Impact of corticosterone treatment on spontaneous seizure frequency and epileptiform activity in mice with chronic epilepsy.

Impact of corticosterone treatment on spontaneous seizure frequency and epileptiform activity in mice with chronic epilepsy.
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DOI:
10.1371/journal.pone.0046044
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Danzer SC
Danzer SC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Castro OW;Santos VR;Pun RY;McKlveen JM;Batie M;Holland KD;Gardner M;Garcia-Cairasco N;Herman JP;Danzer SC

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压力是癫痫患者癫痫发作最常见的诱发因素。尽管有令人信服的轶事证据表明应激诱导癫痫发作,但这种现象的动物模型很少,可能的机制也不清楚。在这里,我们测试的假设,增加水平的应激相关激素皮质酮(CORT)将增加癫痫样活动和自发性癫痫发作的频率在小鼠呈现癫痫后匹罗卡品诱导的癫痫持续状态。我们监测视频脑电图活动在毛果芸香碱治疗的小鼠24/7的一段时间为4个星期或更长的时间,在此期间,动物连续治疗与CORT或车辆。CORT在治疗的前24小时内增加癫痫样事件的频率和持续时间,并且这种作用在CORT注射终止后持续长达两周。有趣的是,溶媒注射产生了CORT水平的短暂峰值-可能是由于注射应激-以及癫痫样活动的适度但显著的增加。CORT或溶剂处理均未显著改变癫痫发作频率;尽管一小部分动物确实出现反应。两者合计,我们的研究结果表明,治疗癫痫动物与外源性CORT旨在模拟慢性应激可诱导持续增加发作间期癫痫样活动。
Stress is the most commonly reported precipitating factor for seizures in patients with epilepsy. Despite compelling anecdotal evidence for stress-induced seizures, animal models of the phenomena are sparse and possible mechanisms are unclear. Here, we tested the hypothesis that increased levels of the stress-associated hormone corticosterone (CORT) would increase epileptiform activity and spontaneous seizure frequency in mice rendered epileptic following pilocarpine-induced status epilepticus. We monitored video-EEG activity in pilocarpine-treated mice 24/7 for a period of four or more weeks, during which animals were serially treated with CORT or vehicle. CORT increased the frequency and duration of epileptiform events within the first 24 hours of treatment, and this effect persisted for up to two weeks following termination of CORT injections. Interestingly, vehicle injection produced a transient spike in CORT levels – presumably due to the stress of injection – and a modest but significant increase in epileptiform activity. Neither CORT nor vehicle treatment significantly altered seizure frequency; although a small subset of animals did appear responsive. Taken together, our findings indicate that treatment of epileptic animals with exogenous CORT designed to mimic chronic stress can induce a persistent increase in interictal epileptiform activity.
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