Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Neurobiol Dis. 2020 Aug;142:104949. doi: 10.1016/j.nbd.2020.104949. Epub 2020 May 19.
Long-term consequences of status epilepticus (SE) occur in a significant proportion of those who survive the acute episode. We developed an in vivo model of acute focal neocortical SE (FSE) to study long-term effects on local cortical structure and function and potential strategies to mitigate adverse consequences of SE. An acute 2 h episode of FSE was induced in anesthetized mice by epidural application of gabazine +4-aminopyridine over sensorimotor neocortex. Ten and 30 days later, the morphological and functional consequences of this single episode of FSE were studied using immunocytochemical and electrophysiological techniques. Results, focused on cortical layer V, showed astrogliosis, microgliosis, decreased neuronal density, and increased excitatory synapses, along with increased immunoreactivity for thrombospondin 2 (TSP2) and α2δ-1 proteins. In addition, neocortical slices, obtained from the area of prior focal seizure activity, showed abnormal epileptiform burst discharges along with increases in the frequency of miniature and spontaneous excitatory postsynaptic currents in layer V pyramidal cells, together with decreases in both parvalbumin immunoreactivity (PV-IR) and the frequency of miniature inhibitory postsynaptic currents in layer V pyramidal cells. Treatment with an approved drug, gabapentin (GBP) (ip 100 mg/kg/day 3×/day for 7 days following the FSE episode), prevented the gliosis, the enhanced TSP2- and α2δ-1- IR and the increased excitatory synaptic density in the affected neocortex. This model provides an approach for assessing adverse effects of FSE on neocortical structure and function and potential prophylactic treatments.
癫痫持续状态（SE）的长期后果在很大比例的存活患者中发生。我们建立了一种体内急性局灶性新皮质 SE（FSE）模型，以研究其对局部皮质结构和功能的长期影响，以及减轻 SE 不良后果的潜在策略。通过在感觉运动新皮质上硬膜外应用加巴喷丁+4-氨基吡啶诱导麻醉小鼠急性 2 小时 FSE 发作。10 天和 30 天后，使用免疫细胞化学和电生理技术研究了这单次 FSE 发作的形态和功能后果。结果主要集中在皮质 V 层，显示出星形胶质细胞增生、小胶质细胞增生、神经元密度降低和兴奋性突触增加，同时血栓素结合蛋白 2（TSP2）和 α2δ-1 蛋白的免疫反应性增加。此外，从先前局灶性癫痫活动区域获得的新皮质切片显示异常癫痫样爆发放电，同时 V 层锥体神经元的微小和自发性兴奋性突触后电流频率增加，而 V 层锥体神经元的 PV-IR 和微小抑制性突触后电流频率降低。使用一种已批准的药物加巴喷丁（GBP）（ip 100mg/kg/天，3×/天，在 FSE 发作后 7 天）治疗可预防受影响新皮质中的神经胶质增生、增强的 TSP2 和 α2δ-1-IR 以及兴奋性突触密度增加。该模型提供了一种评估 FSE 对新皮质结构和功能的不良影响以及潜在预防治疗的方法。
