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单独使用或联合使用地昔帕明和地西泮抑制大鼠癫痫持续状态的疗效。

Efficacy of dapsone administered alone or in combination with diazepam to inhibit status epilepticus in rats.

机构信息

Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Ciudad de México, Mexico; Laboratorio de Neurofarmacología Molecular, Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco Ciudad de México, Mexico.

Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Ciudad de México, Mexico.

出版信息

Brain Res. 2019 Apr 1;1708:181-187. doi: 10.1016/j.brainres.2018.12.017. Epub 2018 Dec 17.

DOI:10.1016/j.brainres.2018.12.017
PMID:30571982
Abstract

Status epilepticus (SE) is a serious medical condition, as it may trigger epileptogenesis. SE produces continuous generalized seizures resulting in irreversible brain damage. Therefore, the use of neuroprotective agents to prevent cell damage, may reduce the impact of SE. The use of diazepam (DZP), has shown limited neuroprotective effect in SE patients. According to previous reports, dapsone (DDS) is able to reduce both cell damage and seizures, when administered 30 min before the onset of seizures. This study is aimed to evaluate the ability of DDS, alone or in combination with DZP starting their administration once the SE is onset to evaluate the control of seizures in rats. Results showed a reduced convulsive electrical activity after 30 min, 1 and 2 h after SE induced by kainic acid (KA) administration, in the animals treated with DZP alone or in combination with DDS. At 24 h, we observed electrical activity similar to baseline in all groups receiving treatment. The animals treated with DDS and DZP alone or in combination showed an increase in the number of viable pyramidal cells but only the combination showed a lower number of damaged pyramidal neurons of hippocampal CA3. In conclusion, DDS plus DZP was able to control SE and to prevent SE-induced damage, when administered in combination with DZP. As DDS is already in use for patients with leprosy, that combination may be a safe, good option for human cases of SE.

摘要

癫痫持续状态(SE)是一种严重的医疗状况,因为它可能引发癫痫发生。SE 会产生持续的全身性癫痫发作,导致不可逆转的脑损伤。因此,使用神经保护剂来防止细胞损伤,可以减轻 SE 的影响。使用地西泮(DZP)在 SE 患者中显示出有限的神经保护作用。根据之前的报告,氨苯砜(DDS)在癫痫发作前 30 分钟给药时,既能减少细胞损伤,也能减少癫痫发作。本研究旨在评估 DDS 单独使用或与 DZP 联合使用,在 SE 发作后开始给药,以评估其对大鼠癫痫发作的控制能力。结果显示,在给予红藻氨酸(KA)诱导 SE 后 30 分钟、1 小时和 2 小时,单独使用 DZP 或与 DDS 联合使用的动物的惊厥性电活动减少。在 24 小时时,所有接受治疗的动物的电活动均恢复到基线水平。单独使用 DDS 和 DZP 或联合使用的动物的存活锥体神经元数量增加,但只有联合使用的动物海马 CA3 区的损伤锥体神经元数量较少。总之,DDS 加 DZP 能够控制 SE 并预防 SE 引起的损伤,当与 DZP 联合使用时。由于 DDS 已用于治疗麻风病患者,因此这种联合用药可能是 SE 人类病例的一种安全、有效的选择。

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