Inhibiting the Migration of M1 Microglia at Hyperacute Period Could Improve Outcome of tMCAO Rats
Inhibiting the Migration of M1 Microglia at Hyperacute Period Could Improve Outcome of tMCAO Rats
复制标题
抑制超急性期 M1 小胶质细胞的迁移可以改善 tMCAO 大鼠的预后。
DOI：
10.1111/cns.12665
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发表时间：
2017-03-01
影响因子：
5.5
通讯作者：
Hu, Bo
中科院分区：
文献类型：
--
作者：
Huang, Ming;Wan, Yan;Hu, Bo
目的研究早期抑制小胶质细胞向缺血边界区（ischemic boundary zone，IBZ）迁移是否能改善脑卒中后神经功能的恢复。AMD3100是一种高选择性CXC趋化因子受体4（CXCR4）拮抗剂，用于抑制小胶质细胞迁移。用免疫荧光法检测小胶质细胞的活性，用transwell法检测其迁移能力。实时荧光定量PCR检测细胞因子的表达。通过氯化三苯基四氮唑（TTC）染色测定细胞体积。结果tMCAO后3天内，IBZ内M1小胶质细胞迅速增加，并伴有CXCR 4表达增强。趋化因子CXC基序趋化因子配体12（CXCL12）也在IBZ中增加。AMD3100可明显降低脑卒中后IBZ区CXCL12诱导的M1小胶质细胞迁移及相关炎性细胞因子的分泌。这是伴随着显着衰减的梗死体积和改善neurologicaloutcomes.ConclusionThis研究证实了抑制小胶质细胞迁移在超急性期作为一种治疗策略的缺血性中风大鼠tMCAO模型的保护作用，其治疗时间窗可以持续到脑缺血再灌注后24小时。
AimTo study whether inhibiting microglia migration to the ischemic boundary zone (IBZ) at the early phase could improve neurological outcomes after stroke.MethodsThe 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 invivo, and their migration was tested by transwell assay invitro. 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.ResultsM1 microglia in the IBZ was rapidly increased within 3days 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.ConclusionThis 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 24h after cerebral ischemia reperfusion.