CNS neuroscience & therapeutics · 2016
Inhibiting the Migration of M1 Microglia at Hyperacute Period Could Improve Outcome of tMCAO Rats.
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Huang Ming, Wan Yan, Mao Ling, He Quan-Wei, Xia Yuan-Peng, Li Man, Li Ya-Nan, Jin Hui-Juan, Hu Bo
Аннотация
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.
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.
Предметные рубрики MeSH
AnimalsAnimals, NewbornAnti-HIV AgentsBenzylaminesBrain InfarctionCell HypoxiaCell MovementCell PolarityCells, CulturedCerebral CortexCulture Media, ConditionedCyclamsCytokinesDisease Models, AnimalHeterocyclic CompoundsInfarction, Middle Cerebral ArteryMaleMicrogliaNeuronsNitric Oxide Synthase Type IIRatsRats, Sprague-Dawley