Genetic deletion of the prostaglandin E2 E prostanoid receptor subtype 3 improves anatomical and functional outcomes after intracerebral hemorrhage

• Published in: The European journal of neuroscience 2015-05, Vol.41 (10), p.1381-1391
• Main Authors: Leclerc, Jenna L., Lampert, Andrew S., Diller, Matthew A., Doré, Sylvain
• Format: Article
• Language: English
• Subjects: Animals; Blood-Brain Barrier - pathology; Brain - metabolism; Brain - pathology; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cerebral Hemorrhage - metabolism; Cerebral Hemorrhage - pathology; Gene Deletion; gliosis; Gliosis - metabolism; iron; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; mouse; neuroinflammation; neuroprotection; Receptors, Prostaglandin E, EP3 Subtype - genetics; Receptors, Prostaglandin E, EP3 Subtype - metabolism; stroke; Stroke - metabolism; Stroke - pathology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12909

Intracerebral hemorrhage (ICH) is a stroke subtype associated with high mortality and morbidity. Following ICH, excitotoxicity and inflammation significantly contribute to secondary brain injury and poor outcomes. Prostaglandin E2 (PGE2) levels rise locally with insult to the nervous system, and PGE2 is known to modulate these processes mainly through its E prostanoid (EP) receptors, EP1‐4. EP receptor subtype 3 (EP3) is the most abundant EP receptor in the brain and we have previously shown that signaling through the PGE2–EP3 axis exacerbates excitotoxicity and ischemic stroke outcomes. This study aimed to investigate the contribution of this pathway in modulating anatomical outcomes and functional recovery following ICH. Genetic deletion of EP3 resulted in 48.2 ± 7.3% less ICH‐induced brain injury (P