| Autor: |
Mohan S; Department of Pharmaceutical Sciences, Manchester University, College of Pharmacy, Natural and Health Sciences, Fort Wayne, IN, United States., Koller EJ; Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, FL, United States., Fazal JA; Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, FL, United States., De Oliveria G; Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, FL, United States., Pawlowicz AI; Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, FL, United States., Doré S; Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, FL, United States.; Departments of Neurology, Psychiatry, Psychology, Pharmaceutics and Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, College of Medicine, Gainesville, FL, United States. |
| Abstrakt: |
Background: The release of inflammatory molecules such as prostaglandins (e.g., PGF 2α ) is associated with brain damage following an intracerebral hemorrhagic (ICH) stroke; however, the role of PGF 2α and its cognate FP receptor in ICH remains unclear. This study focused on investigating the role of the FP receptor as a target for novel neuroprotective drugs in a preclinical model of ICH, aiming to investigate the contribution of the PGF 2α -FP axis in modulating functional recovery and anatomical outcomes following ICH. Results: Neurological deficit scores in FP -/- mice were significantly higher compared to WT mice 72 h after ICH (6.1 ± 0.7 vs. 3.1 ± 0.8; P < 0.05). Assessing motor skills, the total time mice stayed on the rotating rod was significantly less in FP -/- mice compared to WT mice 24 h after ICH (27.0 ± 7.5 vs. 52.4 ± 11.2 s; P < 0.05). Using grip strength to quantify forepaw strength, results showed that the FP -/- mice had significantly less strength compared to WT mice 72 h after ICH (96.4 ± 17.0 vs. 129.6 ± 5.9 g; P < 0.01). In addition to the behavioral outcomes, histopathological measurements were made. In Cresyl violet stained brain sections, the FP -/- mice showed a significantly larger lesion volume compared to the WT (15.0 ± 2.2 vs. 3.2 ± 1.7 mm 3 ; P < 0.05 mice.) To estimate the presence of ferric iron in the peri-hematoma area, Perls' staining was performed, which revealed that FP -/- mice had significantly greater staining than the WT mice (186.3 ± 34.4% vs. 86.9 ± 13.0% total positive pixel counts, P < 0.05). Immunoreactivity experiments on brain sections from FP -/- and WT mice post-ICH were performed to monitor changes in microgliosis and astrogliosis using antibodies against Iba1 and GFAP respectively. These experiments showed that FP -/- mice had a trend toward greater astrogliosis than WT mice post-ICH. Conclusion: We showed that deletion of the PGF 2α FP receptor exacerbates behavioral impairments and increases lesion volumes following ICH compared to WT-matched controls.Detailed mechanisms responsible for these novel results are actively being pursued. |
