title: Targeting CD36-mediated inflammation reduces acute brain injury in transient, but not permanent, ischemic stroke.
abstract: OBJECTIVE
  The pathology of stroke consists of multiple pro-death processes, and CD36 has been suggested as a multimodal target to reduce oxidative stress and inflammation in ischemic stroke. Using CD36-deficient mice and SS-31, a cell permeable tetrapeptide known to down-regulate CD36 pathways, the current study investigated whether targeting CD36 is effective in transient and permanent ischemic stroke.
  
  
  METHODS
  Wild-type or CD36-deficient mice were subjected to either 30-min transient or permanent focal ischemic stroke. In parallel, a cohort of mice subjected to either transient or permanent stroke received either vehicle or 5 mg/kg of SS-31. Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2, mRNA levels, and infarct volume and percent hemispheric swelling were measured in the postischemic brain.
  
  
  RESULTS
  CD36 deficiency or SS-31 treatment significantly attenuated MCP-1 or CCR2 mRNA up-regulation and injury size in the transient ischemic stroke. However, the approaches failed to show the protective effect in permanent ischemic stroke.
  
  
  CONCLUSIONS
  The study revealed that targeting CD36 has a beneficial effect on transient but not permanent focal ischemic stroke. The study thus precludes a generalized strategy targeting CD36 in ischemic stroke and suggests careful consideration of types of stroke and associated pathology in developing stroke therapies.
authors.affiliation: Burke-Cornell Medical Research Institute, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Tolhurst
authors.forename: Hazel H
authors.initials: HH
authors.lastname: Szeto
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018955:CD36 Antigens / Q000172:deficiency* / Q000235:genetics; D018932:Chemokine CCL2 / Q000378:metabolism; D015331:Cohort Studies; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D054390:Receptors, CCR2 / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
chemical_list: D018955:CD36 Antigens; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018696:Neuroprotective Agents; D009842:Oligopeptides; D012333:RNA, Messenger; D054390:Receptors, CCR2; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide
keywords: CD36; Inflammation; Permanent focal ischemia; SS-31; Transient focal ischemia