Weber M L, Taylor C P
Department of Neuroscience Pharmacology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105.
Brain Res. 1994 Nov 21;664(1-2):167-77. doi: 10.1016/0006-8993(94)91967-4.
In vitro ischemia (IVI) was simulated with rat hippocampal slices in medium lacking D-glucose, equilibrated with 95% nitrogen, 5% carbon dioxide. Within 5-8 min, synaptic potentials disappeared and a DC negative shift (5-15 mV) occurred. Prolonged application of 95% oxygen and D-glucose 12 min later did not allow synaptic potentials to recover. Slices pretreated with sodium channel blocking drugs allowed synaptic potentials to recover after IVI. Tetrodotoxin (TTX, 100-600 nM), the anticonvulsant phenytoin (5.0 to 100 microM) and the local anesthetic lidocaine (2.0 to 200 microM) each delayed or prevented negative DC shifts from IVI. Histological examination showed that drug treatments also prevented CA1 pyramidal cell damage from IVI. Neuroprotection occurred without blocking synaptic potentials or presynaptic fiber volleys, suggesting relevance for treatment of brain ischemia.
利用大鼠海马切片在缺乏D-葡萄糖的培养基中模拟体外缺血（IVI），该培养基用95%氮气和5%二氧化碳平衡。在5-8分钟内，突触电位消失，并出现直流负向偏移（5-15毫伏）。12分钟后长时间施加95%氧气和D-葡萄糖并不能使突触电位恢复。用钠通道阻断药物预处理的切片在IVI后可使突触电位恢复。河豚毒素（TTX，100-600纳摩尔）、抗惊厥药苯妥英（5.0至100微摩尔）和局部麻醉药利多卡因（2.0至200微摩尔）均可延迟或防止IVI引起的直流负向偏移。组织学检查表明，药物治疗还可防止IVI引起的CA1锥体细胞损伤。神经保护作用的发生并未阻断突触电位或突触前纤维放电，提示其与脑缺血治疗相关。
