Intracerebral hemorrhage outcomes following selective blockade or stimulation of the PGE2 EP1 receptor

• Published in: BMC neuroscience 2015-08, Vol.16 (1), p.48-48, Article 48
• Main Authors: Leclerc, Jenna L, Ahmad, Abdullah S, Singh, Nilendra, Soshnik-Schierling, Luke, Greene, Ellis, Dang, Alex, Doré, Sylvain
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - immunology; Astrocytes - pathology; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - immunology; Blood-Brain Barrier - pathology; Brain - drug effects; Brain - immunology; Brain - pathology; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - immunology; Cerebral Hemorrhage - pathology; Collagenases; Complications and side effects; COX-2 inhibitors; Disease Models, Animal; Gliosis - drug therapy; Gliosis - immunology; Gliosis - pathology; Hydrazines - pharmacology; Iron - metabolism; Leukocytes - drug effects; Leukocytes - immunology; Leukocytes - pathology; Male; Mice, Inbred C57BL; Microglia - drug effects; Microglia - immunology; Microglia - pathology; Neuroimmunomodulation - drug effects; Neuroimmunomodulation - physiology; Neuroprotective Agents - pharmacology; Oxazepines - pharmacology; Prostaglandins E; Receptors, Prostaglandin E, EP1 Subtype - agonists; Receptors, Prostaglandin E, EP1 Subtype - antagonists & inhibitors; Receptors, Prostaglandin E, EP1 Subtype - metabolism; Recovery of Function - drug effects
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/s12868-015-0182-2

Inflammation following intracerebral hemorrhage (ICH) significantly contributes to secondary brain damage and poor outcomes. Prostaglandin E2 (PGE2) is known to modulate neuroinflammatory responses and is upregulated in response to brain injury as a result of changes in inducible cyclooxygenase 2 (COX-2) and the membrane-bound type of PGE synthase. Inhibition of COX-2 activity has been reported to attenuate ICH-induced brain injury; however, the clinical utility of such drugs is limited due to the potential for severe side effects. Therefore, it is now important to search for downstream targets capable of preferentially modulating PGE2 signaling, and the four E prostanoid receptors, EP1-4, which are the main targets of PGE2, remain a viable therapeutic option. We have previously shown that EP1 receptor deletion aggravates ICH-induced brain injury and impairs functional recovery, thus the current study aimed to elaborate on these results by including a pharmacologic approach targeting the EP1 receptor. Chronic post-treatment with the selective EP1 receptor antagonist, SC-51089, increased lesion volume by 30.1 ± 14.5% (p