恒河猴慢性颞叶癫痫模型的构建与评价

发布时间：2018-03-14 13:17

本文选题：恒河猴　切入点：动物模型　出处：《南方医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究背景:癫痫是一种常见的慢性神经系统疾病,应用癫痫动物模型研究癫痫致痫机制及猝发机理,目前已取得了大量的研究成果。然而当前研究以啮齿类动物模型为主,其与人类存在种属差异性,难以复制人类癫痫神经网络及相关症状学表现。故有必要构建一个灵长类癫痫动物模型为癫痫网络相关研究提供基础。本研究拟利用脑立体定向技术在杏仁核植入微导管及皮下储液囊,经储液囊重复注射致痫剂海人酸(Kainic Acid,KA),以此方法构建恒河猴慢性颞叶癫痫模型。目的:探索建立非人灵长类慢性颞叶癫痫动物模型的方法,并对造模效果进行评价,使其能够用于致痫网络形成等相关研究。方法:首先利用脑立体定向技术在右侧杏仁核靶向植入微导管,并连接皮下储液囊,待动物康复后,在视频脑电图监测下经储液囊注射KA,两周后再行视频脑电图监测。若脑电记录既无发作间期癫痫样放电(Interictal Epileptiform Discharges,IEDs)也没有捕捉到发作放电,则再次注射KA,否则仅予视频脑电图记录。选取其中2只动物埋藏双侧硬膜下电极,定期进行颅内电极脑电监测。结果:在杏仁核注射KA期间,头皮脑电记录没有明显放电活动,动物无明显抽搐表现。经过多次KA注射后,在慢性期阶段,动物记录到IEDs,并捕捉到完整的发作期放电,发作期动物表现为愣神、茫然四顾、偶有口面部自动症(咀嚼、舔舌、吞咽动作等),肢体无明显抽搐表现。头皮脑电记录中的发作放电提示右侧颞区起源,放电快速波及全脑导联,发作早期为多导联的高波幅棘波节律,频率随后逐渐变慢并向尖波节律演变,到发作晚期可见典型棘慢复合波节律及高波幅慢波活动,随后放电突然终止,整个放电过程持续约41-98秒。IEDs表现为定位于右侧颞区的伴或不伴慢波的棘波放电。硬膜下电极记录的棘波放电较头皮电极记录的放电更为局限。在慢性期发现除外右侧颞区放电以外,对侧颞区也出现独立发放的棘波放电。结论:恒河猴杏仁核经储液囊重复注射KA后,脑电图可捕捉到自发性癫痫发作(Spontaneous Recurrent Seizures,SRSs)。其发作表现与临床上颞叶癫痫患者的颞叶失神及口咽部自动症具有一定的相似性。后期对侧大脑半球局灶性棘波放电的出现提示该模型癫痫样放电呈现进展性的特点,这与人类颞叶癫痫的临床特征相似。
[Abstract]:Background: epilepsy is a common chronic nervous system disease. A lot of achievements have been made in the study of epileptogenic mechanism and sudden onset mechanism by using epileptic animal model. However, rodent model is the main research at present. It is different from human species. It is difficult to replicate human epileptic neural network and related symptoms, so it is necessary to construct a primate epileptic animal model to provide the basis for the study of epileptic network. This study intends to use brain stereotaxic technique to plant amygdaloid nucleus. Into the microcatheter and subcutaneous liquid storage sac, The chronic temporal lobe epilepsy model of rhesus monkey was established by repeated injection of kainic AcidKAK, a epileptic agent, through the liquid storage sac. Objective: to explore the method of establishing non-human primate chronic temporal lobe epilepsy animal model and to evaluate the effect of the model making. Methods: firstly, the right amygdaloid nucleus was implanted into the right amygdala by using stereotactic technique, and the microcatheter was connected with the subcutaneous liquid storage sac. The video EEG was injected into the liquid storage sac under the video EEG monitoring, and then the video EEG was monitored two weeks later. If the EEG records neither the interictal Epileptiform dischargeses nor the seizure discharges in the interictal epileptiform discharges, Two of the animals were selected to bury bilateral subdural electrodes, and the intracranial EEG was monitored regularly. Results: during the injection of Ka into the amygdala, the EEG records of the scalp showed no obvious discharges. After many injections of Ka, the animals recorded IEDsand captured the complete discharge during the attack period. During the attack, the animals showed stupefaction, looked around blankly, and occasionally suffered from oral and facial automatism (chewing, licking tongue, etc.). The seizure and discharge recorded in the scalp EEG showed the origin of the right temporal region, the rapid spread of the discharge to the whole brain, and the high amplitude spike rhythm of multiple leads in the early stage of the attack. The frequency then became slower and gradually changed to the sharp wave rhythm. At the end of the attack, typical spike and slow complex wave rhythm and high amplitude slow wave activity were observed, and then the discharge suddenly stopped. The whole discharge lasted about 41-98 seconds. The IEDs showed spike discharge with or without slow waves located in the right temporal region. The spike discharge recorded by the subdural electrode was more limited than that recorded by the scalp electrode, except in the chronic phase. Outside the right temporal region, The contralateral temporal region also showed an independent spike discharge. Conclusion: after repeated injection of Ka into the amygdala of rhesus monkey, Electroencephalogram (EEG) can capture the spontaneous epileptic seizure of Spontaneous Recurrent Seizuresus Sss.It has some similarities with clinical temporal lobe epilepsy patients' temporal lobe aphasia and oropharynx automatism. The focal spike discharge in the contralateral hemisphere of the brain is observed in the late stage. It is suggested that epileptiform discharges in this model are progressive. This is similar to the clinical features of human temporal lobe epilepsy.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.1;R-332

【参考文献】