反复性脑缺血大脑皮质LTC_4、cAMP和OFR的代谢变化

目的：研究反复脑缺血大脑皮质白三烯（ＬＴＣ４）、环腺苷酸（ｃＡＭＰ）和氧自由基（ＯＦＲ）的代谢变化与神经元损伤的关系。方法：对比观察大鼠反复性与单次性脑缺血大脑皮质ＬＴＣ４、ｃＡＭＰ、超氧化物歧化酶（ＳＯＤ）和丙二醛（ＭＤＡ）的含量变化及相应的病理改变。结果：反复缺血及再灌流早期ＬＴＣ１、ｃＡＭＰ的含量明显升高,ＳＯＤ活性显著降低,ＭＤＡ延迟性持续显著增高,皮质神经元损害显著重于单次缺血组。结论：ＬＴＣ４、ｃＡＭＰ和 ＯＦＲ均参与了反复缺血性脑损害的病理机制,可能与 Ｃａ＋＋介导的花生四烯酸（ＡＡ）瀑布效应有关。     

大鼠实验性短暂脑缺血血浆中cAMP相对浓度与血脑屏障变化之关系

目的观察短暂脑缺血再灌流过程中血脑屏障超微结构及血浆中环腺苷酸（ｃＡＭＰ）相对浓度的变化。方法用改良ｐｕｌｓｉｎｅｌｉ法造成短暂脑缺血再灌流模型。用Ｈ３－ｃＡＭＰ放免分析药盒测定血浆中ｃＡＭＰ相对浓度,并观察血脑屏障中紧密连接的变化。结果在短暂缺血及再灌流早期,血浆中ｃＡＭＰ相对浓度及紧密连接紧密程度（闭锁小带长度、凸嵴数目）无明显变化,血管内皮中胞饮小泡数目明显增多。再灌注中期内皮细胞间紧密连接松弛,闭锁小带长度及凸嵴数目均减少。血浆中ｃＡＭＰ浓度亦降低。结论短暂脑缺血及再灌流早期血脑屏障通透性的改变,主要是由于内皮细胞中胞饮小泡数增多所致。血浆中ｃＡＭＰ相对浓度可以反映血脑屏障的开放程度。     

实验性脑缺血组织自由基水平,神经病理与甘露醇作用机制的…

以家兔急性不完全性脑缺血模型，采用“电子自旋共振波谱技术及电子显微镜，对实验性服缺血组织自由基水平及神经病理进行研究，同时对甘露醇的作用机制进行探讨。结果证实，脑血后自由基水平明显增高，神经细胞、星形胶质细胞超微结构发生明显病理改变。而经甘露醇治疗后，自由基水平显著下降，与模型组比较，Ｐ〈０．０１；且大脑皮层细胞损伤程度较模型组明显减轻。这种抑制生组织损伤的作用与甘露醇清除自由基功能及高渗作用密切     

脑缺血小鼠额叶皮层和海马组织cAMP水平的变化

目的观测缺血性小鼠额叶皮层和海马组织环磷酸腺苷（cAMP）水平，探讨脑缺血发病的分子生物学机制。方法通过双侧颈总动脉线结、连续3次缺血一再灌注制作脑缺血动物模型。并设立假手术组；术后29、30d分别测试学习和记忆成绩；应用放射免疫法检测小鼠额叶皮层和海马组织cAMP水平。结果与假手术组比较，模型组学习和记忆成绩均降低（P〈0．05），且额叶皮层和海马组织cAMP水平也降低（P〈0．05）。结论额叶皮层和海马组织cAMP水平降低可能参与了脑缺血的分子生物学发病机制。     

短暂脑缺血再灌注后大鼠大脑皮质ATP含量的动态变化

目的　探讨短暂脑缺血再灌注后大鼠大脑皮质ATP含量的动态变化及其与神经功能恢复之间的关系。方法　采用线栓法建立大鼠大脑中动脉闭塞 (MCAO)模型 ,缺血 10min后于再灌注后 0h、1h、3h、6h、12h、2 4h和 72h应用毛细血管电泳法分别测定额顶叶皮质的ATP含量 ,观察其变化规律。结果　缺血 10min后额顶叶皮质ATP的含量急剧下降至对照组的 2 0 %。再灌注后ATP的含量逐渐恢复 ,于再灌注后 1h、3h、6h和 12h恢复至对照组的 70 .5 %、6 5 .7%、84 .8%和 86 .9%。再灌注后 2 4hATP含量再次下降 ,再灌注后2 4h和 72hATP含量仅为对照组的 5 0 % ,与对照组相比差异均有显著性 (P <0 0 1,P <0 0 5 )。缺血 10min再灌注后大鼠肢体功能可逐渐恢复 ,但再灌注后 2 4h起出现不愿活动和进食等表现。结论　短暂脑缺血再灌注后大鼠额顶叶皮质存在细胞能量系统功能恢复滞后的现象。同时 ,随着再灌注的进行还出现了继发性细胞能量系统功能衰竭的现象 ,这可能与脑缺血再灌注后的神经功能延迟恢复有关     

