Importantly, we find that MG-mediated modulation of MG phenotypes plays an important role in ameliorating delayed tPA-exacerbated ischemic brain injury, because the knockdown of IFNAR1 specifically in MG abrogates the effect of IFNβ on modulating MG polarization, abolishes the protective effect of IFNβ on ameliorating brain injury, and partly reverses the beneficial effect of IFNβ on lessening BBB disruption in delayed tPA-treated MCAO animals. Here, PLAT is linked to brain injury.