Faculty of Graduate Studies, Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
Med Sci Monit. 2018 Jan 8;24:161-169. doi: 10.12659/msm.907758.
BACKGROUND This study was designed to investigate the potential anticonvulsant and neuroprotective effects of methylene blue (MB) on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation (BLA) in Wistar rats. MATERIAL AND METHODS The rats were randomly divided into 4 groups: (1) the Control group (rats without any treatment); (2) the Sham group (rats received electrode implantation but without electrical stimulation); (3) the SSSE group (rats received electrode implantation and additional electrical stimulation); and (4) the SSSE+MB group (rats received 1 mg/kg MB intraperitoneal injection 5 min after SSSE). SSSE models were established by prolonged BLA stimulation. The severities of SSSE were assessed by the number of separate seizures and the accumulated time of seizures. The variations of malondialdehyde/glutathione (MDA/GSH) were assessed 24 h after the establishment of SSSE. Nissl staining was performed to detect the surviving neurons in hippocampal CA1 and CA3 regions, and Western blotting assays were used to detect Caspase-3 (CASP3), B cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX). RESULTS Compared with the SSSE group, treatment with MB (1) markedly reduced the number and accumulated time of seizure activities; (2) significantly attenuated the increase of MDA and the decrease of GSH hippocampal levels; (3) markedly improved the cell morphology and alleviated the neuronal loss in hippocampal CA1 and CA3 regions; (4) significantly attenuated the increase of CASP3 and BAX and the decrease of BCL2 hippocampal levels. CONCLUSIONS MB has a protective effect in the SSSE model and may be useful as an adjuvant for preventing or treating epilepsy in humans.
本研究旨在探讨亚甲蓝（MB）对慢性外侧杏仁核刺激（BLA）诱导的持续癫痫状态（SSSE）的潜在抗惊厥和神经保护作用。
将大鼠随机分为 4 组：（1）对照组（未接受任何治疗的大鼠）；（2）假手术组（接受电极植入但无电刺激的大鼠）；（3）SSSE 组（接受电极植入和附加电刺激的大鼠）；（4）SSSE+MB 组（SSSE 后 5 分钟给予 1mg/kg MB 腹腔注射的大鼠）。通过 BLA 长时间刺激建立 SSSE 模型。通过单独发作次数和发作累积时间评估 SSSE 的严重程度。在建立 SSSE 24 小时后评估丙二醛/谷胱甘肽（MDA/GSH）的变化。用尼氏染色检测海马 CA1 和 CA3 区存活神经元，用 Western blot 检测 Caspase-3（CASP3）、B 细胞淋巴瘤 2（BCL2）和 BCL2 相关 X 蛋白（BAX）。
与 SSSE 组相比，MB 治疗（1）显著减少了发作活动的次数和累积时间；（2）显著减轻了海马 MDA 升高和 GSH 降低；（3）明显改善了海马 CA1 和 CA3 区的细胞形态，减轻了神经元丢失；（4）显著减轻了海马 CASP3 和 BAX 升高和 BCL2 降低。
MB 对 SSSE 模型具有保护作用，可作为预防或治疗人类癫痫的辅助药物。
