title: Protective mechanism of sulindac in an animal model of ischemic stroke.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Jigar Pravinchandra
authors: JP
authors: Modi
authors: College of Medicine, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States.
authors: Payam M
authors: PM
authors: Gharibani
authors: College of Medicine, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States.
authors: Zhiyuan
authors: Z
authors: Ma
authors: 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.
authors: Rui
authors: R
authors: Tao
authors: Program in Integrative Biology, Florida Atlantic University, Boca Raton, Florida, FL 33431, United States.
authors: Janet
authors: J
authors: Menzie
authors: 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.
authors: Howard
authors: H
authors: Prentice
authors: 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.
authors: Jang-Yen
authors: JY
authors: Wu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011292:Premedication; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013467:Sulindac / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D013467:Sulindac; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C486114:Hspb1 protein, rat; C494920:Akt1 protein, rat
keywords: Akt; Bcl2; Grp-78; Hsp 27; Stroke & Sulindac