2017.02.15
Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats
（Sci Rep. 2017 Feb 14;7:42582. doi: 10.1038/srep42582.）
Kanazawa M1, Miura M1, Toriyabe M1, Koyama M1, Hatakeyama M1, Ishikawa M1, Nakajima T2, Onodera O1, Takahashi T1, Nishizawa M1, Shimohata T1
1Department of Neurology, Brain Research Institute, Niigata University
2Department of Neurology, Niigata National Hospital, National Hospital Organization
Abstract
Cell-therapies that invoke pleiotropic mechanisms may facilitate functional recovery in stroke patients. We hypothesized that a cell therapy using microglia preconditioned by optimal oxygen-glucose deprivation (OGD) is a therapeutic strategy for ischemic stroke because optimal ischemia induces anti-inflammatory M2 microglia. We first delineated changes in angiogenesis and axonal outgrowth in the ischemic cortex using rats. We found that slight angiogenesis without axonal outgrowth were activated at the border area within the ischemic core from 7 to 14 days after ischemia. Next, we demonstrated that administration of primary microglia preconditioned by 18 hours of OGD at 7 days prompted functional recovery at 28 days after focal cerebral ischemia compared to control therapies by marked secretion of remodelling factors such as vascular endothelial growth factor, matrix metalloproteinase-9, and transforming growth factor-β polarized to M2 microglia in vitro/vivo. In conclusion, intravascular administration of M2 microglia preconditioned by optimal OGD may be a novel therapeutic strategy against ischemic stroke.
