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ABSTRACT: 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.
SUBMITTER: Huang M
PROVIDER: S-EPMC6492671 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Huang Ming M Wan Yan Y Mao Ling L He Quan-Wei QW Xia Yuan-Peng YP Li Man M Li Ya-Nan YN Jin Hui-Juan HJ Hu Bo B
CNS neuroscience & therapeutics 20161219 3
<h4>Aim</h4>To study whether inhibiting microglia migration to the ischemic boundary zone (IBZ) at the early phase could improve neurological outcomes after stroke.<h4>Methods</h4>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 ...[more]