Estrogen Modulation of Cerebrovascular Inflammation ...



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Estrogen Modulation of Cerebrovascular Inflammation: Changes with Increasing Age

Christa Osuna

Mentors: Sue Duckles, Diana Krause & Lorraine Sunday

Menopause is marked by decline in a woman’s production of estrogen; however, it is unclear if this decline contributes to increased chances of stroke. Although this hormone can regulate stroke-associated inflammation in cerebral vessels, it is unknown if it has the same effect with increased age. This study examined the effect(s) of estrogen on pro-inflammatory mechanisms in cerebral vessels: NFκB translocation, induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and production of nitric oxide (NO) and prostaglandin E2 (PGE2). Three-month and 12-month female rats were used. Each age category contained two groups: ovariectomized and ovariectomized with estrogen treatment for four weeks. Vascular inflammation was induced using lipopolysaccharide (LPS), both in vivo and in vitro. DNA binding assays measuring the NF(B subunit p65 indicate that 12-month animals have more nuclear NFκB activity than 3-month animals. The estrogen-treated groups of both ages showed lower levels of NF(B activity than the untreated groups. Western blots indicated that LPS upregulation of iNOS and COX-2 was markedly increased at 12 months compared to three months. Estrogen decreased the levels of inflammatory mediators in 3-month rats, but had less of an effect at 12 months. These results suggest estrogen has significant anti-inflammatory effects in the cerebrovasculature of young, but not in middle-aged, animals where the inflammatory response is greater. Thus estrogen in pre-menopausal women may be protective against stroke, but changes in the blood vessels resulting from age may prevent estrogen from providing its anti-inflammatory effects in the cerebrovasculature of older women.

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