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KCNQ 激活剂氟吡汀对复发性发热性惊厥模型的保护作用。

Protective effect of the KCNQ activator flupirtine on a model of repetitive febrile seizures.

机构信息

Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.

出版信息

Epilepsy Res. 2011 Nov;97(1-2):64-72. doi: 10.1016/j.eplepsyres.2011.07.005. Epub 2011 Aug 9.

Abstract

Activation of KCNQ-channels has been shown to decrease or reduce the propagation of neuronal excitation in the immature central nervous system, and KCNQ activators represent a new class of anticonvulsant compounds. Their effectiveness has been demonstrated in many seizure models but not in repetitive febrile seizures (RFS) models. This study aimed to test whether the KCNQ channel activator flupirtine is also effective for RFS in rats. RFS were induced in Sprague-Dawley (SD) rats at postnatal day 10 (P10) in a warm water bath for eight consecutive days with or without the pre-administration of flupirtine or phenobarbital. As results, both drugs significantly increased the latency and decreased the rate of febrile seizures. Furthermore, seizures in the flupirtine group had a significantly shorter duration and were less severe compared with the phenobarbital group. The flupirtine-treated group showed less impairment in learning and memory and less obvious pathological changes in the brain following RFS compared with the phenobarbital-treated group. In summary, flupirtine appears to be effective in RFS prophylaxis and may merit further study as a candidate for the treatment of RFS in infants and children.

摘要

KCNQ 通道的激活已被证明可以减少或减缓不成熟中枢神经系统中神经元兴奋的传播,KCNQ 激活剂代表了一类新的抗惊厥化合物。它们在许多癫痫发作模型中已被证明有效,但在复发性热性惊厥 (RFS) 模型中尚未得到证实。本研究旨在测试 KCNQ 通道激活剂氟吡汀是否也对大鼠的 RFS 有效。在 P10 天,将 Sprague-Dawley (SD) 大鼠置于温水中诱导 RFS,连续 8 天,或在给予氟吡汀或苯巴比妥之前进行诱导。结果显示,两种药物均显著延长潜伏期并降低发热性惊厥的发生率。此外,与苯巴比妥组相比,氟吡汀组的惊厥持续时间更短,严重程度更低。与苯巴比妥组相比,氟吡汀治疗组在 RFS 后学习和记忆受损程度较轻,大脑的病理变化不明显。综上所述,氟吡汀似乎对 RFS 的预防有效,可能值得进一步研究,作为治疗婴儿和儿童 RFS 的候选药物。

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