Luongo Roberta, Oliveira Diana Amaral, Lebrun Ivo, Sandoval Maria Regina Lopes
Laboratory of Pharmacology, Butantan Institute, Av. Dr. Vital Brasil, 1500, São Paulo, SP 05503 900, Brazil. roberta
Brain Res Bull. 2009 Jun 30;79(5):296-302. doi: 10.1016/j.brainresbull.2009.04.006. Epub 2009 Apr 23.
We have characterized earlier the long-term behavioural, electroencephalographic and histopatologic features after a single TsTx microinjection, consisting of a neuropeptide isolated from the Tityus serrulatus scorpion venom, into the hippocampus of rats. TsTx was able to induce status epilepticus (SE) and developed later epilepsy. The present study was designed to investigate the outcomes of diazepam plus pentobarbital administered at 30 min, 1, 2 or 6h after the beginning of TsTx-induced SE, on the development of spontaneous recurrent motor seizures (SRMSs), mossy fibre sprouting and hippocampal neurodegeneration in rats. The administration of diazepam (DZ)+pentobarbital (PB) 30 min after the beginning of the TsTx-induced SE was able to markedly reduce the frequency of the SRMSs and prevent the development of mossy fibres sprouting and hippocampal lesion. In the other groups the augment of the extent of hipocampal neurodegeneration, the frequency of SRMSs and degree of aberrant mossy fibre sprouting was directly proportional to the time that the animals were subjected to TsTx-induced SE. In conclusion, our results point out that the early blockade of the TsTx-induced SE with diazepam plus pentobarbital, was effective treatment against later epilepsy development. The effectiveness of this treatment depends on the time that the animals were subjected to the SE. Furthermore, the TsTx model could be a useful tool to study antiepileptogenic drugs in chronic epileptic animals, neuronal degeneration, as well as for the mechanisms underlying epilepsy.
我们之前已经描述了单次向大鼠海马体微量注射TsTx(一种从锯脂鲤蝎毒液中分离出的神经肽)后的长期行为、脑电图和组织病理学特征。TsTx能够诱发癫痫持续状态(SE)并随后引发癫痫。本研究旨在探究在TsTx诱导的SE开始后30分钟、1小时、2小时或6小时给予地西泮加戊巴比妥对大鼠自发性复发性运动性癫痫发作(SRMSs)、苔藓纤维出芽和海马神经变性发展的影响。在TsTx诱导的SE开始后30分钟给予地西泮(DZ)加戊巴比妥(PB)能够显著降低SRMSs的频率,并预防苔藓纤维出芽和海马损伤的发展。在其他组中,海马神经变性程度的增加、SRMSs的频率和异常苔藓纤维出芽的程度与动物遭受TsTx诱导的SE的时间成正比。总之,我们的结果表明,用地西泮加戊巴比妥早期阻断TsTx诱导的SE是预防后期癫痫发展的有效治疗方法。这种治疗的有效性取决于动物遭受SE的时间。此外,TsTx模型可能是研究慢性癫痫动物抗癫痫药物、神经元变性以及癫痫潜在机制的有用工具。