| Topiramate Treatment Protects Blood-Brain Barrier Pericytes from Hyperglycemia-Induced Oxidative Damage in Diabetic Mice. | |
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MedLine Citation:
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PMID: 22109883 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Diabetes mellitus causes cerebral microvasculature deterioration and cognitive decline. The specialized endothelial cells of cerebral microvasculature comprise the blood-brain barrier, and the pericytes (PC) that are in immediate contact with these endothelial cells are vital for blood-brain barrier integrity. In diabetes, increased mitochondrial oxidative stress is implicated as a mechanism for hyperglycemia-induced PC loss as a prerequisite leading to blood-brain barrier disruption. Mitochondrial carbonic anhydrases (CA) regulate the oxidative metabolism of glucose and thus play an important role in the generation of reactive oxygen species and oxidative stress. We hypothesize that the inhibition of mitochondrial CA would reduce mitochondrial oxidative stress, rescue cerebral PC loss caused by diabetes-induced oxidative stress, and preserve blood-brain barrier integrity. We studied the effects of pharmacological inhibition of mitochondrial CA activity on streptozotocin-diabetes-induced oxidative stress and PC loss in the mouse brain. At 3 wk of diabetes, there was significant oxidative stress; the levels of reduced glutathione were lower and those of 3-nitrotyrosine, 4-hydroxy-2-trans-nonenal, and superoxide dismutase were higher. Treatment of diabetic mice with topiramate, a potent mitochondrial CA inhibitor, prevented the oxidative stress caused by 3 wk of diabetes. A significant decline in cerebral PC numbers, at 12 wk of diabetes, was also rescued by topiramate treatment. These results provide the first evidence that inhibition of mitochondrial CA activity reduces diabetes-induced oxidative stress in the mouse brain and rescues cerebral PC dropout. Thus, mitochondrial CA may provide a new therapeutic target for oxidative stress related illnesses of the central nervous system. |
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Authors:
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Tulin O Price; Vijay Eranki; William A Banks; Nuran Ercal; Gul N Shah |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-22 |
Journal Detail:
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Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Endocrinology (T.O.P., V.E., G.N.S.), Department of Internal Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, Missouri 63104; Veterans Affairs Puget Sound Health Care Center/Geriatric Research Education and Clinical Centers, S-182 (W.A.B.), Seattle, Washington 98108; and Department of Chemistry (N.E.), Missouri University of Science and Technology, Rolla, Missouri 65409. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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