined by in-situ hybridization. PMCAO caused a reproducible cortical infarct with motor deficits in the rats. Double immunohistochemical stainings indicated that eNOS and nNOS were induced in ischemic neurons. Most stained neurons were positive for both NOS forms but some reacted with only one NOS antibody. nNOS expression peaked at 24-48 h after PMCAO, stained mainly the cytoplasm of core neurons, and disappeared after the 3rd day. eNOS expression increased until the 7th day, stained mainly the cytoplasm and membrane of penumbral cells and disappeared by the 14th day after PMCAO. VEGF expression was significantly induced in the penumbral zone in a similar distribution to eNOS. The anatomical and temporal pattern of VEGF and eNOS induction in the brain after permanent ischemia suggest that these mediators may play a role in protecting penumbral tissue from additional ischemic damage.     

Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat

Abstract

The selectin family of adhesion molecules is involved in adhesion of leukocyte to microcirculatory system and the transmigration into brain parenchyma. Although the role of P-selectin may be important in the pathogenesis of brain ischemia, a possible protective effect on ischemic brain injury by blocking P-selectin has not been reported. We have examined the effects of a novel anti-P-selectin antibody on ischemic brain injury after 24 h of permanent middle cerebral artery occlusion (MCAO) in rat. Male Wistar rats were subjected to MCAO by an insertion of a silicone rubber cylinder for 24 h. Anti-rat P-selectin monoclonal antibody, ARP 2-4 was injected intravenously at a dose of 1 mg kg^–1 at 5 min before the induction of MCAO. Control animals received the same volume of vehicle solution. Regional cerebral blood flow (rCBF) was measured immediately after and at 8 h of MCAO. At decapitation of rats at 24 h of permanent MCAO, infarct size was compared between the antibody and vehicle treated group. In addition, immunohisto- chemistry for leukocyte infiltration and HSP72, and histochemistry for TUNEL were also compared. Pretreatment with ARP 2-4 improved rCBF at 8 h of MCAO (55.4% ± 11.7% of control, n = 5) as compared to vehicle group (24.2% ± 77.8%, n = 5, p < 0.02). Although leukocyte infiltration was not normally detected by monoclonal antibodies for CD11a and CD18, it became remarkably evident at 7 day of MCAO. Although HSP72 and TUNEL were not also detected in sham control brains, they were induced in neurons of the MCA area at 7 day of MCAO. Treatment with ARP 2-4 significantly reduced the numbers of leukocyte and neurons with positive HSP72 and TUNEL stainings. These results demonstrated that an administration of a monoclonal antibody against P-selectin improved rCBF, and attenuated infarct size that was associated with reduction of leukocyte infiltration. Furthermore, treatment with the antibody reduced both HSP72 and TUNEL stainings. These data suggest an important role of P-selectin in ischemic brain damage, and a future therapeutic potential to human stroke patients. [Neurol Res 1999; 21: 269-276]     

Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat.

The selectin family of adhesion molecules is involved in adhesion of leukocyte to microcirculatory system and the transmigration into brain parenchyma. Although the role of P-selectin may be important in the pathogenesis of brain ischemia, a possible protective effect on ischemic brain injury by blocking P-selectin has not been reported. We have examined the effects of a novel anti-P-selectin antibody on ischemic brain injury after 24 h of permanent middle cerebral artery occlusion (MCAO) in rat. Male Wistar rats were subjected to MCAO by an insertion of a silicone rubber cylinder for 24 h. Anti-rat P-selectin monoclonal antibody, ARP 2-4, was injected intravenously at a dose of 1 mg kg-1 at 5 min before the induction of MCAO. Control animals received the same volume of vehicle solution. Regional cerebral blood flow (rCBF) was measured immediately after and at 8 h of MCAO. At decapitation of rats at 24 h of permanent MCAO, infarct size was compared between the antibody and vehicle treated group. In addition, immunohistochemistry for leukocyte infiltration and HSP72, and histochemistry for TUNEL were also, compared. Pretreatment with ARP 2-4 improved rCBF at 8 h of MCAO (55.4% +/- 11.7% of control, n = 5) as compared to vehicle group (24.2% +/- 11.8%, n = 5, p < 0.02). Although leukocyte infiltration was not normally detected by monoclonal antibodies for CD11a and CD18, it became remarkably evident at 1 day of MCAO. Although HSP72 and TUNEL were not also detected in sham control brains, they were induced in neurons of the MCA area at 1 day of MCAO. Treatment with ARP 2-4 significantly reduced the numbers of leukocyte and neurons with positive HSP72 and TUNEL stainings. These results demonstrated that an administration of a monoclonal antibody against P-selectin improved rCBF, and attenuated infarct size that was associated with reduction of leukocyte infiltration. Furthermore, treatment with the antibody reduced both HSP72 and TUNEL stainings. These data suggest an important role of P-selectin in ischemic brain damage, and a future therapeutic potential to human stroke patients.     

