Jigar Pravinchandra Modi1, Payam M Gharibani2, Zhiyuan Ma2, Rui Tao3, Janet Menzie4, Howard Prentice5, Jang-Yen Wu6. 1. College of Medicine, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States; Centre for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States. 2. College of Medicine, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States. 3. College of Medicine, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States; Program in Integrative Biology, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States. 4. Program in Integrative Biology, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States. 5. College of Medicine, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States; Program in Integrative Biology, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States; Centre for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States. 6. College of Medicine, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States; Program in Integrative Biology, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States; Centre for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States; China Medical University, Taichung, Taiwan. Electronic address: jwu@fau.edu.
Abstract
BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.