脑缺血早期大脑皮质区神经元内一氧化氮合酶活性的变化

建立大鼠ＭＣＡＯ局灶脑缺血模型,利用ＮＡＤＰＨ－ｄ组织化学方法检测脑缺血早期大脑皮质缺血区神经元内一氧化氮合酶活性的变化。结果显示脑缺血早期３０ｍｉｎ神经元内一氧化氮合酶活性开始至高峰,随后下降,脑缺血后６０ｍｉｎ,降至正常。     

脑梗塞患者血浆及脑缺血鼠脑组织儿茶酚胺含量的变化

目的 研究脑梗塞患者及脑血鼠脑组织茶酚胺（ＣＡ）浓度变化,和其在脑缺血损伤中的作用以及与脑梗塞患者的有现的关系,方法 采用液相色谱－电化学检测器方法测定了３９例脑梗塞患者血浆ＣＡ浓度和脑缺血／复灌沙土鼠脑组织ＣＡ的含量,结果 脑梗塞急性期血浆ＣＡ浓度显著升高,沙土鼠在脑缺血／复灌期间ＣＡ含量明显降低,结论 脑缺血过程中脑内ＣＡ代谢紊乱,递质释放入血增加。     

脑缺血再灌注损伤后大鼠脑内Nestin、 bFGFmRNA的变化研究

目的研究脑缺血再灌注损伤后大鼠脑内神经干细胞增殖相关因子的变化,包括BrdU Nestin、bFGFmRNA。方法采用大鼠脑中动脉缺血再灌注损伤(middle cerebral artery occlusion,MCAO)模型,分假手术组、模型组两组,应用免疫荧光法检测两组3d、5d、7d、14d、21d、30d病灶侧侧脑室区(subventricle zone,SVZ)、海马齿状回(subdentate gyrus zone,SGZ)BrdU Nestin的变化,以及应用RT-PCR方法观察相应时间点两组病灶侧bFGFmRNA的变化。结果假手术组几乎检测不到BrdU Nestin荧光值、bFGFmRNA的表达;模型组病灶侧Br- dU Nestin荧光值、bFGFmRNA表达增高,两组比较有显著差异(P<0.05);各时间点间模型组病灶侧BrdU Nestin荧光值、bFGFmRNA表达均有显著差异(P<0.05);bFGFmRNA的表达值增强早于BrdU Nestin荧光值。结论大鼠脑缺血再灌注损伤可引起病灶侧SVZ、SGZ区神经干细胞反应和增殖;病灶侧bFGFmRNA表达上调可能与神经干细胞增殖分化有关;脑缺血损伤后神经干细胞增殖分化具有时间窗。     

大鼠全脑缺血诱发癫痫模型的建立

建立一个简单,创伤少大鼠癫痫模,以期使该类型癫痫的研究更符合临床病理情况。方法脑部挤压器造成暂时性缺血,复苏后声音诱发癫痫发作,记录其发作情况,分析脑电图变化,并作实验性治疗。     

Pyruvate dehydrogenase activity in the rat cerebral cortex following cerebral ischemia

The effect of cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex following 15 min of bilateral common carotid occlusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate was determined. In cortex from control animals, the rate of [1(-14)C]pyruvate decarboxylation was 9.6 +/- 0.5 nmol CO2/(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was depressed for up to 6 h post ischemia. This decrease in activity was not due to a decrease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 h of recovery. Dichloroacetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p. four times over 2 h, significantly decreased blood glucose levels from 7.4 +/- 0.6 to 5.1 +/- 0.3 mmol/L and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8.3 +/- 0.5 mumol/g by intravenous infusion of glucose, the active portion of PDHC increased to 95 +/- 4%. In contrast, the depressed PDHC activity at 15 min following ischemia was not affected by the DCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

反复性脑缺血丘脑神经元损害的实验研究

目的 :研究反复性脑缺血丘脑神经元的病理损害及其机制。方法 :应用45Ca放射自显影及光镜对比研究大鼠单次性和反复性脑缺血及 NMDA受体拮抗剂 MK- 80 1治疗后丘脑钙积聚和神经元损害的病理改变。结果 :反复缺血组丘脑异常钙积聚与神经元损害明显重于单次缺血组 ;MK- 80 1能显著减轻和改善丘脑钙积聚与组织病理损害。结论 :反复非致死性短暂脑缺血导致丘脑腹侧神经元显著累积性损害 ,兴奋性氨基酸及 Ca2 +可能起着重要作用。     

Seizure activity in the rat hippocampus,perirhinal and prefrontal cortex associated with transient global cerebral ischemia

