Targeting CD36‐Mediated Inflammation Reduces Acute Brain Injury in Transient, but not Permanent, Ischemic Stroke

Summary Aims 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, t...

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Bibliographic Details
Published in:CNS neuroscience & therapeutics 2015-04, Vol.21 (4), p.385-391
Main Authors: Kim, Eun‐Hee, Tolhurst, Aaron T., Szeto, Hazel H., Cho, Sung‐Hee
Format: Article
Language:English
Subjects:
Animals
Brain - drug effects
Brain - immunology
Brain - pathology
Brain Ischemia - drug therapy
Brain Ischemia - immunology
Brain Ischemia - pathology
CD36
CD36 Antigens - deficiency
CD36 Antigens - genetics
Chemokine CCL2 - metabolism
Cohort Studies
Disease Models, Animal
Infarction, Middle Cerebral Artery
Inflammation
Male
Mice, Inbred C57BL
Mice, Knockout
Neuroprotective Agents - pharmacology
Oligopeptides - pharmacology
Original
Permanent focal ischemia
Random Allocation
Receptors, CCR2 - metabolism
RNA, Messenger - metabolism
SS‐31
Stroke - drug therapy
Stroke - immunology
Stroke - pathology
Transient focal ischemia
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Summary:Summary Aims 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. Conclusion 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.
ISSN:1755-5930
1755-5949
DOI:10.1111/cns.12326