脑缺血再灌注后热休克蛋白70、c-fos的表达及柘树制剂的神经保护作用

目的 观察局灶脑缺血再灌注后热休克蛋白（HSP）70、c-fos的表达及其与细胞调亡的关系,探讨柘树制剂对脑缺血后神经细胞损伤的保护作用。方法 采用改良Longa法制作大鼠局灶脑缺血冉灌注模型。柘树制剂预处理组（柘树组）大鼠在实验前灌服柘树制剂2ml每日3次,连用5d。在缺血再灌注不同时点（1h、6h、12h、24h、3d、7d）将大鼠处死取腑,进行HSP70及c-fos免疫组化染色、c-fos mRNA原位杂交、原位末端标记（TUNEL）及HE染色,许对其阳性结果进行半定量分析。结果脑缺血再灌注能诱导HSP70及c-fos的表达。缺血冉灌注6h绀HSP70存缺血侧皮质及基底节开始表达,24h达高峰。缺血再灌注1h组c-fos即有表达,6h达高峰,后逐渐下降。细胞凋亡于缺血再灌注6h最显著。柘树组HSP70及c-fos表达的阳性细胞数均较缺血再灌注组明监增加,两组比较差异均有显著性（均P〈0．01）,而TUNEL阳性细胞数明显减少。结论 HSP70及c=-ros均参与了脑缺血的病理生理过程,柘树制剂对脑缺吡冉灌注损伤有保护作用。     

The effect of ECr on HSP70 expression and morphologic changes following transient cerebral lschemia in rats

OBJECTIVE To investigate the effect of Cudrania tricuspidata root extract (ECr) on ischemic cerebral damage and the expression of the 70KDa heat shock protein (HSP70) following transient focal ischemia. BACKGROUND The role that ECr plays in cerebral ischemia has not been studied. METHODS Healthy wistar rats were randomized to the normal control group(Group A,n=4),the sham-operated control group(Group B,n=4),the ischemia and reperfusion group (Group C,n=24),the ischemia and reperfiusion after ECr pre- administration group(Group D,n=24).The rats of Group C and Group D were subjected to transient left middle cerebral artery occlusion (MCAO)as described by Zea Longa for 1 hour. Brain sections at the level of striatum were performed for HSP70 immunohistochemistry and morphology.HSP70 positive reactions and morphologic changes were semiquantiratively analyzedl. RESLULTS In the rats of Group A and Group B, there were scarcely HSP70 immunoreactivities either in cortex or in striatal neurons. In the ischemic brain regions for Group C rats,the HSP70 was induced in morphologically intact neurons and endothelial cells at hour 6 after recirculation, increased at hour12,peaked at day I, decreased at day 3,and HSP70 expression only occured in endothelial cells at day7. In Group D rats, the HSP70 was induced in the neurons of left MCA distribution at hour 1 after reperfusion, The changes in expression of HSP70 at different time points in Group D rats was in accord whth in Group C, but the number of HSP70 positive cells in Group D increased more, and HSP70 irnmunoreactivity in the HSP70-postive cells were more intense than in Group C. Histopathological study with HE staining showed no neuron pyknosis in Group A or in Group B. While pykrotic cells were present in the ipsilateral cortex and striatal neurons of MCA territory of Group C rats beginning at 6 hours after roper fusion. The change of histopathology in Group D was lighter at every time point. The number of pyknotic neurons in left MCA distribution was less than in Group C and there was no evident cell damage at 3 days and 7 days of reperfusion in Group D rats. CONCLUSION Our study demonstrated that transient focal cerebral ischenia could induce the HSP70 expression and induce neurons pyknosis.While ECr pre-treatment before transient focal ischemia in rats could increase the expression of HSP70 and reduce neuronal injury. These data suggests that might be able to enhance neuronal ischemic tolerance of the rats and might have prophylactic neuroprotective effect on ischemic cerebral damage in rats.