Summary. Epileptiform EEG activity associated with ischemia can contribute to early damage of hippocampal neurons, and seizure activity may also lead to dysfunction in extrahippocampal regions. In this study, seizure activity associated with the four-vessel occlusion model of cerebral ischemia was monitored using chronically implanted electrodes in the CA1/subicular region, the perirhinal cortex, and the prefrontal cortex of the rat. Background EEG amplitude was reduced in all recording sites during occlusion, but spiking and bursting activity was also observed. Seizure activity occurred in most animals during the first several hours of reperfusion, but was not observed on subsequent days. Epileptiform spikes and bursts were often synchronous between two or three recording sites, and spikes in the CA1 region also often occurred just prior to spikes in other sites. These results demonstrate that the four-vessel occlusion model can lead to patterns of seizure activity in the hippocampus, prefrontal and perirhinal cortices. Correspondence: C. Andrew Chapman, Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, 7141 Sherbrooke Street West, Rm. SP-244, Montreal, Quebec, H4B 1R6 Canada     

GABAB receptors and norepinephrine-stimulated cAMP production in rat brain cortex

The ability of GABAergic compounds to influence cAMP accumulation in rat brain cortex was examined. It was found that GABA_B receptor agonist such as GABA, baclofen, and kojic amine potentiate the cAMP response in cerebral cortex during exposure to norepinephrine. Isoguvacine and THIP, selective GABA_A receptor agonists, did not demonstrate this effect. The response to baclofen was stereoselective, with virtually all activity residing in the (−)isomer. Bicuculline methiodide had no effect on the agonist-induced potentiation and the rank order of potency for GABA_B agonists to potentiate the cAMP response is identical to their rank order of potency in the GABA_B binding assay. These data suggest that GABA_B receptors are capable of influencing the brain cyclic nucleotide system.     

Effect of brain microdialysis on aminergic transmitter levels in repeated cerebral global transient ischemia in rat

The effect of repeated transient global ischemia and microdialysis on changes in aminergic neurotransmitter release was investigated using the rat four-vessel occlusion model of global ischemia. To examine the possible transient or permanent changes in neurotransmitter release, ischemia was induced at varying time points in 5 groups of rats. The first ischemia occurred either 24 h (groups I, II, IV, V) or 96 h (group III) following vertebral artery electro-coagulation and guide probe implantation(s), and the second ischemia was induced either 48 h (groups I, IV, V) or 72 h (group II) following the first ischemia. To assess the consequence of repeated microdialysis on the results, one group of rats (group IV) was not dialysed during the first ischemia and another group (group V) was bilaterally dialysed during the second ischemia. Finally, amphetamine-induced neurotransmitter release was also studied in rats submitted to ischemia and compared with that in normal rats. In each case, dopamine, serotonin and their main metabolites were measured by HPLC with electrochemical detection. Monoamine release was inhibited during the second episode of transient ischemia; this non-release was linked to the repeated microdialysis and not to the repeated ischemia. Although the results of chronic studies using brain microdialysis have been widely recognized as valid, the findings presented here indicate that combined with ischemia, probe reinsertion modifies the level of neurotransmitter release.     

Dynamic expression of cerebral cortex and hippocampal glutamate transporters in a rat model of chest compression-induced global cerebral ischemia

The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis. Expression of glutamate-aspartate transporter remained unchanged at 6 hours-7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.     

Neuronal damage following non-lethal but repeated cerebral ischemia in the gerbil

Summary Brief, non-lethal transient forebrain ischemia in the gerbil can injure selectively vulnerable neurons when such ischemia is induced repeatedly. The influence of the number and interval of the ischemic insults on neuronal damage, as well as the time course of damage, following repeated 2-min forebrain ischemia were examined. A single 2-min forebrain ischemia were examined. A single 2-min ischemic insult caused no morphological neuronal damage. A moderate number of hippocampal CA1 neurons were destroyed following two ischemic insults with a 1-h interval, and destruction of almost all CA1 neurons resulted from three or five insults at 1-h intervals. Three and five insults also resulted in moderate to severe damage to the striatum and thalamus, depending on the number of episodes. Although three ischemic insults at 1-h intervals caused severe neuronal damage, this number of insults at 5-min and 4-h intervals caused destruction of relatively few neurons, and non neurons were destroyed at 12-h intervals. Following three ischemic insults at 1-h intervals, damage to the striatum, neocortex, hippocampal CA4 subfield and thalamus was observed at 6–24 h of survival, whereas damage to the hippocampal CA1 subfield appeared at 2–4 days. The results indicate that even a brief non-lethal ischemic insult can produce severe neuronal damage in selectively vulnerable regions when it is induced repeatedly at a certain interval. The severity of neuronal damage was dependent on the number and interval of ischemic episodes.