Abstract WMP81: Prostaglandin E2 EP1 Receptor Deletion Exacerbates Brain Injury And Behavioral Deficits After Experimental Induced Intracerebral Hemorrhage.
Background: Prostaglandin E2 (PGE2) has been reported to have various cytoprotective or toxic properties in acute and chronic neurological conditions. The role of the PGE2 EP1 receptor in intracerebral hemorrhage (ICH) induced brain injury has not yet been fully investigated. Thus, this study is performed to investigate the role of the EP1 G-protein-coupled receptor in hemorrhagic stroke.
Methods: ICH was induced randomly in 2.0-2.5 month-old male C57BL/6 (WT) and EP1 knockout mice by intrastriatal injection of collagenase. Following 72h after ICH, neurological outcomes were evaluated using: adhesive removal, rotarod, open field and neurological deficits on a 24-point scale. Thereafter, the mice were sacrificed and brains were taken out to quantify the lesion volume, brain swelling, cell death/survival, and microglial activation following this ICH model. All values are expressed in (mean±SEM), and the number of cells/field was provided by averaging four different regions around the hematoma.
Results: Collagenase injection produced a reproducible hematoma that was primarily restricted to the striatum. Neurological deficit was worsened in EP1 knockout (18.7±1.7) compared to WT mice (11.1±0.9) after 72h of ICH. Interestingly, deletion of EP1 receptor aggravates brain injury lesion volume (17.8±1.7 vs. 12.5±1.6mm3) and brain swelling (18.7±1.6 vs. 11.1±0.9mm3) compared to WT mice. Behavior analysis (EP1 vs. WT) using adhesive removal (91.7±4.3 vs. 52.3±3.9sec), open field (1120.0±155.9 vs. 1837.0±82.8sec), and rotarod performance (46.0±4.2 vs. 66.3±4.0sec) tests indicate that WT mice recovered faster compared to EP1 mice. Fluoro Jade staining indicated that cell death was higher in EP1 than WT mice (117.3±7.3 vs. 71.5±4.6 cells/field), and 8-hydroxyguanosine staining showed that neuronal survival was reduced in EP1 mice (19.4±2.4 vs. 33.9±2.1cells/field) at 72h after ICH. Thereafter, quantification using Iba1 immunostaining demonstrated a 72% increase in the number of immunoreactive microglia appearing in WT than in EP1 mice.
Conclusion: These results suggest that EP1 receptor deletion aggravates brain injury, induces neurological dysfunction with decreased neuronal survival, and activates microglia in this ICH preclinical model.
- © 2012 by American Heart Association, Inc.