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梭曼诱导的癫痫持续状态后自发反复性癫痫发作于 Sprague-Dawley 大鼠。

Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats.

机构信息

Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.

出版信息

Epilepsia. 2010 Aug;51(8):1503-10. doi: 10.1111/j.1528-1167.2009.02478.x. Epub 2010 Jan 7.

Abstract

PURPOSE

Exposure to toxic levels of organophosphorus (OP) nerve agents can lead to seizures, respiratory failure, and, if untreated, death. The cholinesterase inhibitor soman belongs to the class of OP nerve agents and can cause status epilepticus (SE) and brain damage due to neuroexcitotoxicity. In the present study, electroencephalographic seizures are characterized through telemetry implants in rats exposed to soman, followed by treatment with therapeutics similar to those administered after nerve agent exposure.

METHODS

Cortical electroencephalography (EEG), motor activity and body temperature were recorded continuously for 2 days preexposure and 15 days postexposure to verify the occurrence of spontaneous recurrent seizures (SRS) after soman exposure.

RESULTS

Behavioral seizures were monitored and the latency to SE was 7.8 ± 4.0 min after exposure. Among the rats that showed SE, approximately 90% had prolonged seizures within the initial 3 days after soman exposure. Five percent of the rats developed stage 1 seizures, 16% stage 2, 23% stage 3, 18% stage 4, and 38% stage 5. Seventy-nine percent of the rats presented SE and epileptiform-like discharges several days after SE, and 28.9% of those with SE experienced electrographic SRS. The latency to the appearance of SRS ranged from 5-10 days. Fiber degeneration evaluated through silver staining revealed damage in cortical and subcortical areas directly correlated with SE.

DISCUSSION

The presence of SRS after seizures induced by soman highlights the importance of quantifying SRS in studies where the objective is to find new therapeutics against soman-induced seizures.

摘要

目的

接触有毒水平的有机磷(OP)神经毒剂可导致癫痫发作、呼吸衰竭,如果不治疗,还会导致死亡。拟除虫菊酯 soman 属于 OP 神经毒剂类,可引起癫痫持续状态(SE)和神经毒性引起的脑损伤。在本研究中,通过对 soman 暴露大鼠的遥测植入物来对脑电图癫痫发作进行特征描述,然后用类似于神经毒剂暴露后给予的治疗方法进行治疗。

方法

在暴露前 2 天和暴露后 15 天连续记录皮质脑电图(EEG)、运动活动和体温,以验证 soman 暴露后是否发生自发性复发性癫痫发作(SRS)。

结果

监测到行为性癫痫发作,SE 的潜伏期为暴露后 7.8±4.0 分钟。在出现 SE 的大鼠中,约 90%在 soman 暴露后的最初 3 天内出现长时间癫痫发作。5%的大鼠出现 1 期发作,16%出现 2 期发作,23%出现 3 期发作,18%出现 4 期发作,38%出现 5 期发作。79%的大鼠在 SE 后几天出现 SE 和癫痫样放电,并且有 SE 的大鼠中有 28.9%出现电描记 SRS。SRS 出现的潜伏期范围为 5-10 天。通过银染色评估纤维变性显示,与 SE 直接相关的皮质和皮质下区域存在损伤。

讨论

soman 诱导的癫痫发作后出现 SRS,突出了在旨在寻找针对 soman 诱导的癫痫发作的新治疗方法的研究中定量 SRS 的重要性。

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