The Expression of Cyclins in Neurons of Rats after Focal Cerebral Ischemia

The change of the expression of Cyclins in neurons of rats after focal cerebral ischemia was investigated. Ischemia was induced by temporary middle cerebral artery occlusion （MCAO）. The experimental rats induced by MCAO were sacrificed on 7th and 14th day after reperfusion. The brain was taken out at 7th and 14th day after injury, and the expression of Cyclin D1, E, A and B1 in neurons of cerebral cortex or hippocampal CA1 region was detected by immunofluorescence and confocal microscope. The results showed that after MCAO, in the ipsilateral CA1 subfield of hippocampus the expression of Cyclin D1, E, A and B1 in neurons was significantly gradually up-regulated at 7th and 14th day after reperfusion （P〈0.05） as compared with that in control group. In the ipsilateral cerebral cortex the expression of Cyclin D1 and B1 in neurons was notably gradually down-regulated at 7th and 14th day, and that of Cyclin E and A was significantly up-regulated at 14th day after reperfusion as compared with that in control group （all P〈0.05）. It was concluded that there was a differential sensitivity among neurons from different brain regions to ischemic injury. But all of them re-enter into cell cycle after MCAO.     

Effect of Xingnaojing Injection (醒脑静注射液) on Hippocampal N-methyl-D-aspartic Acid Receptors of Focal Cerebral Ischemia in Rats

Objective: To observe and elucidate the neuroprotective effect of Xingnaojing (XNJ) injection on hippocampal N-methyl-D-aspartic acid (NMDA) receptors of focal cerebral ischemia in rats. Methods: Cerebral ischemia was established by occluding the middle cerebral artery with an intraluminal suture technique in rats. Neurological deficit score, infarct volume and quantity of NMDA receptors were estimated in all groups and compared. Results: After being treated with XNJ, the score decreased in the initial 6 hours and infarct volume decreased in 24 hours. And within 24 hours, the quantity of NMDA receptors obviously decreased compared with the model group (P<0. 01) It indicated that XNJ could ameliorate neurological behavior of middle cerebral artery occlusion rats and down-regulate the expression of hippocampal NMDA receptors. Conclusion: The neuroprotective effect of XNJ on focal cerebral ischemia is possibly related to down-regulating the expression of NMDA receptors in rats.     

Effect of Batroxobin on Neuronal Apoptosis During Focal Cerebral Ischemia and Reperfusion in Rats

We have found that Batroxobin plays a protactive role in ischemic brain injury,which attracted us toinvestigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion.The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method ofTdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis ofneurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models(n=18).The results showed that few scattered apoptosis cells were observed in right cerebralhemispheres after LMCA occlusion and reperfusion,and that a lot of apoptosis cells were found in leftischemic cortex and caudoputamen at 12h reperfusion,and they reached peak at 24h～48h reperfusion.However,in the rats pretreated with Batroxobin,the number of apoptosis cells in left cerebral cortexand caudoputamen reduced significantly and the neuronal damage was much milder at 24h reperfusionthan that of saline-treated rats.The results indicate that administration of Batroxobin may reduce theapoptosis of neurons induced by cerebral ischemia and reperfusion and afford significantcerebroprotection in the model of focal cerebral ischemia and reperfusion.     

Effects of Scalp Acupuncture on Focal Cerebral Ischemia in Rats

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Influence of Electroacupuncture on the mRNA of Heat Shock Protein 70 and 90 in Brain after Cerebral Ischemia/Reperfusion of Rats

