Abstract T P67: The Role of PGF2-alpha FP Receptor in a Mouse Model of Intracerebral Hemorrhage
Background: Prostaglandin F2α (PGF2α) has been described to exert beneficial and detrimental effects in various neurological disorders. Brain damage following an intracerebral hemorrhagic (ICH) stroke is associated with the release of inflammatory molecules such as PGF2α; however, the role of PGF2α and its cognate FP receptor in ICH remains unclear.
Methods: Using age (2.5-3.5 months) and weight-matched (20-30g) adult male WT and FP-/- C57BL/6a single unilateral intrastriatal injection of collagenase VII-S [0.04 Units in 0.2μL saline] was given using specific stereotaxic coordinates. To measure for functional outcomes, neurobehavioral assays were performed 24, 48 and 72h post-ICH. These included neurological deficit scoring (NDS) using a 24-point scale, accelerating speed rotarod test to measure motor deficits and forepaw grip strength (in grams) using a grip strength meter (GSM) to measure of sensorimotor ability.
Results: NDS: 72h after ICH, FP-/- mice showed significantly higher deficits as compared to WT mice (4.6±0.8 vs 0.5±0.4; p<0.01, n=4-8). Rotarod: 24h post-ICH, FP-/- mice showed a greater reduction in the total time on the rotarod as compared to WT mice (36.0±9.8s vs 58.6±7.1s). Forepaw grip strength: FP-/- mice showed a significantly less strength as compared to WT mice at 72h post-ICH (96.4±17.0g vs 129.6±5.9g; p<0.01). Additional studies in process include determining the lesion volume and assessing neuronal death using Cresyl Violet and Fluoro-Jade staining, respectively. In addition to in vivo protocols, in vitro experiments with primary cultures are planned to determine the mechanism responsible for these novel findings.
Conclusion: We have shown that deletion of the FP receptor exacerbates behavioral impairments following ICH compared to WT controls. However, the complete mechanism responsible for these novel results is actively being pursued.
Author Disclosures: S. Mohan: Research Grant; Significant; F32-5FNS078933 (S.M.). S. Narumiya: None. S. Dore: Research Grant; Significant; NS046400 (S.D.).
- © 2014 by American Heart Association, Inc.