Abstract T P241: Deletion of PGE2 EP1 Receptor Results in Reduced Phagocytosis and Exacerbates Hemorrhagic Injury
Background: Spontaneous intracerebral hemorrhage (ICH) is the deadliest and most debilitating form of stroke with a first year mortality rate as high as 50% to 60%. Role of prostaglandin E2 (PGE2) receptor EP1 has been extensively studies in ischemic stroke; however, the precise role of this receptor in intracerebral hemorrhage-induced brain injury is unknown. Therefore, in this study we determined the role of the EP1 receptor in collagenase-induced hemorrhagic stroke.
Methods: ICH was induced randomly in 2.0-2.5 month old male C57BL/6 wildtype (WT) and EP1 knockout (EP1-/-) mice by intrastriatal injection of collagenase. Functional outcomes including neurologic deficits, rotarod performance, open field activity, and adhesive removal performance were evaluated at 72h post ICH. Hematoma volume, and cell survival and death, were assessed using cresyl violet and Fluoro-Jade staining respectively. Microglial activation was estimated using Iba1 immunoreactivity. Phagocytosis was assessed with fluorescently-labeled microspheres injected into the site of the hematoma and at the end of the survival time Iba1 immunoreactivity was used to label cells with microspheres. Values are expressed in (mean±SEM) and the number of cells/field was provided by averaging four different regions surrounding the hematoma.
Results: Following 72h post injury, EP1-/- mice showed worsened outcomes compared to the WT mice. The results revealed elevated neurological and sensorimotor deficits and exacerbated hematoma volume. Fluoro-Jade staining showed significantly increased numbers of degenerating neurons and reduced neuronal survival in EP1-/- as compared with the WT mice. The in vivo phagocytic behavior of microglial cells in WT and EP1-/- suggested that the number of microspheres incorporated into Iba1-positive cells was 145.4±15.4% greater in WT than in EP1-/- mice.
Conclusion: These results suggest that, the deletion of PGE2 EP1 receptor results in augmented hemorrhagic brain injury partially through reduced phagocytosis.[Supported by NIH R01 funds (SD)]
Author Disclosures: N. SIngh: None. B. Ma: None. C.C. Leonardo: None. A.S. Ahmad: None. S. Narumiya: None. S. Dore: None.
- © 2014 by American Heart Association, Inc.