Abstract TP114: Histone Deacetylase Inhibitors Panobinostat and Entinostat for Motor Recovery After Ischemic Stroke in Mice
| Autor: | Arumugam V Thiruma, Faisal F Alamri, Vardan T. Karamyan, Abdullah Al Shoyaib, Serob T. Karamyan, Nausheen Syeara, Srinidhi Jayaraman |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Stroke. 51 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/str.51.suppl_1.tp114 |
| Popis: | In this study, we investigated the potential of two histone deacetylase (HDAC) inhibitors, panobinostat and entinostat, to enhance recovery of motor function after ischemic stroke in CD-1 male mice. Panobinostat, which is a pan-HDAC inhibitor, is an FDA-approved drug for certain cancers, whereas entinostat is a class-I HDAC inhibitor and is widely expected to get approval for clinical use in near future. Stroke was induced by photothrombosis and the drugs were administered intraperitoneally every other day (panobinostat at 10 mg/kg or 30 mg/kg; entinostat at 5 mg/kg or 15 mg/kg) starting from day 5 to day 15 after stroke. The control group received only vehicle following the same regimen. In addition, all drug or vehicle-treated mice exercised for 2 hours (voluntary wheel running) starting from day 9 to day 41 after stroke. Additional control groups included sham-operated animals, and mice which had stroke but were not drug/vehicle-treated or allowed to run. Motor function of the mice was evaluated by blinded investigators using gridwalk and cylinder tests before and after stroke. Acetylation of histone 3 in the peri-infarct region of the brain samples was measured by immunoblotting. Our results indicate that lower dose of both panobinostat and entinostat marginally improved motor function in mice by day 42 after stroke, although it did not reach statistical significance. Notably, this improvement trend was lost with the higher dose of both drugs which also showed some toxicity. No statistical difference was observed in running distance of mice among experimental groups. Likewise, we did not observe statistically significant difference in stroke volumes among the experimental groups. Immunoblotting experiments indicated that both panobinostat and entinostat dose-dependently increased the level of acetylated histone in the cortical, peri-infarct region of drug-treated animals compared to the non-treated groups. In summary, our results indicate that both panobinostat and entinostat do not facilitate improvement of motor function after stroke at the tested doses. However, it is likely that lower doses of these drugs may enhance recovery of motor function after stroke. |
| Databáze: | OpenAIRE |
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