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 language | English (US) |
|---|---|
| Pages (from-to) | 91-99 |
| Number of pages | 9 |
| Journal | Brain research |
| Volume | 1576 |
| DOIs | |
| State | Published - Jan 1 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Protective mechanism of sulindac in an animal model of ischemic stroke
AU - Modi, Jigar Pravinchandra
AU - Mohammadgharibani, Payam
AU - Ma, Zhiyuan
AU - Tao, Rui
AU - Menzie, Janet
AU - Prentice, Howard
AU - Wu, Jang Yen
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Akt Bcl2
KW - Grp-78
KW - Hsp 27
KW - Stroke & Sulindac
UR - http://www.scopus.com/inward/record.url?scp=84926126497&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926126497&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2014.06.019
DO - 10.1016/j.brainres.2014.06.019
M3 - Article
C2 - 24968090
AN - SCOPUS:84926126497
VL - 1576
SP - 91
EP - 99
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -