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Introduction: Ischemic stroke results in activation of microglia, which may polarize towards a pro-inflammatory (M1) phenotype and/or an anti-inflammatory (M2) phenotype. Enhancer of zeste homolog (EZH) 2 is a histone-lysine N-methyltransferase enzyme, a key modulator of microglia polarization. We here investigated whether microglial-specific deletion of EZH2 leads to a beneficial protective effect in stroke and microglial over-expressing microglial EZH2 exacerbates stroke outcome in vivo.

Methods: Aged male mice were subjected to 60-minutes middle cerebral artery stroke. Tamoxifen administration was started 30 days prior to stroke to induce genetic deletion of microglial EZH2 in CX3CR1-creER/EZH2-floxed mice. EZH2 floxed mice were used as controls. Microglial EZH2 over-expressing was performed using lentiviral vectors. Mice were sacrificed for immunohistochemistry and crystal violet staining (brain …