抑制超急性期M1小胶质细胞的迁移可改善大脑中动脉闭塞大鼠的预后。
Inhibiting the Migration of M1 Microglia at Hyperacute Period Could Improve Outcome of tMCAO Rats.
作者信息
Huang Ming, Wan Yan, Mao Ling, He Quan-Wei, Xia Yuan-Peng, Li Man, Li Ya-Nan, Jin Hui-Juan, Hu Bo
机构信息
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Neurology, Institute of Neural Regeneration and Repair, The First Hospital of Yichang, Three Gorges University College of Medicine, Yichang, China.
出版信息
CNS Neurosci Ther. 2017 Mar;23(3):222-232. doi: 10.1111/cns.12665. Epub 2016 Dec 19.
AIM
To study whether inhibiting microglia migration to the ischemic boundary zone (IBZ) at the early phase could improve neurological outcomes after stroke.
METHODS
The transient middle cerebral artery occlusion (tMCAO) was induced in adult male Sprague-Dawley rats. AMD3100, a highly selective CXC-chemokine receptor 4 (CXCR4) antagonist, was used to inhibit microglia migration. Microglia was evaluated by immunofluorescence in vivo, and their migration was tested by transwell assay in vitro. Expressions of cytokines were detected by real-time PCR. Infarct volume was determined by triphenyltetrazolium chloride (TTC) staining. Functional recovery of tMCAO rats was evaluated by behavior tests.
RESULTS
M1 microglia in the IBZ was rapidly increased within 3 days after tMCAO, accompanied with enhanced expression of CXCR4. Chemokine CXC motif chemokine ligand 12 (CXCL12) was also increased in the IBZ. And AMD3100 could obviously decline M1 microglia migration induced by CXCL12 and secretion of related inflammatory cytokines in the IBZ after stroke. This was accompanied by significant attenuated infarct volume and improved neurological outcomes.
CONCLUSION
This study confirms the protective efficacy of inhibiting microglia migration at the hyperacute phase as a therapeutic strategy for ischemic stroke in tMCAO model of rats, and its therapeutic time window could last for 24 h after cerebral ischemia reperfusion.
目的
研究在早期抑制小胶质细胞向缺血边界区（IBZ）迁移是否能改善中风后的神经功能结局。
方法
对成年雄性Sprague-Dawley大鼠进行短暂性大脑中动脉闭塞（tMCAO）。使用高度选择性的CXC趋化因子受体4（CXCR4）拮抗剂AMD3100抑制小胶质细胞迁移。通过体内免疫荧光评估小胶质细胞，并通过体外transwell实验检测其迁移情况。通过实时PCR检测细胞因子的表达。用氯化三苯基四氮唑（TTC）染色测定梗死体积。通过行为测试评估tMCAO大鼠的功能恢复情况。
结果
tMCAO后3天内，IBZ中的M1小胶质细胞迅速增加，同时CXCR4表达增强。趋化因子CXC基序趋化因子配体12（CXCL12）在IBZ中也增加。AMD3100可明显减少中风后CXCL12诱导的M1小胶质细胞迁移以及IBZ中相关炎性细胞因子的分泌。这伴随着梗死体积显著减小和神经功能结局改善。
结论
本研究证实了在超急性期抑制小胶质细胞迁移作为大鼠tMCAO模型缺血性中风治疗策略的保护效果，其治疗时间窗可在脑缺血再灌注后持续24小时。
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