title: FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms.
abstract: FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4+T cells, macrophages and microglia. Importantly, the CNS of FSD-C10-treated mice showed a shift of activated macrophages/microglia from the type 1 to type 2 status, elevated numbers of oligodendrocyte precursor cells (OPCs) and oligodendrocytes, and increased levels of neurotrophic factors NT-3, GDNF and BDNF. FSD-C10-treated microglia significantly inhibited Th1/Th17 cell differentiation and increased the number of IL-10+CD4+T cells, and the conditioned medium from FSD-C10-treated microglia promoted OPC survival and oligodendrocyte maturation. Addition of FSD-C10 directly promoted remyelination in a chemical-induced demyelination model on organotypic slice culture, in a BDNF-dependent manner. Together, these findings demonstrate that FSD-C10 promotes neural repair through mechanisms that involved both immunomodulation and induction of neurotrophic factors.
authors.affiliation: Institute of Brain Science, Datong key Laboratory of Molecular and Cell Immunology, Shanxi Datong University, Datong, 037009, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Brain Science, Datong key Laboratory of Molecular and Cell Immunology, Shanxi Datong University, Datong, 037009, China.
authors.forename: Hai-Fei
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chai
authors.affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200025, China.
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Thome
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Institute of Brain Science, Datong key Laboratory of Molecular and Cell Immunology, Shanxi Datong University, Datong, 037009, China.|"2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, China.
authors.forename: Cun-Gen
authors.initials: CG
authors.lastname: Ma