Protective mechanism of sulindac in an animal model of ischemic stroke

Jigar Pravinchandra Modi, Payam Mohammadgharibani, Zhiyuan Ma, Rui Tao, Janet Menzie, Howard Prentice, Jang Yen Wu

Research output: Contribution to journalArticle

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 sulindacresultsindecreasedinfarctsizeandthatthereisacentralroleforthemolecular chaperone Hsp 27, the pro-survival kinase Akt and the anti-apoptotic component Bcl-2 in mediating these protective effects.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalBrain research
Volume1576
DOIs
StatePublished - Jan 1 2014

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Sulindac
Animal Models
Stroke
Ischemia
Western Blotting
Molecular Chaperones
Middle Cerebral Artery Infarction
Brain Injuries
Sprague Dawley Rats
Anti-Inflammatory Agents
Phosphotransferases
Staining and Labeling
Weights and Measures
Injections
Brain
Pharmaceutical Preparations

Keywords

  • Akt Bcl2
  • Grp-78
  • Hsp 27
  • Stroke & Sulindac

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Protective mechanism of sulindac in an animal model of ischemic stroke. / Modi, Jigar Pravinchandra; Mohammadgharibani, Payam; Ma, Zhiyuan; Tao, Rui; Menzie, Janet; Prentice, Howard; Wu, Jang Yen.

In: Brain research, Vol. 1576, 01.01.2014, p. 91-99.

Research output: Contribution to journalArticle

Modi, Jigar Pravinchandra ; Mohammadgharibani, Payam ; Ma, Zhiyuan ; Tao, Rui ; Menzie, Janet ; Prentice, Howard ; Wu, Jang Yen. / Protective mechanism of sulindac in an animal model of ischemic stroke. In: Brain research. 2014 ; Vol. 1576. pp. 91-99.
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