Differential sensitivity to induction of spreading depression by partial disinhibition in chronically epileptic human and rat as compared to native rat neocortical tissue
Differential sensitivity to induction of spreading depression by partial disinhibition in chronically epileptic human and rat as compared to native rat neocortical tissue
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DOI：
10.1016/s0006-8993(03)02600-3
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发表时间：
2003-06-13
期刊：
影响因子：
2.9
通讯作者：
Speckmann, E
中科院分区：
文献类型：
--
作者：
Köhling, R;Koch, UR;Speckmann, E
扩散性抑制（SD）的特征是神经元功能的短暂崩溃，伴随着离子稳态的大规模失败。这是一种可以通过提高兴奋性在新皮层组织中诱导的现象，例如注射K+、应用多巴胺能激动剂或阻断Na+/K+ ATP酶。在这里，我们报告了一种新的方法，SD诱导使用最小的去抑制与应用低浓度（5 μ M）的GABA（A）受体阻断剂荷包牡丹碱。这一程序，而亚阈值癫痫样活动容易诱导自发SD在本地大鼠新皮层切片，伴随着典型的去极化的神经元和神经胶质细胞。相反，在癫痫手术获得的人类新皮层标本中，用此剂量的荷包牡丹碱时，约有20%的切片出现自发性癫痫样活动，而无SD。在人体组织中将荷包牡丹碱的浓度提高到致痫剂量（10 μ M）也仅导致癫痫样活动的产生。同样，在匹鲁卡品治疗的慢性癫痫大鼠的脑片中，荷包牡丹碱也仅诱导癫痫样活动而不引起SD。实验表明，慢性癫痫引起对部分GABA（A）受体阻滞剂的敏感性差异，与SD的诱导有关。(C)2003 Elsevier Science B. V.保留所有权利。
Spreading depression (SD) is characterized by a transient breakdown of neuronal function concomitant with a massive failure of ion homeostasis. It is a phenomenon that can be induced in neocortical tissue by raising excitability, e.g. injection of K+, application of glutamatergic agonists, or blocking Na+/K+ ATPase. Here we report a novel method of SD induction using minimal disinhibition with application of low concentrations (5 muM) of the GABA(A) receptor blocker bicuculline. This procedure-while subthreshold for epileptiform activity-readily induced spontaneous SDs in native rat neocortical slices, accompanied by typical depolarizations of neurons and glial cells. In contrast, in human neocortical preparations obtained from epilepsy surgery, in similar to20% of the slices spontaneous epileptiform activity appeared with this bicuculline dosage without SDs. Raising the concentration of bicuculline to an epileptogenic dose (10 muM) in human tissue also resulted in the generation of epileptiform activity only. Likewise, in slices from pilocarpine-treated, chronically epileptic rats, bicuculline also only induced epileptiform activity without eliciting SDs. The experiments indicate that chronic epilepsy causes a differential sensitivity to partial GABA(A) receptor blockade with regard to induction of SD. (C) 2003 Elsevier Science B.V. All rights reserved.