title: Prostaglandin E2 EP4 Receptor Activation Attenuates Neuroinflammation and Early Brain Injury Induced by Subarachnoid Hemorrhage in Rats.
abstract: Activation of E prostanoid 4 receptor (EP4) shows neuroprotective effects in multiple central nervous system (CNS) lesions, but the roles of EP4 receptor in subarachnoid hemorrhage (SAH) are not explored. This study was designed to research the effects of EP4 modulation on early brain injury (EBI) after experimental SAH in rats. We found that the administration of EP4 selective agonist AE1-329 significantly improved neurological dysfunction, blood brain barrier (BBB) damage and brain edema at 24 h after SAH. Furthermore, AE1-329 obviously reduced the number of activated microglia and the mRNA and protein levels of pro-inflammatory cytokines, and increased Ser1177 phosphorylated endothelial nitric oxide synthase (Ser1177 p-eNOS). Moreover, AE1-329 significantly reduced the number of TUNEL-positive cells and active caspase-3 in cortex after SAH. The EP4 selective antagonist AE3-208 was also administrated and the opposite effects were achieved. Our results indicate that activation of EP4 protects brain from EBI through downregulating neuroinflammation reaction after SAH.
authors.affiliation: Department of Neurosurgery, Huzhou Central Hospital, 198 Hongqi Lane, Huzhou, 313003, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Zhejiang Chinese Medicine University, 54 Youdian Lane, Hangzhou, 310006, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Huzhou Central Hospital, 198 Hongqi Lane, Huzhou, 313003, China. yanai71@163.com.
authors.forename: Ai
authors.initials: A
authors.lastname: Yan
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D058309:Receptors, Prostaglandin E, EP4 Subtype
keywords: EP4 receptor; Early brain injury; Inflammation; Subarachnoid hemorrhage