Neuroprotection mediated by the EP4 receptor avoids the detrimental side effects of COX-2 inhibitors following ischaemic injury

► COX-2 inhibition decreased cell death following OGD in vitro and in vivo stroke. ► Activation of the EP4 receptor showed comparable protection in the same models. ► Targeting pathways downstream of COX-2 avoids side effects of COX-2 inhibitors. ► Prostaglandin receptor signalling is a potential therapeutic target for stroke.