title: Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats.
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.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Toriyabe
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Koyama
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hatakeyama
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Neurology, Niigata National Hospital, National Hospital Organization, 3-52 Akasaka-cho, Kashiwazaki, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Shimohata
mesh_terms: D000818:Animals; D001369:Axons; D015415:Biomarkers; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D017628:Microglia / Q000378:metabolism* / Q000637:transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9; D005947:Glucose; D010100:Oxygen