BET protein BRD4 as a new therapeutic target in cerebral ischemic stroke

Clinical data have shown the levels of inflammatory markers are associated with the risk of ischemic stroke. The bromodomain-containing protein 4 (BRD4), a bromodomain and extraterminal (BET) family member, is a key factor in regulating nuclear factor kappa B (NF-kappa B) activity. We examined the therapeutic effects of BRD4 inhibitor JQ1 in the middle cerebral artery occlusion (MCAO) model of ischemic stroke in rats. Neurological functions, infarct volume, neuronal apoptosis and neuroinflammatory response were examined 24 h after MCAO. Isolated microglial cells were studied in vitro. Results showed that BRD4 expression was significantly increased in the MCAO group. The neurological damage, infarct volume and neuronal apoptosis were all significantly inhibited in JQ1-treated rats compared to control group following MCAO. Inflammatory responses were also decreased by JQ1. In addition, JQ1 inhibited NF-kappa B activation following MCAO. In vitro, BRD4 silencing decreased the production of proinflammatory cytokines via inhibiting NF-kappa B in microglial cells after OGD/reoxygenation. These findings suggest that BRD4 could be a novel therapeutic target in ischemic stroke.