| First Author | Mohan S | Year | 2018 |
| Journal | Front Neurosci | Volume | 12 |
| Pages | 556 | PubMed ID | 30233287 |
| Mgi Jnum | J:276071 | Mgi Id | MGI:6313823 |
| Doi | 10.3389/fnins.2018.00556 | Citation | Mohan S, et al. (2018) Genetic Deletion of PGF2alpha-FP Receptor Exacerbates Brain Injury Following Experimental Intracerebral Hemorrhage. Front Neurosci 12:556 |
| abstractText | Background: The release of inflammatory molecules such as prostaglandins (e.g., PGF2alpha) is associated with brain damage following an intracerebral hemorrhagic (ICH) stroke; however, the role of PGF2alpha 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 PGF2alpha-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 PGF2alpha 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. |
