骨髓源神经干细胞（BM-NSCs）可部分抑制中枢神经系统(CNS)神经变性疾病的发展。然而，由于细胞移植的效率低，病理状态下脑内微环境恶劣，干细胞存活率较低，影响其治疗效果。本课题组发现Rho激酶抑制剂盐酸法舒地尔（Fasudil）具有提升干细胞性能，抑制CNS内炎性反应和改善微环境；而且，鼻腔移植途径可使细胞更多更快地进入CNS。为此，拟以腹腔注射Fasudil作为鼻腔移植（GFP+）BM-NSCs的伴侣，探讨Fasudil联合BM-NSCs对MPTP-PD的治疗效果和机制。效果评价指标包括：行为学；病理学；内源性干细胞动员；神经突触形态和功能保护；CNS内外源性（GFP+）干细胞存活分布及分化；神经递质释放；机制探讨从炎症、氧化应激、神经营养因子、凋亡等方面着手。相信BM-NSCs联合Fasudil直接和间接地产生协同或叠加效应，能显现更加理想的治疗效果，有可能成为PD治疗的潜在方案。

BM-NSCs, upon entering the CNS, can preferentially migrate into disease foci, where they exert therapeutic effects. However, the effect of this therapy is not yet ideal, most likely due to two reasons: 1) the sustained inflammation and oxidation in the disease areas, making a hostile microenvironment for neural cells; 2) the slow migration of NSCs. Therefore, pharmacologic strategies targeting inflammation process and increasing NSC migration efficiency will significantly enhance therapeutic efficacy of NSCs in CNS disorders. Previous studies have demonstrated that Fasudil, a selective inhibitor of Rho kinase activity, exerts neuroprotective effects, and intranasal (i.n.) administration has recently been found to be a more rapid and effective approach to deliver medications or cells into the CNS than other routes, e.g., oral, i.v. or i.p. .Based on these interesting knowledges, we will in this project explore the efficacy and mechanism of combination of Fasudil with intranasal administartion of BM-NSCs as a novel therapy of MPTP-PD mice. We will study the therapeutic effect by behavioral experiment, dopaminergic neurons surival, α-synuclein accumulation in the substantia nigra (SN) area of brain, endogenous (GFP-) stem cell mobilization, the morphology and function of synapses, neurotransmitter release, and the survival, distribution and differentiation of transplanted (GFP+) BM-NSCs. We then explore the therapeutic mechanism by inflammatory, oxidation stress, neurotrophic factors secret, and apoptosis pathway.. We believe that Fasudil+ nasal delivery of BM-NSCs may be potentially useful therapies that are worth further exploring.