| 3-Bromo-7-nitroindazole attenuates brain ischemic injury in diabetic stroke via inhibition of endoplasmic reticulum stress pathway involving CHOP. | |
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MedLine Citation:
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PMID: 22075494 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims The role of nitric oxide (NO) and endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of cerebral ischemic/reperfusion (I/R) injury and diabetes. The aim of the study was to investigate the neuroprotective potential of 3-bromo-7-nitroindazole (3-BNI), a potent and selective neuronal nitric oxide synthase (nNOS) inhibitor against ER stress and focal cerebral I/R injury associated with comorbid type 2 diabetes in-vivo. Main methods Type 2 diabetes was induced by feeding high-fat diet and streptozotocin (35mg/kg) treatment in rats. Focal cerebral ischemia was induced by 2h middle cerebral artery occlusion (MCAO) followed by 22h of reperfusion. Immunohistochemistry and western blotting methods were employed for the detection and expression of ER stress/apoptosis markers [78kDa glucose regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)]. TUNEL assay for DNA fragmentation was also performed. Key findings The diabetic rats subjected to cerebral I/R had prominent neurological damage and functional deficits compared with sham-operated rats. Massive DNA fragmentation was observed in ischemic penumbral region of diabetic brains. Concomitantly, the enhanced immunoreactivity and expression of ER stress/apoptosis markers were noticed. 3-BNI (30mg/kg, i.p.) treatment significantly inhibited the cerebral infarct, edema volume and improved functional recovery of neurological deficits. The neuroprotection was further evident by lesser DNA fragmentation with a concomitant reduction of GRP78 and CHOP. Significance The study demonstrates the neuroprotective potential of 3-BNI in diabetic stroke model which may be partly due to inhibition of ER stress pathway involving CHOP. |
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Authors:
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Krishnamoorthy Srinivasan; Shyam S Sharma |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-29 |
Journal Detail:
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Title: Life sciences Volume: - ISSN: 1879-0631 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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