Mechanism of Ischemic Neuronal Death : Neuron, Glial interaction

本实验旨在研究(1)缺血后神经胶质细胞的活化，(2)肝素结合生长相关分子的表达，以期获得预防缺血性痴呆的线索。(1)应激激活分子在胶质细胞中的诱导小胶质细胞在缺血后被激活，呈现出各种免疫反应分子。星形胶质细胞呈现应激蛋白，如HSP27。缺血区中性粒细胞表达细胞粘附分子。这些数据表明，能够干预免疫过程的化学物质有望用于缺血性脑损伤的治疗。(2)神经营养物质与缺血我们主要研究肝素结合生长相关分子（HB-GAM），因为HB-GAM对各种类型的神经元都有营养作用。我们观察到HB-GAM在正常CA1锥体神经元中表达。CA1神经元缺血死亡后，CA1亚区HB-GAM表达明显增强，反应性星形胶质细胞是HB-GAM的主要来源。缺血后HB-GAM受体Syndecan-3水平也发生改变。这些结果提示HB-GAM可能在神经元存活和突触重排中起重要作用。盐酸联苯醚（BF）是胆碱能系统的调节剂，可增加毒蕈碱类胆碱能受体的密度。缺血后用BF治疗100天的动物海马胆碱酯酶活性增加。因此，调节胆碱能系统可能有利于缺血性脑功能障碍的治疗。

The present was designed to study (1) glial cell activation, and (2) heparin-binding growth-associated molecule exression after ischemia in order to obtain a clue to prevent ischemia-induced dementia.(1) Induction of stress-activated molecules in the glial cellsMicroglial cells were activated after ischemia and presented various immuno-reactive molecules. Astroglial cells presented stress proteins, such as HSP27. Neutrophils in ischemic areas expressed cell adhesion molecules. These data suggest that chemicals that can intervene immunological processes could be promissing for the treatment of ischemic brain injury.(2) Neurotrophic substances and ischemiaWe focused upon heparin-binding growth-associated molecules (HB-GAM), as HB-GAM shows trophic effects on various types of neurons. We observed that HB-GAM is expressesd in normal CA1 pyramidal neurons. After ischemic death of CA1 neuron, HB-GAM expression in the CA1 subfield was markedly enhanced and reactive astrocytes were the major source of HB-GAM.The level of Syndecan-3, the receptor for HB-GAM,was also altered after ischemia. These results suggest that HB-GAM may play an important role for neuronal survival and synaptic rearrangement.Bifemelane hydrochloride (BF) is a modulator of cholinergic systems and increases muscarinic cholinergic receptor density. Animals treated with BF for one-hundred days after ischemia showed increased cholinesterase activity in the hippocampus. Thus, modulation of cholinergic system could be beneficial for the treatment of post-ischemic brain dysfunction.