de Feo M R, Mecarelli O, Ricci G F
Department of Neurological Science, La Sapienza University, Rome, Italy.
Pharmacol Res. 1995 Feb;31(2):109-14. doi: 10.1016/1043-6618(95)80055-7.
The administration of the alkylating neurotoxin methylazoxymethanol acetate (MAM) to pregnant rats on day 15 of gestation induces, in the offspring, a marked micrencephaly, characterized by an impaired formation of interneurons at cortical, hippocampal and striatal levels. Since in man developmental CNS malformations are often associated with severe epileptogenic encephalopathies with seizures appearing in the first months or years of life, we have studied the development of kainic-acid- and bicuculline-induced seizures in 15- and 30-day-old rats, prenatally exposed to MAM. Compared to controls, a higher susceptibility to seizures has been found in micrencephalic rats aged 15 days, while no significant differences have been observed in those aged 30 days. It is hypothesized that the cerebral global anatomical dysgenesis caused by MAM underlies the higher seizure susceptibility shown by animals during the first periods of life. Successively, the processes of adjustment occurring between the cerebral regions affected by the neurotoxic action of MAM and the afferent and efferent pathways spared by the substance may re-establish adequate interneuronal relationships and, therefore, a normal convulsive susceptibility.
在妊娠第15天给怀孕大鼠注射烷基化神经毒素乙酸甲基偶氮甲醇（MAM），会使子代出现明显的小脑畸形，其特征是皮质、海马和纹状体水平的中间神经元形成受损。由于在人类中，中枢神经系统发育畸形常与严重的致癫痫性脑病相关，癫痫发作出现在生命的最初几个月或几年，我们研究了产前暴露于MAM的15日龄和30日龄大鼠中，由海藻酸和荷包牡丹碱诱导的癫痫发作的发展情况。与对照组相比，15日龄的小脑畸形大鼠对癫痫发作的易感性更高，而30日龄的大鼠未观察到显著差异。据推测，MAM引起的大脑整体解剖发育异常是动物在生命最初阶段表现出较高癫痫易感性的基础。随后，受MAM神经毒性作用影响的脑区与该物质未损伤的传入和传出通路之间发生的调节过程，可能会重新建立适当的中间神经元关系，从而恢复正常的惊厥易感性。
