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    Nitric oxide formation during cortical spreading depression is critical for rapid subsequent recovery of ionic homeostasis

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    Publication date
    2009-07-27T09:22:56Z
    Author
    Urenjak, Jutta A.
    Obrenovitch, Tihomir P.
    Wang, M.
    Keyword
    Spreading depression
    Nitric oxide
    Nitric oxide synthase
    L-NAME
    Migraine
    Sroke
    N-methyl-d-aspartate
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Cortical spreading depression (CSD) is a temporary disruption of local ionic homeostasis that propagates slowly across the cerebral cortex. Cortical spreading depression promotes lesion progression in experimental stroke, and may contribute to the initiation of migraine attacks. The purpose of this study was to investigate the roles of the marked increase of nitric oxide (NO) formation that occurs with CSD. Microdialysis electrodes were implanted in the cortex of anesthetized rats to perform the following operations within the same region: (1) elicitation of CSD by perfusion of high K+ medium; (2) recording of CSD elicitation; (3) application of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME); and (4) recording of dialysate pH changes. The primary effect of L-NAME (0.3 to 3.0 mmol/L in the perfusion medium) was a marked widening of individual CSD wave, resulting essentially from a delayed initiation of the repolarization phase. This change was due to NO synthase inhibition because it was not observed with the inactive isomer D-NAME, and was reversed by L-arginine. This effect did not appear to be linked to the suppression of a sustained, NO-mediated vascular change associated with the superposition of NO synthase inhibition on high levels of extracellular K+. The delayed initiation of repolarization with local NO synthase inhibition may reflect the suppression of NO-mediated negative feedback mechanisms acting on neuronal or glial processes involved in CSD genesis. However, the possible abrogation of a very brief, NO-mediated vascular change associated with the early phase of CSD cannot be ruled out.
    URI
    http://hdl.handle.net/10454/3117
    Version
    No full-text available in the repository
    Citation
    Obrenovitch, T.P., Urenjak, J.A. and Wang, M. (2002). Nitric oxide formation during cortical spreading depression is critical for rapid subsequent recovery of ionic homeostasis. Journal of Cerebral Blood Flow & Metabolism. Vo. 22, No. 6, pp. 680-688.
    Link to publisher’s version
    http://www.nature.com/jcbfm/journal/v22/n6/pdf/9591259a.pdf
    Type
    Article
    Collections
    Life Sciences Publications

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