Stringer J L, Erden F
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.
Exp Brain Res. 1995;105(3):391-401. doi: 10.1007/BF00233039.
Using a reverberatory epilepiform discharge of hippocampal-parahippocampal circuits termed "maximal dentate activation", this study investigated whether the local release of nitric oxide within these circuits functions as an antiepileptic agent. Two nitric oxide synthase inhibitors (L-nitro-arginine methyl ester and 7-nitro-indazole) and a guanylate cyclase inhibitor (methylene blue) were tested, and none had a significant effect on the time to onset or duration of maximal dentate activation. A membrane-permeable analogue of cyclic guanosine monophosphate (cGMP), 8-bromo-cGMP, caused an increase in the time to onset and a decrease in the duration of maximal dentate activation. The number of neurons expressing NADPH diaphorase activity (a marker for nitric oxide synthase) was also examined after repeated elicitation of maximal dentate activation. After 18 seizures there was a significant, but transient, decrease in the number of hilar/subgranular neurons that were NADPH diaphorase-positive. The decrease was only seen at 1 h after the last seizure. There was no induction of NADPH diaphorase activity. These results are not consistent with the hypothesis that, in hippocampal-parahippocampal circuits in vivo, nitric oxide is released in response to neuronal activity and then acts to terminate the neuronal activity.
本研究运用被称为“最大齿状回激活”的海马-海马旁回回路的回响样癫痫样放电，探究了这些回路中一氧化氮的局部释放是否起到抗癫痫剂的作用。测试了两种一氧化氮合酶抑制剂（L-硝基-精氨酸甲酯和7-硝基吲唑）以及一种鸟苷酸环化酶抑制剂（亚甲蓝），结果发现它们对最大齿状回激活的起始时间或持续时间均无显著影响。一种可透过细胞膜的环磷酸鸟苷（cGMP）类似物8-溴-cGMP，使最大齿状回激活的起始时间延长，持续时间缩短。在反复引发最大齿状回激活后，还检测了表达NADPH黄递酶活性（一氧化氮合酶的标志物）的神经元数量。在18次发作后，海马门/颗粒下区NADPH黄递酶阳性神经元的数量出现显著但短暂的减少。这种减少仅在最后一次发作后1小时出现。未观察到NADPH黄递酶活性的诱导。这些结果与以下假设不一致：在体内海马-海马旁回回路中，一氧化氮会响应神经元活动而释放，然后起到终止神经元活动的作用。
