Neurobiol Dis. 2011 Aug;43(2):312-21. doi: 10.1016/j.nbd.2011.02.013. Epub 2011 Mar 22.
Clinical evidence suggests that febrile status epilepticus (SE) in children can lead to acute hippocampal injury and subsequent temporal lobe epilepsy. The contribution of febrile SE to the mechanisms underlying temporal lobe epilepsy are however poorly understood. A rat model of temporal lobe epilepsy following hyperthermic SE was previously established in our laboratory, wherein a focal cortical lesion induced at postnatal day 1 (P1), followed by a hyperthermic SE (more than 30 min) at P10, leads to hippocampal atrophy at P22 (dual pathology model) and spontaneous recurrent seizures (SRS) with mild visuospatial memory deficits in adult rats. The goal of this study was to identify the long term electrophysiological, anatomical and molecular changes in this model. Following hyperthermic SE, all cortically lesioned pups developed progressive SRS as adults, characterized by the onset of highly rhythmic activity in the hippocampus. A reduction of hippocampal volume on the side of the lesion preceded the SRS and was associated with a loss of hippocampal neurons, a marked decrease in pyramidal cell spine density, an increase in the hippocampal levels of NMDA receptor NR2A subunit, but no significant change in GABA receptors. These findings suggest that febrile SE in the abnormal brain leads to hippocampal injury that is followed by progressive network reorganization and molecular changes that contribute to the epileptogenesis as well as the observed memory deficits.
临床证据表明，儿童热性惊厥持续状态（FS）可导致急性海马损伤和随后的颞叶癫痫。然而，FS 导致颞叶癫痫的机制仍知之甚少。我们实验室之前建立了一种热性 FS 后颞叶癫痫的大鼠模型，其中在出生后第 1 天（P1）诱导局灶性皮质损伤，然后在 P10 时发生热性 FS（超过 30 分钟），导致 P22 时海马萎缩（双重病变模型）和成年大鼠自发性反复性癫痫发作（SRS）伴有轻度视觉空间记忆缺陷。本研究的目的是确定该模型的长期电生理、解剖和分子变化。在热性 FS 后，所有皮质损伤的幼鼠在成年后均逐渐出现 SRS，其特征是海马中出现高度节律性活动。SRS 之前，损伤侧的海马体积减小，并伴有海马神经元丢失、锥体神经元棘突密度显著降低、海马 NMDA 受体 NR2A 亚单位水平升高，但 GABA 受体无明显变化。这些发现表明，异常脑内的热性 FS 导致海马损伤，随后出现进行性网络重组和分子变化，导致癫痫发生以及观察到的记忆缺陷。
