New development of basic study on protection of ischemic brain edema and neuronal dysfunction using brain slice model

(1)采用膜电位成像技术对沙鼠前脑缺血2 min预处理后的脑切片进行缺血预处理诱导的缺血耐受研究。预处理动物海马切片的兴奋增殖部分保留，而未处理动物海马切片的兴奋增殖在短暂缺血5min后1天消失。预处理动物的锥体神经元在缺血损伤后2个月仍能保存。结果提示，缺血预处理可诱导缺血耐受，减轻缺血功能障碍程度。(2)观察短暂缺氧-葡萄糖剥夺脑切片的兴奋传播。海马CA1和皮质II-III层的诱发兴奋传播在缺氧葡萄糖暴露期间减少，但在缺氧葡萄糖暴露5分钟后3-5小时部分恢复。暴露后1天（20 ~ 22小时），海马片的兴奋传播基本消失，皮质片的兴奋传播部分保留。另一方面，在氯胺酮和硫胺醛存在的情况下缺氧葡萄糖暴露的海马和皮质切片中的兴奋传播在暴露后1天仍保存良好。结果表明，短暂缺氧对海马神经元功能的损害比皮质神经元功能的损害更严重。一些静脉麻醉药，如氯胺酮和硫胺酮，可以保护神经元免受缺血时氧-葡萄糖的消耗。(3)利用高速光学成像技术观察三叉神经尾侧亚核（Vc）神经元兴奋的传播过程。高频刺激在边缘层、明胶质和大细胞层引起长时间的膜去极化。MK-801或L-703.606抑制了这种兴奋传递，提示NMDA-和nk_1受体参与了Vc的伤害性传入传递。少

(1) Ischemic tolerance induced by ischemic preconditioning was investigated by applying a membrane potential imaging technique to brain slices of gerbils, which were pretreated with 2-min forebrain ischemia. Excitation propagation in hippocampal slices of preconditioned animals was partially preserved, while that of untreated animals disappeared 1 day after 5-min transient ischemia. Pyramidal neurons of preconditioned animals were also preserved 2 months after the ischemic insult. The results suggest that ischemic preconditioning induced ischemic tolerance to reduce the extent of ischemic functional disturbance.(2) Excitation propagation in brain slices, which were transiently exposed to oxygen-glucose deprivation, was examined. Evoked excitation propagation in the hippocampal CA1 and cortical layer II-III were diminished during exposure to oxygen-glucose deprivation, but partially recovered 3-5 hr after 5-min exposure to oxygen-glucose deprivation. The excitation propagation almost di … More sappeared in hippocampal slices 1 day (20-22 hr) after the exposure, while that in cortical slices was partially preserved. On the other hand, excitation propagation in both hippocampal and cortical slices, which were exposed oxygen-glucose deprivation in the presence of ketamine and thiamylal, well preserved even 1 day after the exposure. The results indicate that neuronal function in hippocampal slices more severely damaged than that in cortical slices by transient exposure to oxygen-glucose deprivation. Some intravenous anesthetics, e.g. ketamine and thiamylal, may protect neurons from oxygen-glucose depletion during ischemia.(3) Propagation of neuronal excitation in the trigeminal subnucleus caudalis (Vc) was visualized using a high-speed optical imaging technique applied to medulla slice preparations. High frequency stimulation induced long-lasting membrane depolarization in the marginal layer, substantia gelatinosa and magnocellular layer. This excitation propagation was suppressed by MK-801 or L-703.606, suggesting that NMDA- and NK_1-receptors are involved in the nociceptive afferent transmission in Vc. Less