title: Inhibiting the Migration of M1 Microglia at Hyperacute Period Could Improve Outcome of tMCAO Rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Quan-Wei
authors.initials: QW
authors.lastname: He
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuan-Peng
authors.initials: YP
authors.lastname: Xia
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Li
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001596:Benzylamines; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000080027:Cyclams; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; D017077:Culture Media, Conditioned; D000080027:Cyclams; D016207:Cytokines; D006571:Heterocyclic Compounds; D052247:Nitric Oxide Synthase Type II; C088327:plerixafor
keywords: 
  tMCAO
  ; AMD3100; CXCL12/CXCR4; Hyperacute phase; M1 microglia; Migration