Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Mol Neurobiol. 2017 Sep;54(7):5400-5413. doi: 10.1007/s12035-016-0027-8. Epub 2016 Sep 2.
Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model and explored the possible cellular and molecular mechanisms. The results clearly show that combined treatment of NSCs with fasudil further improves motor capacity of PD mice, thus exerting double effect in treating MPTP-PD. The combined intervention more effectively protected dopaminergic (DA) neurons from loss in the substantia nigra pars compacta (SNpc), which may be associated with the increased number and survival of transplanted NSCs in the brain. Compared with the treatment of fasudil or NSCs alone, the combined intervention more effectively inhibited the activation and aggregation of microglia and astrocytes, displayed stronger anti-inflammatory and antioxidant effects, induced more neurotrophic factor NT-3, and affected the dynamic homeostasis of NMDA and AMPA receptors in MPTP-PD mice. Our study demonstrates that intranasal administration of NSCs, followed by fasudil administration, is a promising cell-based therapy for neuronal lesions.
骨髓源性神经干细胞（NSCs）因其具有修复和再生受损神经元的治疗潜力，是细胞治疗的理想细胞。然而，优化植入细胞和改善中枢神经系统（CNS）的微环境仍然是增强治疗效果的两个关键因素。在本研究中，我们观察了 NSCs 与 fasudil 联合应用于 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病（PD）小鼠模型的联合治疗效果，并探讨了可能的细胞和分子机制。结果清楚地表明，NSCs 与 fasudil 的联合治疗进一步改善了 PD 小鼠的运动能力，从而对 MPTP-PD 发挥了双重治疗作用。联合干预更有效地保护了黑质致密部（SNpc）中多巴胺能（DA）神经元免受损失，这可能与脑内移植的 NSCs 数量增加和存活有关。与 fasudil 或 NSCs 单独治疗相比，联合干预更有效地抑制了小胶质细胞和星形胶质细胞的激活和聚集，表现出更强的抗炎和抗氧化作用，诱导了更多的神经营养因子 NT-3，并影响了 MPTP-PD 小鼠中 NMDA 和 AMPA 受体的动态平衡。我们的研究表明，鼻内给予 NSCs 后给予 fasudil 是一种有前途的神经元损伤的基于细胞的治疗方法。
