The double roles of the prostaglandin E2 EP2 receptor in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc. PGE2 activates its downstream effects through the G-protein coupled EP receptors, which are classified into four subtypes: EP1, EP2, EP3 and EP4. These receptors have diverse influences on cyclic adenosine monophosphate (cAMP) and phosphoinositol turnover and different anatomical distributions in brain. We focus on the most studied EP2 receptor subtype demonstrated abundantly in cerebral cortex, striatum, and hippocampus. The EP2 receptor possesses both protective and deleterious effects, relying on specific type of damage and the responding components. It has been reported that the PGE2 receptor agonists, for example butaprost, perform a protective effect on ICH-induced brain damage, while some mice lacking EP2 receptor also exhibit less brain injury. This review mainly discusses the PGE2 biosynthesis, downstream signaling pathway of EP2 receptor and mechanisms of the dual roles of the PGE2-EP2 receptor in ICH-induced brain damage, targeting to provide a potential effective therapeutic strategy.