Choi In-Sun, Cho Jin-Hwa, Lee Maan-Gee, Choi Byung-Ju
Department of Dental Pharmacology, College of Dentistry, Kyungpook National University, Daegu 702-412, Korea.
Biol Pharm Bull. 2005 Aug;28(8):1408-13. doi: 10.1248/bpb.28.1408.
Several rodent models of cortical malformation are available for the study of cellular mechanisms associated with early-onset epilepsy, but few are associated with spontaneous seizures. We examined the effect of pilocarpine on the spontaneous seizure development and excitability of the CA1 pyramidal cells of rats after prenatal treatment with methylazoxymethanol (MAM). Pilocarpine induced status epilepticus (SE) onset latency was greater for normal rats than for MAM-treated rats. After several days of normal behavior following pilocarpine treatment, the duration of spontaneous seizures were greater in MAM-pilocarpine rats than in normal-pilocarpine rats. Compared with the normal rats, electrical stimulation of afferent fibers resulted in more robust population responses in the CA1 region in all groups. At interstimulus intervals of 30 and 70 ms, the MAM-pilocarpine rats displayed a decrease in paired pulse inhibition versus the conventional MAM rats. A loss of somatostatin- and parvalbumin-immunoreactive neurons was apparent in the normal-pilocarpine rats, MAM-pilocarpine rats, and conventional MAM rats. These results indicate that pilocarpine induces spontaneous seizures and hyperexcitability in MAM-pilocarpine rats.
有几种皮质发育畸形的啮齿动物模型可用于研究与早发性癫痫相关的细胞机制，但很少与自发性癫痫发作相关。我们研究了毛果芸香碱对产前用甲基氧化偶氮甲醇（MAM）处理的大鼠自发癫痫发作发展及CA1锥体细胞兴奋性的影响。毛果芸香碱诱导癫痫持续状态（SE）的发作潜伏期，正常大鼠比MAM处理的大鼠更长。在用毛果芸香碱处理后经过几天的正常行为，MAM-毛果芸香碱大鼠的自发性癫痫发作持续时间比正常-毛果芸香碱大鼠更长。与正常大鼠相比，对传入纤维的电刺激在所有组的CA1区域均导致更强有力的群体反应。在刺激间隔为30和70毫秒时，与传统MAM大鼠相比，MAM-毛果芸香碱大鼠的双脉冲抑制作用减弱。在正常-毛果芸香碱大鼠、MAM-毛果芸香碱大鼠和传统MAM大鼠中，生长抑素和小白蛋白免疫反应性神经元明显缺失。这些结果表明，毛果芸香碱在MAM-毛果芸香碱大鼠中诱导自发性癫痫发作和兴奋性过高。