To explore the anti-apoptotic role of electroacupuncture (EA) and its molecular mecha-nisms after cerebral ischemia/reperfusion (IR) of rats, by using animal model of middle cerebralartery occlusion (MCAO), the changes of the cleavage of PARP were observed by Western blot andthe mRNA of heat shock protein (Hsp) 70 and Hsp90β detected by competitive RT-PCR after cere-bral IR and EA treatment. The results were as follows: (1) The cleavage of PARP was increased inischemic hippocampus, and EA treatment could attenuate the level of the cleavage remarkably; (2)The mRNA expression of Hsp70 was increased in the ischemic cortex and hippocampus and was fur-ther increased after EA treatment; (3) The mRNA expression of Hsp90β was decreased in ischemiccortex and hippocampus and the decrease was relatively slight after EA treatment. The above resultsdemonstrated EA treatment could protect neurons from apoptosis after cerebral IR. One of the molec-ular mechanisms was the promotion of the inducible expression of Hsp7     

Effect of Rosiglitazone Maleate on Inflammation Following Cerebral Ischemia/Reperfusion in Rats

In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5, 2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion, respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and inter- leukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swell- ing (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflam- matory response after ischemia-reperfusion in this model.     

Effect of Electroacupuncture on Expression of p53 Protein in Cerebral Cortex of Rats with Global Cerebral Ischemia/Reperfusion Injury

Objective: To observe the effect of electroacupuncture (EA) on expression of p53 protein in cerebral cortex of senile rats with global cerebral ischemia/reperfusion (IR) injury and to explore its mechanism. Methods: The cerebral IR injury rat model was established referring to Pulsinelli 4-vessel occlusion method. Thirty-six SD rats were randomly and evenly divided into the control group, the IR group and the IR plus EA (IR-EA) group. The animals in the control group were subjected to electrocauterization of vertebral arteries in bilateral flank orifice alone with the general carotid arteries unoccluded. To rats in the IR-EA group, immediately and 24h, 48h, 72h after cerebral IR, EA treatment on bilateral acupoint "Zusanli" (ST36) was applied once a day, lasting for 60 minutes. After the final treatment, all the rats were sacrificed and their brains were taken to examine p53 protein expression by the immunohistochemical method. Results: Cells with positive p53 immunoreactivity in the cerebral cortex of     

An Early Continuous Experimental Study on Magnetic Resonance Diffusion-weighted Image of Focal Cerebral Ischemia and Reperfusion in Rats

Summary： The chronological and spatial rules of changes during focal cerebral ischemia and reperfusion in different brain regions with magnetic resonance diffusion-weighted imaging （DWI） in a model of occlusion of middle cerebral artery （MCAO） and the development of cytotoxic edema in acute phase were explored. Fifteen healthy S-D rats with MCA occluded by thread-emboli were randomly divided into three groups. 15 min after the operation, the serial imaging was scanned on DWI for the three groups. The relative mean signal intensity （RMSI） of the frontal lobe, parietal lobe, lateral cauda-putamen, medial cauda-putamen and the volume of regions of hyperintense signal on DWI were calculated. After the last DWI scanning, T2WI was performed for the three groups. After 15 rain ischemia, the rats was presented hyperintense signals on DWI. The regions of hyperintense signal were enlarged with prolonging ischemia time. The regions of hyperintense signal were back to normal after 60 min reperfusion with a small part remaining to show hyperintense signal. The RMSIs of parietal lobe and lateral cauda-putamen were higher than that of the frontal lobe and medial cauda-putamen both in ischemia phase and recanalization phase. The three groups were normal on T2WI imaging. DWI had good sensitivity to acute cerebral ischemia, which was used to study the chronological and spatial rules of development of early cell edema in ischemia regions.     

Changes of Nitric Oxide Synthase Activity in Penumbral and Core Area during Focal Cerebral Ischemia and Reperfusion in Rats

Objecivee: To study the changes of nitric oxide synthase (NOS) activity in penumbral and core area during focal cerebral ischemia and reperfusion, and to explore the therapeutic window of focal cerebral ischemia. Methods:The middle cerebral artery of rats was occluded for 15, 30,60,90 and 120 min by an inraluminal filament respectively,and recirculation was instituted for 24 h. The changes of NOS activity in ischemic core area(parietal cortex and caudoputamen) and penumbral area ( frontal cortex)were examined after focal cerebral ischemla and reperfusion using NADPH-d histochemistry, technique. Results. The NOS activity of the ischemic penumbral area peaked at 60 min while the ischemic core area peaked at 30 min then declined at 90-120 rain sharply. Conclusion: NOS takes part in cerebral ischemic damage during focal cerebral ischemia and reperfusion. The NOS activity of the ischemic penmnbral area is different from the ischemic core area. The peak time of the penumbral area is delayed comparing with the core area. The data suggest that the best time to apply NOS inhibitor is within 30 min in ischemic core area, and 60 rain in penumbral area.     

