rTMS通过GSK-3β/β-Catenin通路调控脑梗死大鼠内源性神经干细胞行为的机制研究

A variety of dysfunction has been usually left after cerebral infarction. Repeated transcranial magnetic stimulation (rTMS) is an important clinical non-invasive rehabilitation therapy. The current clinical study and our previous study found that rTMS can promote functional recovery after cerebral infarction, which may be related to neural stem cell (NSCs) activation, but its mechanism has not yet elucidated. In our previous experiment, rTMS could improve the neurological function in rats after cerebral ischemia, mediate endogenous NSCs’ behaviors of proliferation, migration and differentiation, and promote the expression of β-Catenin in cell nucleus. GSK-3β/β-Catenin signal pathway has been shown to regulate the behavior of endogenous NSCs. Therefore, we hypothesize that rTMS could improve neurological function and mediate endogenous NSCs proliferation, migration and differentiation possibly via GSK-3β/β-Catenin signal pathway in ischemic rats. In this study, rTMS will be used as an intervention to identify its effects on functional recovery, to observe the behavior of endogenous NSCs and to explore the role of GSK-3β/β-Catenin signaling pathway in cerebral ischemia rats. The results may contribute to elucidate the benefits of rTMS on neurological function on the molecular level and offer theoretical basis for rTMS treatment in clinical medcine.

脑梗死后常遗留各种功能障碍，重复经颅磁刺激（rTMS）是临床重要的非创性康复治疗手段。目前临床研究及我们前期研究发现rTMS可促进脑梗死后的功能恢复，这可能与神经干细胞（NSCs）激活有关，但其机制尚未阐明。我们前期实验发现，rTMS可促进脑梗死大鼠内源性NSCs的增殖、迁移和分化，上调细胞核内β-Catenin的表达。相关研究提示，GSK-3β/β-Catenin信号通路可调控内源性NSCs的行为。据此，我们假设：rTMS可能通过GSK-3β/β-Catenin信号通路调控内源性NSCs的增殖、迁移和分化，改善脑梗死大鼠的神经功能。本研究以rTMS为干预手段，观察其对脑梗死大鼠神经功能和内源性NSCs行为的影响，并探讨GSK-3β/β-Catenin信号通路在其中的作用，旨在从分子层面阐明rTMS促进脑梗死后神经功能恢复的机制，这将为临床开展rTMS治疗提供理论依据。

脑梗死是常见病、多发病，常遗留各种功能障碍，给家庭和社会带来沉重的负担。重复经颅磁刺激（rTMS）是临床重要的非创性康复治疗手段。目前多项临床研究发现rTMS可促进脑梗死后的功能恢复，这可能与神经干细胞（NSCs）的激活与增殖有关。我们前期实验发现，高频rTMS可促进脑梗死大鼠内源性NSCs的增殖，上调细胞核内β-Catenin的表达，但具体机制不明。本项目在前期研究的基础上，采用体内外两种方式验证高频rTMS对tMCAO或OGD模型后大鼠内源性NSC增殖的影响，以及探讨PI3K/AKT/β-catenin信号通路在其中的作用。研究结果发现：10 Hz rTMS ①可以改善脑梗死大鼠神经功能；②可以促进脑梗死大鼠梗死周围区的NSCs的增殖；③可通过激活PI3K/AKT/β-catenin信号通路促进内源性NSCs的增殖。本研究充分证明了高频rTMS促进脑梗死大鼠神经功能恢复的机制与其上调PI3K/AKT/β-catenin通路，进而调控内源性NSCs的增殖有关。此研究结果对指导脑卒中康复治疗及优化康复策略具有重要意义。