Karst H, de Kloet E R, Joëls M
Department of Exp. Zoology, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
Eur J Neurosci. 1999 Mar;11(3):889-98. doi: 10.1046/j.1460-9568.1999.00495.x.
We tested the effect of episodic (approximately 10 days) corticosterone treatment on: (i) behavioural symptoms during kindling epileptogenesis; and (ii) electrical activity in the CA1 hippocampal area during epileptogenesis, and later on, in the fully kindled state. Male rats received a corticosterone-releasing pellet (100 mg/day) shortly before kindling was started, resulting in elevated hormone levels during the early and middle stages of epileptogenesis. The appearance of moderate behavioural signs of epilepsy and severe tonic-clonic seizures was significantly accelerated in corticosterone-treated animals compared to placebo controls. During epileptogenesis, corticosterone treatment did not affect the amplitude and paired-pulse characteristics of in vivo-recorded CA1 field responses, or the duration of the afterdischarge following tetanic stimulation of the Schaffer collaterals. However, other properties of CA1 cells studied in vitro, in the fully kindled state, were altered by the earlier episodic corticosterone treatment. Thus, in kindled rats, the amplitude of the population spike in the CA1 area was significantly enhanced after prior exposure to high corticosterone levels. Prior episodic steroid treatment resulted furthermore in a significantly increased amplitude of voltage-gated Ca currents, in kindled rats. At that time, corticosterone levels of animals which had received a corticosterone-releasing pellet earlier were no longer elevated compared to the placebo controls; the corticosteroid-treated rats did also not differ from the controls with respect to the mRNA expression levels for the two corticosteroid receptor subtypes in the hippocampus. The data suggest that exposure of animals to a period of stressful experiences during a critical phase in epileptogenesis could impose lasting deleterious effects on the course of epilepsy, even when CORT levels have been normalized again.
我们测试了阶段性（约10天）皮质酮治疗对以下方面的影响：（i）点燃癫痫发作过程中的行为症状；（ii）癫痫发作过程中以及后来在完全点燃状态下海马CA1区的电活动。雄性大鼠在点燃开始前不久接受了皮质酮释放丸剂（100毫克/天），导致癫痫发作早期和中期激素水平升高。与安慰剂对照组相比，接受皮质酮治疗的动物出现中度癫痫行为体征和严重强直阵挛性发作的时间明显加快。在癫痫发作过程中，皮质酮治疗不影响体内记录的CA1场反应的幅度和双脉冲特征，也不影响对Schaffer侧支进行强直刺激后的放电持续时间。然而，在完全点燃状态下体外研究的CA1细胞的其他特性因早期的阶段性皮质酮治疗而发生了改变。因此，在点燃的大鼠中，先前暴露于高皮质酮水平后，CA1区群体峰电位的幅度显著增强。先前的阶段性类固醇治疗还导致点燃大鼠电压门控钙电流的幅度显著增加。此时，与安慰剂对照组相比，早期接受皮质酮释放丸剂的动物的皮质酮水平不再升高；在海马中两种皮质类固醇受体亚型的mRNA表达水平方面，接受皮质类固醇治疗的大鼠与对照组也没有差异。数据表明，在癫痫发作的关键阶段使动物经历一段应激经历，即使皮质酮水平已恢复正常，也可能对癫痫病程产生持久的有害影响。
