Prolonged prophylactic effects of gabapentin on status epilepticus-induced neocortical injury.
Prolonged prophylactic effects of gabapentin on status epilepticus-induced neocortical injury.
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DOI：
10.1016/j.nbd.2020.104949
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发表时间：
2020-08
影响因子：
6.1
通讯作者：
Prince DA
中科院分区：
文献类型：
--
作者：
Perez-Ramirez MB;Gu F;Prince DA
癫痫持续状态 (SE) 的长期后果发生在急性发作后幸存的患者中。我们开发了急性局灶性新皮质 SE (FSE) 的体内模型，以研究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嗪+4-氨基吡啶，在麻醉小鼠中诱导急性 2 小时 FSE 发作。 10 天和 30 天后，使用免疫细胞化学和电生理学技术研究了单次 FSE 的形态和功能后果。结果集中在皮质 V 层，显示星形胶质细胞增生、小胶质细胞增生、神经元密度降低、兴奋性突触增加，以及血小板反应蛋白 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出异常的癫痫样爆发放电，以及 V 层锥体细胞中微型和自发兴奋性突触后电流频率的增加，以及小白蛋白免疫反应性 (PV-IR) 和 V 层锥体细胞中微型抑制性突触后电流频率的降低。使用批准的药物加巴喷丁 (GBP) 治疗（FSE 发作后 ip 100 mg/kg/天，3 次/天，持续 7 天）可预防神经胶质增生、TSP2- 和 α2δ-1- IR 增强以及受影响新皮质中兴奋性突触密度的增加。该模型提供了一种评估 FSE 对新皮质结构和功能的不利影响以及潜在预防性治疗的方法。
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.
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影响因子：
6.1
作者：
Andresen, Lauren;Hampton, David;Taylor-Weiner, Amaro;Morel, Lydie;Yang, Yongjie;Maguire, Jamie;Dulla, Chris G.
通讯作者：
Dulla, Chris G.
影响因子：
2.5
作者：
Faria, Leonardo C.;Prince, David A.
通讯作者：
Prince, David A.
影响因子：
12.7
作者：
Christman, CW;Salvant, JB;Povlishock, JT
通讯作者：
Povlishock, JT
影响因子：
16.2
作者：
Farhy-Tselnicker I;van Casteren ACM;Lee A;Chang VT;Aricescu AR;Allen NJ
通讯作者：
Allen NJ
影响因子：
2.2
作者：
Friedman, Alon;Kaufer, Daniela;Heinemann, Uwe
通讯作者：
Heinemann, Uwe