Clinical analysis of neurotoxity in water intoxication and experimental elucidation of its mechanism

为了建立抗精神病药物水中毒大鼠模型，我们尝试建立抗精神病药物脑室连续输注系统。首先，饲喂160 ~ 170g雄性Wistar大鼠21 d，记录基本行为学数据。在戊巴比妥麻醉下，在SRO中放置不锈钢导管。然后用渗透泵通过小管连续注射生理盐水。3周后，经组织病理学观察证实。为此，研制了连续注射系统，并将其应用于水中毒检测。采用识别caspase - 3片段的抗caspase - 3抗体和Tunnel染色，采用免疫组织学方法检测神经元凋亡情况。这些观察结果表明，在正常大鼠脑中，一些神经元也处于凋亡状态。最后，我们开发了一种针对DDB1的抗体，该抗体在DNA损伤时易位到细胞核，抗体的观察表明，凋亡的神经元没有显示DNA修复。

In order to develop the model rats of water intoxication induced by anti-psychotic drug administration, we tried to establish the system of the continuous infusion into the ventricles. First, male Wistar rat of 160-170g were fed for 21 days, and the basic behavioral data were taken. Next, stainless guide-canule was set in SRO under the anesthesia of pentobarbital. Then, saline was continuously injected by osmotic pump through the canule. After 3 weeks, the injection was confirmed by histopathological observations. Thus, the continuous injection system was developed and applied to the examination of water intoxication.And apoptosis of neurons was examined by immunohistological method using anti-caspase 3 antibody that recoginizes the fragmented caspase 3, and by Tunnel staining. These observations showed that some neurons were fallen in apoptotic state even in normal rat brain.Finally, we developed an antibody agaisnt DDB1 which translocates to nucleus at DNA damage, and the observations with the antibody indicated that the apoptotic neurons did not show the DNA repair.