Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats
Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats
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DOI：
10.1111/j.1528-1167.2009.02478.x
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发表时间：
2010-08-01
期刊：
影响因子：
5.6
通讯作者：
Yourick, Debra L.
中科院分区：
文献类型：
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作者：
Furtado, Marcio de Araujo;Lumley, Lucille A.;Yourick, Debra L.
目的：暴露于毒性水平的有机磷(OP)神经毒剂可导致癫痫发作、呼吸衰竭，如果不治疗，还会死亡。胆碱酯酶抑制剂梭曼属于OP类神经毒剂，可由于神经兴奋毒性而导致癫痫持续状态(SE)和脑损伤。在本研究中，通过植入遥测的方法，在大鼠脑内植入梭曼，然后进行类似于神经毒剂暴露后的治疗。方法：连续记录暴露前2d和暴露后15d的皮层脑电(EEG)、运动活动和体温，以验证暴露后自发性反复发作(SRS)的发生。结果：监测到行为发作，暴露后SE潜伏期为7.8+/-4.0min。在表现为SE的大鼠中，大约90%的大鼠在接触梭曼后的最初3天内有较长时间的癫痫发作。5%的大鼠出现1期癫痫发作，16%的2期癫痫发作，23%的3期癫痫发作，18%的4期癫痫发作，38%的5期癫痫发作。79%的癫痫大鼠在SE后几天出现癫痫样放电，28.9%的SE大鼠出现脑电SRS。出现SRS的潜伏期为5~10天。通过银染评估纤维变性，发现皮质和皮质下区域的损害与SE直接相关。讨论：梭曼诱发癫痫后SRS的存在突显了量化SRS在旨在寻找新的治疗方法对抗梭曼诱导癫痫的研究中的重要性。
P>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.