title: Fasudil Enhances Therapeutic Efficacy of Neural Stem Cells in the Mouse Model of MPTP-Induced Parkinson's Disease.
abstract: 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.
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Yan-Hua
authors: YH
authors: Li
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Jing-Wen
authors: JW
authors: Yu
authors: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors: Jian-Yin
authors: JY
authors: Xi
authors: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors: Wen-Bo
authors: WB
authors: Yu
authors: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China.
authors: Jian-Chun
authors: JC
authors: Liu
authors: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China.
authors: Qing
authors: Q
authors: Wang
authors: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China.
authors: Li-Juan
authors: LJ
authors: Song
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Ling
authors: L
authors: Feng
authors: Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors: Ya-Ping
authors: YP
authors: Yan
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, 19107, PA, USA.
authors: Guang-Xian
authors: GX
authors: Zhang
authors: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. bgxiao@shmu.edu.cn.
authors: Bao-Guo
authors: BG
authors: Xiao
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China. macungen2001@163.com.|"2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China. macungen2001@163.com.
authors: Cun-Gen
authors: CG
authors: Ma
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D010302:Parkinson Disease, Secondary; D013378:Substantia Nigra / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C049347:fasudil
keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Bone marrow-neural stem cells; Parkinson’s disease (PD); Rho kinase inhibitor fasudil