Effect of fingolimod on oligodendrocyte maturation under prolonged cerebral hypoperfusion.

Effect of fingolimod on oligodendrocyte maturation under prolonged cerebral hypoperfusion. Brain Res. 2019 Jun 12;: Authors: Yasuda K, Maki T, Saito S, Yamamoto Y, Kinoshita H, Kyung Choi Y, Valavan Arumugam T, Lim YA, Li Hsian Chen C, Tsun-Hon Wong P, Ihara M, Takahashi R Abstract Oligodendrocytes (OLGs) support neuronal system and have crucial roles for brain homeostasis. As the renewal and regeneration of OLGs derived from oligodendrocyte precursor cells (OPCs) are inhibited by various pathological conditions, the restoration of impaired oligodendrogenesis is a therapeutic strategy for OLG-related diseases such as subcortical ischemic vascular dementia (SIVD). Fingolimod (FTY720), a drug for multiple sclerosis, is reported to elicit a cytoprotective effect on OPCs in vitro. However, the effects of fingolimod against ischemia-induced suppression of OPC differentiation remain unknown. Hence, the purpose of this study was to investigate the effectiveness of fingolimod against ischemia-induced suppression of oligodendrogenesis. For the in vitro experiments, primary rat cultured OPCs were incubated with a non-lethal concentration of CoCl2 to induce chemical hypoxic conditions and were treated with or without fingolimod-phosphate. We found that low concentration fingolimod-phosphate directly rescued ischemia-induced suppression of OPC differentiation via the phosphoinositide 3-kinase-Akt pathway. For the in vivo experiments, we used a m...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research