Inducible nitric oxide synthase and estradiol exhibit complementary neuroprotective roles after ischemic brain injury

Candice M. Brown, Christopher D. Dela Cruz, Enhua Yang, Phyllis M. Wise

    Research output: Contribution to journalArticle

    Abstract

    Estradiol-17β exerts profound neuroprotective actions following cerebral ischemia through multiple molecular mechanisms. To examine the putative anti-inflammatory mechanisms employed by estradiol during stroke, we explored the interactions between estradiol and inducible nitric oxide synthase (iNOS) in both wildtype and iNOS knockout (iNOSKO) female mice following permanent middle cerebral artery occlusion (MCAO). Female mice were ovariectomized and treated with estradiol. One week later, they were subjected to MCAO, and then killed 24 h later. Analysis of total, cortical and striatal infarct volumes confirmed that estradiol is neuroprotective in wildtype mice. Infarct volumes were also significantly smaller in female iNOSKO female mice, but estradiol did not further decrease injury. We found that one mechanism by which estradiol may act is by decreasing nitric oxide synthase 2 gene expression in the cortex and in the striatum of wildtype mice. These results show that the pro-inflammatory actions of iNOS exacerbate stroke-induced injury within the cortex and striatum, and that iNOS deletion is neuroprotective in ovariectomized and estrogen-replaced female mice.

    Original languageEnglish (US)
    Pages (from-to)782-787
    Number of pages6
    JournalExperimental Neurology
    Volume210
    Issue number2
    DOIs
    StatePublished - Apr 1 2008

    Keywords

    • Estradiol
    • Estrogen
    • Inflammation
    • Ischemia
    • Middle cerebral artery occlusion
    • Nitric oxide synthase
    • Stroke
    • iNOS

    ASJC Scopus subject areas

    • Neurology
    • Developmental Neuroscience

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