Involvement of Apoptosis in 3-nitropropionic Acid-induced Ischemicl Tolerance to Transient Focal Cerebral Ischemia in Rats

Preconditioningofbraintissueswithsub lethalstressesorstimulicanresultinresistancetosubse quentlethalischemiceventsinaresponsecalledis chemictolerance .Recently ,severalstudieshaveshownthatasinglesystemicdoseof 2 0mg/kg 3 NPAcausednohistopathologicalabnorm…     

三七总皂苷注射液对脑出血大鼠颅内血肿及脑水肿的影响

目的探讨三七总皂苷注射液对脑出血大鼠颅内血肿及脑水肿的影响。方法采用胶原酶法制备高血压脑出血动物模型。将60只大鼠随机分为假手术组、模型组及三七总皂苷高、中、低剂量组共5组,每组12只;造模后4h开始,每12h在颅内血肿内注射三七总皂苷注射液或生理盐水1次,共5次。于造模后24、72h测各组大鼠脑组织含水量,钠离子、钾离子含量。脑内血肿直径。结果三七总皂苷干预各组大鼠的神经缺损症状记分增加,差异具有统计学意义（P〈0．05）,出血侧皮质及基底节脑水含量及钠离子含量较模型组均增加;差异具有统计学意义（P〈0．05）,钾离子含量较模型组减低,差异具有统计学意Z（P〈0．05）;三七总皂苷各组治疗后血肿直径较脑出血模型组变小,差异具有统计学意义（均P〈0．05）。结论大量脑出血超早期给予三七总皂苷干预,有利于加速血肿的吸收,同时可加剧早期脑水肿,引起大鼠神经功能缺损计分增加。提示大量脑出血超早期应用三七总皂苷应慎重。     

大鼠局灶性脑缺血/再灌注后脑微血管中NO含量的动态变化

目的:探讨局灶性脑缺血/再灌注不同时相脑微血管及某些脑区中NO含量变化,为临床应用NO合酶抑制剂提供实验依据。方法:将Wister大鼠随机分为假手术（S）、缺血（I）和再灌注（R）3大组。采用线栓法造成大鼠右侧大脑中动脉阻塞的局灶性脑缺血/再灌注模型。以蛋白漂洗法提取大鼠右侧大脑皮层的脑微血管,Lowry法测定蛋白含量。荧光分光光度法测定NO含量。结果:脑缺血不同时相脑微血管中NO含量呈渐进性升高（I1、I4、I8组与S组比较,P<0.01）,I24组虽较S组略有升高,但无统计学差异;在纹状体与海马,除I1与I8外,其余各组均显著下降（P<0.01）;再灌注不同时相脑微血管中除I1R23组显著升高（P<0.01）外,其余两组无明显变化;在脑区,无论纹状体与海马,均显著下降（P<0.01）。结论:在局灶性脑缺血/再灌注不同时相、不同部位,其NO含量变化不同,提示NO参与局灶性脑缺血/再灌注的病理生理过程。     

血塞通注射液联合常规疗法治疗脑梗死的临床观察

目的 观察血塞通注射液联合常规疗法治疗脑梗死的临床疗效。方法 将122例脑梗死患者随机分为治疗组（62例）和对照组（60例）,两组均给予常规综合治疗（胞二磷胆碱静滴,口服肠溶阿司匹林片、都可喜、维生素等）和对症支持治疗,治疗组加用血塞通注射液（主要组分为三七总皂苷）400 mg,每天1次,共治疗14 d。结果 治疗组神经功能缺损改善优于对照组,总有效率达93.5%,明显高于对照组（75%）。结论 血塞通注射液联合常规疗法能有效改善脑梗死患者神经功能,提高总有效率。     

