Oleoylethanolamide protects against ischemic stroke by modulating microglia M1/M2 polarization in PPARα-dependent manner

OBJECTIVE Oleoylethanolamide(OEA) has shown neuroprotective effect in treating acute and chronic ischemic stroke.However,it is unclear whether OEA is able to modulate microglia/macrophage polarization,which has recently been documented to be important in the pathology of ischemic stroke.This study explored the potential role of OEA in modulating the microglial phenotypes.METHODS In vivo,middle cerebral artery occlusion(MCAO) was induced in both PPARα-/-(KO) and wild-type(WT)mice.In vitro,primary cortical microglia or neuron or coculture from KO/WT mice was subjected to oxygen glucose deprivation(OGD).Western blotting and immunofluorescence were used for detecting the specialized protein expression of M1/M2,such as CD206 and CD16/32.q PCR was utilized to detect the signature gene change of M1/M2.RESULTS OEA significantly reduced neuron damage of mice after MCAO.More importantly,OEA promoted microglia/macrophage transferring from inflammatory M1 phenotype to a protective,anti-inflammatory M2 phenotype in vivo or in vitro.Interestingly,these benifical effects of OEA could not be observed in the KO mice or KO microglia.CONCLUSION Our results reveal a novel pharmacological effect of OEA in modulating microglia/macrophage polarization after MCAO,thus depening our understanding of neuroprotective mechanisms of OEA in treatment of ischemic stroke.Furthermore,this new mechanism may allow OEA to be used in many other microglia/macrophage polarizationrelated inflammatory diseases.