Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model
Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model
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DOI：
10.1016/s0014-4886(03)00086-4
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发表时间：
2003-07-01
影响因子：
5.3
通讯作者：
Dingledine, R
中科院分区：
文献类型：
--
作者：
Borges, K;Gearing, M;Dingledine, R
癫痫的啮齿动物匹罗卡品模型表现出海马硬化和自发性癫痫发作，因此类似于人类颞叶癫痫。使用许多可用的小鼠突变体来研究这种癫痫模型将受益于详细的神经病理学研究。为了确定癫痫发生的新特征，我们在CF 1和C5713 L/6小鼠中研究了毛果芸香碱诱导癫痫持续状态（SE）后海马的神经胶质和神经元病理学特征。SE后17-27天，所有CF 1小鼠均显示自发性癫痫发作。到第6天，肺门神经元几乎完全丧失，但锥体细胞死亡的程度在小鼠中差异很大。在苔藓纤维途径，神经肽Y（NPY）持续上调开始1天后SE，31天后在颗粒上层的NPY免疫反应表明苔藓纤维发芽。β 2微球蛋白阳性的激活的小胶质细胞，在没有SE的大脑中通常是不存在的，在3- 31天内在神经元丢失的区域变得丰富，包括海马和杏仁核。受损区域10天后发生星形胶质细胞增生。10天时丘脑中的淀粉样前体蛋白免疫反应性表明延迟的轴突变性。在来自杰克逊实验室的C57 BL/6小鼠中，毛果芸香碱注射后的死亡率非常高，而来自Charles River的小鼠则不高，这表明C57 BL/6（JAX）品系的突变小鼠将难以在毛果芸香碱模型中进行研究，尽管它们的神经病理学与CF 1小鼠相似。先前未在啮齿动物毛果芸香碱模型中研究的主要神经病理学变化包括广泛的小胶质细胞活化、延迟的丘脑轴突死亡和苔藓纤维中的持续性NPY上调，这些变化共同揭示了广泛和持续的胶质细胞以及神经元病理学。(C)2003 Elsevier Science（美国）。All rights reserved.
The rodent pilocarpine model of epilepsy exhibits hippocampal sclerosis and spontaneous seizures and thus resembles human temporal lobe epilepsy. Use of the many available mouse mutants to study this epilepsy model would benefit from a detailed neuropathology study. To identify new features of epileptogenesis, we characterized glial and neuronal pathologies after pilocarpine-induced status epilepticus (SE) in CF1 and C5713L/6 mice focusing on the hippocampus. All CF1 mice showed spontaneous seizures by 17-27 days after SE. By 6 It there was virtually complete loss of hilar neurons, but the extent of pyramidal cell death varied considerably among mice. In the mossy fiber pathway, neuropeptide Y (NPY) was persistently upregulated beginning 1 day after SE; NPY immunoreactivity in the supragranular layer after 31 days indicated mossy fiber sprouting. beta2 microglobulin-positive activated microglia, normally absent in brains without SE, became abundant over 3-31days in regions of neuronal loss, including the hippocampus and the amygdala. Astrogliosis developed after 10 days in damaged areas. Amyloid precursor protein immunoreactivity in the thalamus at 10 days suggested delayed axonal degeneration. The mortality after pilocarpine injection was very high in C57BL/6 mice from Jackson Laboratories but not those from Charles River, suggesting that mutant mice in the C57BL/6(JAX) strain will be difficult to study in the pilocarpine model, although their neuropathology was similar to CF1 mice. Major neuropathological changes not previously studied in the rodent pilocarpine model include, widespread microglial activation, delayed thalamic axonal death, and persistent NPY upregulation in mossy fibers, together revealing extensive and persistent glial as well as neuronal pathology. (C) 2003 Elsevier Science (USA). All rights reserved.