肾上腺髓质素对大鼠局灶性脑缺血再灌注后脑组织的保护作用

目的探讨肾上腺髓质素与脑缺血再灌注损伤的关系。方法采用栓线法制成大鼠大脑中动脉缺血再灌注模型，阻断血流2h后进行再灌注。应用免痘组织化学染色法拴测不同时间段大鼠局灶性脑缺血再灌注后肾上腺髓质素的表达情况，并进行动态观察。结果正常大鼠脑内即有肾上腺髓质表达，假手术后肾上腺髓质素表达略有增加，但与正常对照组相比无明显差异，P〉0．05；大鼠脑缺血再灌注后肾上腺髓质素免疫阳性细胞增多，与正常对照组及假手术组相比差异显著，均P＜0．05；大鼠脑缺血再灌注后缺血侧既缺血对侧肾上腺髓质素免疫阳性知胞均增多，但以缺血侧区域增多最为明显，P〈0．05。动态观察发现，脑缺血再灌注2h后，肾上腺髓质素免痘阳性细胞即增多，缺血再灌注6h迭高峰，至1周左右仍明显增多。结论脑缺血再灌注后肾上腺髓质表达增强。     

脑心通胶囊对脑缺血再灌注损伤大鼠脑水肿作用及机制研究

目的观察脑心通胶囊对大鼠局灶性脑缺血再灌注损伤所致脑水肿、脑组织内组织髓过氧化物酶(MPO)活性以及细胞间黏附分子-1(ICAM-1)、血管细胞间黏附分子-1(VCAM-1)和E-选择素(E-selectin)表达的影响。方法线栓法制备大鼠大脑中动脉缺血/再灌注模型,观测脑心通胶囊对脑含水量、MPO活性以及ICAM-1、VCAM-1、E-selectin表达的影响。结果脑心通胶囊0.24、0.48 g/kg能减轻模型大鼠脑水肿,降低脑组织MPO活性,减少模型大鼠脑组织ICAM-1、VCAM-1、E-selectin的表达。结论脑心通胶囊对大鼠脑缺血再灌注损伤引起的脑水肿有保护作用,其作用机制与降低脑组织MPO活性、减少模型大鼠脑组织ICAM-1、VCAM-1、E-selectin的表达有关。     

一氧化氮在全脑缺血再灌注大鼠脑损害中的作用

目的　探讨一氧化氮在全脑缺血 2 0min后再灌注大鼠脑损害中的作用。方法　雄性Wistar大鼠 84只 ,体重 (2 2 0± 2 0 )g ,随机分为对照组 (12只 )和缺血组 (72只 ) ,后者设 8、2 4、48、72、96、16 8h 6个时相点。参照Pulsinelli等的方法制作大鼠全脑缺血 2 0min再灌注模型 ,于再灌注后 8、2 4、48、72、96、16 8h活杀取血及海马组织 ,对照组施行麻醉及手术 ,但不缺血 ,观察 72h后取血及海马组织 ,测定血清NSE、海马NO含量及海马CA1区锥体神经元 (Pyramidalneuron ,PN)密度。结果　①海马NO含量于缺血再灌注后 48h明显升高 ,72h达峰值 (与对照组比较P均 <0 .0 1) ,以后逐渐下降 (96h仍明显高于对照组水平 ,P <0 .0 5 ) ,16 8h降至接近对照组 ;②缺血组各时相点血清NSE含量均显著高于对照组 (P 均 <0 .0 1) ;③缺血组海马CA1区PN密度呈明显的逐渐减少趋势 ,自 48h后均明显低于对照组 (P均 <0 .0 1) ,再灌注后 16 8h仅为对照组水平的 2 2 .8% ;④缺血再灌注后海马NO含量与血清NSE水平的变化呈显著的线性正相关 (r =0 .90 2 2 ,P <0 .0 1)。结论　NO在全脑缺血再灌注损伤中起着重要作用 ,是引起海马CA1区锥体神经元DND发生的主要因素之一。     

