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松果体切除及褪黑素治疗对大鼠颞叶癫痫的影响。

Effects of pinealectomy and the treatment with melatonin on the temporal lobe epilepsy in rats.

作者信息

de Lima Eliângela, Soares José Maria, del Carmen Sanabria Garrido Yaima, Gomes Valente Sandra, Priel Margareth Rose, Chada Baracat Edmund, Abrão Cavalheiro Esper, da Graça Naffah-Mazzacoratti Maria, Amado Débora

机构信息

Disciplina de Neurologia Experimental, Universidade Federal de São Paulo-Escola Paulista de Medicina, CEP 04023-900, Edifício Leal Prado, São Paulo, SP, Brazil.

出版信息

Brain Res. 2005 May 10;1043(1-2):24-31. doi: 10.1016/j.brainres.2005.02.027.

Abstract

The aim of the present work was to analyze the effects of pinealectomy in the development of the epilepsy model induced by pilocarpine in adult male rats. Group I: Wistar male adult rats were submitted to pinealectomy, and 7 days after surgery, these animals received pilocarpine (350 mg/kg, i.p.) to induce three distinct behavioral phases: status epilepticus, seizure-free, and chronic phases. This late, as well as all control groups were continuously video-recorded for 60 days, to study behavior parameters. These animals were killed and the brain sections were processed for Nissl and neo-Timm. Group II: Another group, also submitted to pinealectomy, received several injections of melatonin (2.5 mg/kg): 20 min before, concomitantly with pilocarpine, 30 min, 1 h, and 2 h after pilocarpine administration. Some animals from group I and all from group II were sacrificed 48 h following status epilepticus onset to perform TUNEL assay. The latency for status epilepticus onset, status epilepticus length as well as mortality rate during status epilepticus were similar for pinealectomized and control groups. On the other hand, pinealectomized rats presented minor duration of the silent period, a higher number of spontaneous seizures during the chronic phase, increased number of TUNEL-positive cells (acute phase), increased neuronal loss, and marked supragranullar mossy fibers sprouting (chronic phase) in the hippocampal formation, when compared with control groups. Our data show that the pinealectomy facilitates the epileptogenic process that follows the long-lasting status epilepticus. This facilitation can be partially reverted by the simultaneous administration of melatonin.

摘要

本研究的目的是分析松果体切除对成年雄性大鼠匹鲁卡品诱导的癫痫模型发育的影响。第一组:将Wistar成年雄性大鼠进行松果体切除,术后7天,这些动物接受匹鲁卡品(350mg/kg,腹腔注射)以诱导三个不同的行为阶段:癫痫持续状态、无发作期和慢性期。此后,以及所有对照组均连续录像60天,以研究行为参数。这些动物被处死,脑切片进行尼氏染色和新的Timm染色。第二组:另一组同样进行松果体切除的大鼠,在匹鲁卡品给药前20分钟、给药同时、给药后30分钟、1小时和2小时接受多次褪黑素注射(2.5mg/kg)。癫痫持续状态发作后48小时,处死第一组的一些动物和第二组的所有动物,进行TUNEL检测。松果体切除组和对照组在癫痫持续状态发作的潜伏期、癫痫持续状态的时长以及癫痫持续状态期间的死亡率相似。另一方面,与对照组相比,松果体切除的大鼠在海马结构中静息期持续时间较短、慢性期自发癫痫发作次数较多、TUNEL阳性细胞数量增加(急性期)、神经元损失增加以及颗粒上层苔藓纤维明显发芽(慢性期)。我们的数据表明,松果体切除促进了长期癫痫持续状态后的致痫过程。同时给予褪黑素可部分逆转这种促进作用。

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