Document Detail


More severe type 2 diabetes-associated ischemic stroke injury is alleviated in aldose reductase-deficient mice.
MedLine Citation:
PMID:  20143423     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aldose reductase (AR), the first enzyme in the polyol pathway, has been implicated in a wide variety of physiological and pathological functions, such as diabetic vascular and neural complications. It is known that diabetes mellitus can exacerbate brain and retina damage after ischemic injuries. However, the underlying mechanisms are not clear. In the present study, we made use of db/db mice with an AR null mutation (AR(-/-)db/db) to understand better the role of AR in the pathogenesis of brain and retina ischemic injuries under diabetic conditions. Cerebral and retinal ischemia was induced by transient middle cerebral artery occlusion in control and diabetic mice either with or without an AR null mutation. Mice were evaluated for neurological deficits after 30 min of ischemia and 23.5 hr of reperfusion. Our results showed that the diabetic db/db mice had significantly more severe neurological deficit and larger brain infarct size than the nondiabetic mice. Compared with wild-type db/db mice, the AR(-/-)db/db mice had significantly lower neurological scores, smaller brain infarct areas, and less hemispheric brain swelling. Retinal swelling was also significantly decreased in the AR(-/-)db/db mice. Less swelling in the brain and retina of the AR(-/-)db/db mice correlated with less expression of the water channel aquaporin 4. Taken together, these data clearly show that deletion of AR leads to less severe brain and retinal ischemic injuries in the diabetic db/db mouse. The present study indicates that inhibition of AR in diabetics may protect against damage in the brain and retina following ischemic reperfusion injury.
Authors:
Chung-Man Yeung; Amy C Y Lo; Alvin K H Cheung; Stephen S M Chung; David Wong; Sookja K Chung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  88     ISSN:  1097-4547     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-09-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2026-34     Citation Subset:  IM    
Affiliation:
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Reductase / deficiency,  genetics,  metabolism*
Animals
Aquaporin 4 / metabolism
Blood Glucose / metabolism
Brain / enzymology,  metabolism,  pathology
Brain Ischemia / enzymology*,  metabolism,  pathology
Diabetes Mellitus, Experimental / enzymology,  metabolism,  pathology
Diabetes Mellitus, Type 2 / complications*,  enzymology,  metabolism,  pathology
Infarction, Middle Cerebral Artery / enzymology,  metabolism,  pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Oxidative Stress / physiology
Retina / enzymology,  metabolism,  pathology
Retinal Diseases / enzymology*,  metabolism,  pathology
Severity of Illness Index
Stroke / enzymology*,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/Aqp4 protein, mouse; 0/Aquaporin 4; 0/Blood Glucose; EC 1.1.1.21/Aldehyde Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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