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将 GABA 能药物微注射到丘脑前核可调节匹罗卡品诱导的癫痫发作和癫痫持续状态。

Microinjection of GABAergic agents into the anterior nucleus of the thalamus modulates pilocarpine-induced seizures and status epilepticus.

机构信息

Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil.

出版信息

Seizure. 2010 May;19(4):242-6. doi: 10.1016/j.seizure.2010.02.010. Epub 2010 Mar 27.

DOI:10.1016/j.seizure.2010.02.010
PMID:20347349
Abstract

The anterior nucleus of the thalamus (AN) has been suggested as a potential target for seizure modulation in animal models and patients with refractory epilepsy. We investigate whether microinjections of GABAergic agonists into the AN were protective against pilocarpine-induced generalized seizures and status epilepticus (SE). Rats were treated with bilateral AN injections of muscimol (160 or 80 nmol), bicuculline (15 nmol), or saline (controls) 20 min prior to pilocarpine administration (350 mg/kg i.p.). Electrographic recordings were used to confirm seizure activity. We found that pretreatment with AN muscimol 160 nmol increased the latency to seizures and SE by 2.5-3.0-fold. This dose however was associated with side effects, particularly hypotonia. AN bicuculline was proconvulsant, whereas no major effect was observed after muscimol 80 nmol injections. The percentage of animals that developed SE was similar across groups. Overall, microinjection of high doses of muscimol into the AN delayed the occurrence of pilocarpine-induced seizures and SE but was not able to prevent these events.

摘要

丘脑前核(AN)被认为是动物模型和耐药性癫痫患者癫痫发作调节的潜在靶点。我们研究了将 GABA 能激动剂微注射到 AN 是否对匹鲁卡品诱导的全身性癫痫发作和癫痫持续状态(SE)具有保护作用。在给予匹鲁卡品(350mg/kg,ip)之前 20 分钟,大鼠接受双侧 AN 注射肌肉醇(160 或 80nmol)、比卡鲁胺(15nmol)或生理盐水(对照)。使用脑电图记录来确认癫痫发作活动。我们发现,AN 肌肉醇 160nmol 的预处理将癫痫发作和 SE 的潜伏期延长了 2.5-3.0 倍。然而,该剂量与副作用有关,特别是低张力。AN 比卡鲁胺具有致惊厥作用,而肌肉醇 80nmol 注射后则没有明显作用。发生 SE 的动物百分比在各组之间相似。总体而言,将高剂量肌肉醇微注射到 AN 中延迟了匹鲁卡品诱导的癫痫发作和 SE 的发生,但不能预防这些事件。

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