癫癎的生理性与病理性惊厥发作阈值的探讨

Experimental research on physiological and pathological electric convulsion thresholds in rats

目的:探讨大鼠惊厥发作阈值由生理性向病理性过渡时的脑电变化,以及病理性惊厥发作阈值(癫癎发作阈值)与生理性惊厥发作阈值的区别。方法:以鼠模型作为观察对象,直接电刺激大鼠皮层测定惊厥阈值。连续11周给予大鼠皮层电刺激,每日两次,动态观察大鼠的惊厥发作时的刺激阈值、皮层脑电活动以及海马的病理改变情况。结果:实验最初大鼠皮层惊厥发作阈值高,局限性发作的惊厥阈值(TLS)为1 145±403.37μA,全面性发作的惊厥阈值(TGS)为1 277±443.15μA,延续性发作的惊厥阈值(TPS)为1 449±472.45μA,但个体差异大,在电刺激开始的4周内,各组大鼠的惊厥发作阈值迅速下降。随着刺激时点延长其下降趋势逐渐平稳,至电刺激第10周逐渐稳定在一个较低的水平且不再变化,此时大鼠间个体差异亦减小(TLS 430±34μA),(TGS 480±46μA),TPS 605±70μA),与刺激初期相比差异有显著意义(P<0.01)。强电流刺激组在第三周,弱电流刺激组在第八周分别出现了自发后放电现象,同期的海马组织学观察亦发现神经元缺失和损伤改变,对照组未见异常。结论:脑内存在的惊厥发作阈值应分为生理性和病理性两个阶段。而病理性惊厥发作阈值(癫癎发作阈值)是由病理因素造成的一种慢性脑损害结果,病理性的刺激因素与刺激强度对这一形成过程成正相关作用。

Objectives: To investigate changes that occur in the brain when the physiological convulsive thresholds become pathological and to determine what differences occur in pathological and physiological convulsive thresholds during the development of epilepsy. Methods: The determination of the thresholds for convulsions was made by direct cortical stimulation to brains of rates. The convulsive thresholds were measured while electroencephalograms were recorded and histopathological changes were subsequently examined in the hippocampus. Results:At the beginning of the experiment, convulsive thresholds were all above 1100μA although there were significant individual variations in rats of the same group. But those thresholds quickly declined during the first 4 weeks of repetitive electrical stimulation. The convulsive thresholds approached a constant level,thresholds of localized seizure(TLS)430±34μA, thresholds of generalized seizure (TGS)480±46μA, threshold of prolonged seizure (TPS)605±70μA in at the 10th week. There were no significant changes in thresholds when stimulation lasted longer, the convulsive thresholds and the variations in rats of the same group were significantly lower than that at the beginning of the trial(P<0. 01). An interictal discharge of the heavy current group was also recorded in the 3rd week in and that of the weak current group in the 8th week respectively which were concomitant with the neuronal damage and loss in the hippocampus. No abnormality was observed in the control group. Conclusions: These findings indicate that the convulsion thresholds in the brain should be divided into two stages: the physiological convulsive thresholds and the pathological convulsive thresholds (epileptic threshold). Epileptic threshold is created by pathological acquired factors causedby brain damage. The intensity of these pathological acquired factors are correlated with the formation of the pathological convulsive threshold.