STRUCTURE & FUNCTION OF MITOCHONDRIA

短暂性脑缺血使神经元去极化，增加 胞外谷氨酸和胞内钙的变化 脑缺血后阶段的突触效能。的影响 短暂性脑缺血相当于强直性脑缺血 受损区域内的电刺激。我们呈现的是 短暂性脑缺血引起显著的生化和 突触后密度(PSD)的超微结构变化。瞬变 双侧颈总动脉结扎诱导大鼠脑缺血 动脉灌注15min，再灌流4h。在这些 动物，在分离的皮质部分测量的PSD的产量 比对照组增加了2.4910.23倍。这种蛋白质 如图所示，重建了再灌流的PSD的组成 考马斯亮蓝染色和免疫印迹法检测。最引人注目的 变化是再灌流的PSD中蛋白激酶的积聚。 包括p38-激酶、JNK1、gp145trkB、CaM-激酶II、蛋白激酶C 和酪氨酸激酶。PSD蛋白的磷酸化状态 再灌流后也明显升高。这些生物化学 这些变化与超微结构的改变一致 在为电子显微镜准备的PSD中观察到。隔离的PSD 缺血后的动物比 控制。PSD结构在组织中也发生了戏剧性的变化 再灌流动物大脑皮层切片染色 磷钨酸选择性地对PSD进行染色。很明显，PSD 比对照组更厚，形状更不规则，更不紧凑。 我们得出结论，信号转导分子在PSD和PSD中的对接 PSD蛋白的磷酸化是导致变化的重要因素 在刺激后的突触效率。这本书出版了 见胡等，《神经科学杂志》，1998年，18：625-633。在过去一年中，我们 对CA1中的PSD变化进行了更详细的量化分析 缺血区海马齿状回。使用厚截面和 IVEM，我们进行了突触的断层重建 脑缺血大鼠和正常大鼠不同时间点的海马区 再灌流。这些重建清楚地表明，大脑中的突触 缺血脑组织中CA1区的结构比 控制大脑。3D图像表明，CA1中的突触是 在明显的细胞死亡之前经历退化的变化。这 在神经科学学会年会上发表了这项工作， 一份手稿已经提交给了《神经科学杂志》。

Transient cerebral ischemia depolarizes neurons, increases extracellular glutamate and intracellular calcium, and changes synaptic efficacy in the post-ischemic phase. The effects of transient ischemia are equivalent to those produced by strong electrical stimulation within the compromised area. We present evidence that transient ischemia induces marked biochemical and ultrastructural changes in postsynaptic densities (PSDs). Transient ischemia was induced in rats by bilateral ligation of the carotid arteries for 15 min followed by 4 hr of reperfusion. In these animals, the yield of PSDs as measured in isolated fractions of cortex was increased by a factor of 2.4910.23 over controls. The protein composition of the reperfused PSDs was reconstituted as demonstrated by Coomasie blue staining and Western Blots. The most remarkable changes were an accumulation of protein kinases in reperfused PSDs including p38-kinase, JNK1, gp145trkB, CaM-kinase II, protein kinase C and tyros ine kinases. The phosphorylation states of PSD proteins were also markedly increased following reperfusion. These biochemical alterations were consistent with ultrastructural modifications observed in PSDs prepared for electron microscopy. PSDs isolated from post-ischemic animals were longer and thicker than those from controls. PSD structure was also dramatically altered in tissue sections from the cortex of reperfused animals stained with phosphotungstic acid to selectively stain PSDs. PSDs were noticeably thicker, more irregular in shape and less compact than in controls. We conclude that docking of signal transduction molecules in PSDs and phosphorylation of PSD proteins are important contributors to changes in synaptic efficacy following stimulation. This work was published in Hu et al., J. Neurosci., 18: 625-633, 1998. In the past year, we performed a more detailed quantitative analysis of PSD changes in CA1 and dentate gyrus in ischemic hippocampus. Using thick sections and IVEM, we performed tomographic reconstructions of synapses in the hippocampus of ischemic and control rats at different time points of reperfusion. These reconstructions clearly showed that synapses in area CA1 were more loosely configured in the ischemic brain than in control brains. The 3D images suggest that synapses in CA1 are undergoing degenerative changes prior to obvious cell death. This work was presented at the Annual Society for Neuroscience meeting and a manuscript has been submitted to the Journal of Neuroscience.