Jing Meng, Shingo Tetsuro, Yasuhara Takao, Kondo Akihiko, Morimoto Takamasa, Wang Feifei, Baba Tanefumi, Yuan Wen Ji, Tajiri Naoki, Uozumi Takashi, Murakami Mayu, Tanabe Mariko, Miyoshi Yasuyuki, Zhao Shiguang, Date Isao
Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1, Shikata-cho, Okayama 700-8558, Japan.
Brain Res. 2009 Oct 27;1295:203-17. doi: 10.1016/j.brainres.2009.07.079. Epub 2009 Jul 30.
Adult neural stem cells (NSCs) possess the potentials to self-renew and exert neuroprotection. In this study, we examined whether adult NSCs had anti-epileptic effects in rats with status epilepticus (SE) induced by kainic acid (KA) and whether co-administration of erythropoietin (EPO) enhanced anti-epileptic effects or cell survival. Adult NSCs were transplanted into KA-lesioned hippocampus with or without intracerebroventricular EPO infusion. Electronic encephalography (EEG) was recorded for 3 weeks after transplantation. The frequency of abnormal spikes in rats with NSC transplantation decreased significantly compared to those of rats without NSC transplantation. Most of the transplanted NSCs differentiated into GFAP-positive astrocytes. EPO infusion significantly enhanced the survival of NSCs, but not neuronal differentiation or migration. NSC transplantation increased the number of neuropeptide Y (NPY) and glutamic acid decarboxylase 67 (GAD67)-positive interneurons. NSC transplantation also suppressed mossy fiber sprouting into the inner molecular layer with subsequent reduction of hippocampal excitability, which finally prevented the development of spontaneous recurrent seizures in adult rats after KA-induced SE. This study might shed light on the cytoarchitectural mechanisms of temporal lobe epilepsy as well as clarify the effect of adult NSC transplantation with intracerebroventricular EPO infusion for temporal lobe epilepsy.
成年神经干细胞（NSCs）具有自我更新和发挥神经保护作用的潜能。在本研究中，我们检测了成年神经干细胞对海人酸（KA）诱导的癫痫持续状态（SE）大鼠是否具有抗癫痫作用，以及联合应用促红细胞生成素（EPO）是否能增强抗癫痫作用或提高细胞存活率。将成年神经干细胞移植到KA损伤的海马体中，同时或不进行脑室内EPO输注。移植后3周记录脑电图（EEG）。与未移植神经干细胞的大鼠相比，移植神经干细胞的大鼠异常棘波频率显著降低。大多数移植的神经干细胞分化为胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞。EPO输注显著提高了神经干细胞的存活率，但对神经元分化或迁移没有影响。神经干细胞移植增加了神经肽Y（NPY）和谷氨酸脱羧酶67（GAD67）阳性中间神经元的数量。神经干细胞移植还抑制了苔藓纤维向分子内层的发芽，随后降低了海马体的兴奋性，最终预防了KA诱导的SE成年大鼠自发性反复癫痫发作的发生。本研究可能有助于揭示颞叶癫痫的细胞结构机制，并阐明脑室内输注EPO联合成年神经干细胞移植治疗颞叶癫痫的效果。
