The Double Roles of the Prostaglandin E2 EP2 Receptor in Intracerebral Hemorrhage

Background: Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicated 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 proved to modulate numerous cellular and molecular processes by activating EP2 receptor after ICH. Objective: This review aim to discuss the PGE2 biosynthesis, downstream signaling pathway of EP2 receptor and the roles of EP2 receptor in ICH-induced brain damage, targeting to provide a potential effective therapeutic strategy. Methods: A large number of literatures on EP2 receptors and intracerebral hemorrhage were searched in PubMed, Medline, and Ebase. Results: Previous studies showed that EP2 receptor mediated double effects in ICH via activation of different signaling pathway. EP2 receptor could induce neuroprotection, spatial learning, and neuroplasticity via cAMP-PKA signaling pathway, while strengthen inflammation mainly through the cAMP-Epac pathway. In addition, the concentration level of cAMP might be the key factor that decides which downstream signaling pathway would be activated. Conclusion: In different phase of cerebral hemorrhage, EP2 receptor plays diverse effects in brain damage through different downstream signaling pathways.