高频振荡和极高频振荡在创伤后癫痫发生过程中的动态学变化及其对癫痫发生的意义

Posttraumatic epilepsy (PTE) refers to a chronic recurrent seizure disorder often caused by traumatic brain injury (TBI). TBI is estimated to cause 20% of all symptomatic epilepsies, and population-based studies of newly diagosed epilepsy suggest that up to 5% of all new cases are attributed to TBI. The incidence of PTE after TBI is about 5%. At present, there is no reliable biomarker for predicting the risk of PTE. The timing to intervene for prophylaxis and how to identify the ongoing epileptogenesis is still less known. Clinical trials with antiepileptic drugs (AEDs) have consistently failed to prevent or modify TBI-induced epileptogenesis. Moreover, chronic recurrent seizures that develop as a result of TBI are often pharmaco-resistant to the currently available AEDs. Clinical studies and animal experiments have demonstrated that there is a close relationship among high frequency oscillations (HFOs), very high frequency oscillations (VHFOs) and localization for epileptogenic zone and epileptogenesis. In this study, subdural and depth electrodes would be implanted in ipsilateral parietal region adjacent the injured cortical area and hippocampal dentate gyrus as well as in the contralateral parietal region in TBI-induced lateral fluid-perfusion brain injury in Sprague-Dawley rat. Vedio-electroencephalographic monitoring would be carried out for monitoring the animal behaviour and EEG activity as experimental paradigm. In order to explore the dynamic changes of high frequency activites after TBI, off-line analysis would be done for HFOs and VHFOs. The mossy fiber sprouting and cell loss in the hippocampal and traumatic cortical as well as subcortical areas would be quantitatively evaluated by Timm's staining and thionining after VEEG monitoring is finished. The pathogenesis of PTE would be probably uncovered in some extent by the dynamic changes in spontaneous recurrent seizures, HFOs, VHFOs, as well as histological abnormality after LFP-induced TBI in rat.

创伤后癫痫（PTE）占所有症状性癫痫的20% ，占所有新诊断癫痫病例的5%。目前，尚缺乏一个可靠的生物学标志用于预测PTE。对预防性干预的时机或如何识别癫痫发生，知之甚少。多种抗癫痫药物（AEDs）均不能防止或修饰PTE，且PTE对AEDs表现出抗药性。高频振荡（HFOs）与极高频振荡（VHFOs）与致痫区定位和癫痫发生高度相关。LFP诱发大鼠PTE的临床特征及病理学异常与临床PTE相似。本研究采用LEP诱发大鼠TBI模型，放置皮层或深部电极，通过视频脑电图监测动物行为及脑电活动，采用零相位数字滤波器分析处理脑电信号，并进行高频振荡节律自动检测，提取HFOs和VHFOs，通过Timm和Thionin染色评估海马及创伤局部区域苔藓纤维增生及细胞丧失，揭示自发性反复发作性癫痫发作、HFOs、VHFOs、海马区和创伤局部区域组织病理学的动态学变化，从而揭示PTE的发病机制。

创伤后癫痫（PTE）占所有症状性癫痫的20% ，占所有新诊断癫痫病例的5%。目前，尚缺乏一个可靠的生物学标志用于预测PTE。对预防性干预的时机或如何识别癫痫发生，知之甚少。多种抗癫痫药物（AEDs）均不能防止或修饰PTE，且PTE对AEDs表现出抗药性。高频振荡（HFOs）与极高频振荡（VHFOs）与致痫区定位和癫痫发生高度相关。LFP诱发大鼠PTE的临床特征及病理学异常与临床PTE相似。本研究分为两部分，第一部分为动物实验，采用LEP诱发大鼠TBI模型，放置皮层或深部电极，通过视频脑电图监测动物行为及脑电活动，采用零相位数字滤波器分析处理脑电信号，并进行高频振荡节律自动检测，提取HFOs和VHFOs，通过Timm和Thionin染色评估海马及创伤局部区域苔藓纤维增生及细胞丧失，揭示自发性反复发作性癫痫发作、HFOs、VHFOs、海马区和创伤局部区域组织病理学的动态学变化。第二部分为临床病例采集及分析，选择因肿瘤、外伤、脑血管病等位于大脑功能区病变而需要手术的患者，针对术后不同部位存在的脑软化灶、致痫灶进行高频宽带电生理分析，探讨这些区域在术后不同时间脑电活动的动态变化，从临床角度探讨上述区域损伤后癫痫的发病机制。