猪胆酸对体外缺血再灌注大鼠脑微血管内皮细胞ICAM-1的影响

目的观察大鼠脑微血管内皮细胞缺血再灌注损伤细胞间黏附分子-1(ICAM-1)表达的影响,探讨清开灵有效组分猪胆酸阻抑脑缺血炎症反应的作用途径。方法体外培养大鼠脑微血管内皮细胞,氧糖剥夺法模拟缺血再灌注损伤,采用免疫细胞化学染色和RT-PCR方法半定量检测ICAM-1蛋白和mRNA的表达。结果与正常组比较,模型组ICAM-1蛋白和mRNA的表达明显增高(P<0.01);与模型组比,猪胆酸显著降低ICAM-1的表达(P<0.05)。结论猪胆酸可能通过干预ICAM-1表达而阻抑脑缺血损伤炎症反应。     

大鼠局灶性脑缺血再灌注损伤后Jak1的表达

目的　探讨Jak基因在大鼠局灶性脑缺血再灌注损伤中的表达及其在缺血性神经细胞损伤中的可能作用。方法采用线栓法制作大鼠局灶性脑缺血再灌注损伤的模型 ,用免疫组化方法观察Jak1蛋白在大鼠局灶性脑缺血再灌注损伤后不同时间点脑组织中的表达。结果脑缺血再灌注损伤后 12h在栓塞侧梗死区神经元可见少量Jak1蛋白阳性表达 ,2 4h达高峰。梗死周边区表达最显著 ,表达持续时间达 1周。结论Jak1在脑缺血后表达增加 ,表明Jak1可能参与了脑缺血神经细胞损伤与修复的病理过程。     

七叶皂苷钠对大鼠局灶性脑缺血损伤炎症反应的作用

目的：观察七叶皂苷钠对大鼠脑缺血再灌注损伤局部炎症反应的影响。方法：线栓法阻塞大鼠左侧大脑中动脉，建立缺血再灌注模型，经视交叉的冠状脑组织块行TTC染色测梗死面积，并进行髓过氧化物酶（myeloperoxidase,MPO)、细胞间黏附分子－1（inter-cellular adhesion molecule-1,ICAM-1)免疫组化染色。结果：再灌注即刻腹腔内注射七叶皂苷钠的治疗组较对照组神经功能缺损程度显著减轻（P＜0.05)，梗死面积明显缩小（P＜0.05)，MPO阳性细胞数明显减少（P＜0.05)，ICAM-1免疫阳性血管数无显著变化（P＞0.05)。结论：七叶皂苷钠对局灶性脑缺血损伤的保护作用可能与抑制局部炎性渗出有一定的关系。     

大鼠局灶性脑缺血再灌注时神经细胞凋亡的动态变化

目的:观察大鼠脑缺血再灌注后神经细胞凋亡的动态变化.方法:采用健康雄性大鼠大脑中动脉阻断(MCAO)模型,阻断大脑中动脉(MCA)血流2h后再灌注,在0.5h,6h,12h,24h和48h不同时间点断头取脑,连续取脑进行TuNEL染色。结果:①假手术组、缺血再灌注组非缺血侧大脑半球未见阳性的凋亡细胞。②脑缺血再灌注早期部分神经细胞发生了凋亡。随着再灌注时间的延长,凋亡细胞数目逐渐增多,12h～24h达到高峰。③凋亡细胞主要分布在梗死灶的边缘区,梗塞灶中心区和正常区无凋亡细胞。结论:神经细胞凋亡在脑缺血再灌注损伤时起着重要作用。