Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats

被引:86
作者
Kanazawa, Masato [1 ]
Miura, Minami [1 ]
Toriyabe, Masafumi [1 ]
Koyama, Misaki [1 ]
Hatakeyama, Masahiro [1 ]
Ishikawa, Masanori [1 ]
Nakajima, Takashi [2 ]
Onodera, Osamu [1 ]
Takahashi, Tetsuya [1 ]
Nishizawa, Masatoyo [1 ]
Shimohata, Takayoshi [1 ]
机构
[1] Niigata Univ, Brain Res Inst, Dept Neurol, Chou Ku, 1-757 Asahimachi Dori, Niigata, Japan
[2] Natl Hosp Org, Niigata Natl Hosp, Dept Neurol, 3-52 Akasaka Cho, Kashiwazaki, Niigata, Japan
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
ENDOTHELIAL GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; NEURAL STEM-CELLS; MAC-1; CD11B/CD18; AXONAL OUTGROWTH; STROKE; ANGIOGENESIS; PLASTICITY; VEGF; MACROPHAGES;
D O I
10.1038/srep42582
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-beta 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.
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页数:16
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