sulindac and Infarction--Middle-Cerebral-Artery

The present study analyzed whether administration of sulindac, a non-steroidal anti-inflammatory drug (NSAID) would prevent, attenuate or repair ischemia induced brain injury and reverse functional impairment in a focal ischemia model of stroke.. Male Sprague-Dawley rats (weight 250-300 g) were subjected to middle cerebral artery occlusion (MCAO). Sulindac was given 2 days before and 24 h after ischemia at 0.2 mg/day with daily injections until sacrifice on day 3 or day 11. Infarct size was measured by TTC staining and western immunoblot was employed.. TTC analysis of brain slices indicated a decrease in infarct size in sulindac treated animals. Western blot results indicated that sulindac induced expression of Hsp 27, a marker of cell stress, in the ischemic penumbra and core on days 3 and 11. Hsp 27 is important as a protective molecular chaperone. Increases were also found in the protective molecules Akt and Bcl-2 in the ischemic penumbra and core following sulindac administration.. Our data indicate that administration of sulindac results in decreased infarct size and that there is a central role for the molecular chaperone Hsp 27, the pro-survival kinase Akt and the anti-apoptotic component Bcl-2 in mediating these protective effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Survival; Disease Models, Animal; Gene Expression Regulation; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Infarction, Middle Cerebral Artery; Male; Nerve Tissue Proteins; Neuroprotective Agents; Premedication; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Sulindac; Up-Regulation