Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.



Committee Chair

Corbitt, Cynthia

Author's Keywords

Infarct; Stroke; Menopause; Estrogen; Phytoestrogen; Brain


Estrogen--Physiological effect; Phytoestrogens--Physiological effect; Cerebrovascular disease--Prevention


Premenopausal women have fewer and less severe strokes when compared to postmenopausal females and aged matched males. The most obvious factor that could account for the observed difference is the physiological activity of Estrogen. Numerous studies over the past two decades have investigated estrogen's role as a neuroprotective agent against stroke damage. Many physiological mechanisms have been identified supporting neuroprotection; however, data also exist to suggest that estrogen may be harmful in certain situations such as those that produce high blood levels of estrogen or use estrogen in older models. The Women's Health Initiative (WHI), a large epidemiological study, found that stroke incidence increased in women that were at least one year post menopausal and given hormone replacement therapy (HRT) containing estrogen. This conflicting information surrounding HRT has many women turning to soy-based phytoestrogens as an alternative therapy. Phytoestrogens are compounds made by plants that induce some response traditionally associated with the steroid hormone estradiol. The long term consequences of phytoestrogen consumption are presently unknown. As more postmenopausal women choose to consume high levels of phytoestrogens either via diet or supplements, the question arises as to how estrogen and phytoestrogens interact. The current study is the first to explore the neuroprotective potential of phytoestrogens and the combined effects of estrogen and phytoestrogens against permanent focal ischemia in a middle aged model. It also explores the ability of estrogen and phytoestrogen in regulating apoptotic vs. proliferative pathways in injured neuronal tissue. While estrogen and phytoestrogen did produce similar effects, neither was associated with neuroprotection. This study is important, however, because it adds substance to the growing body of reports that E2 does not mitigate neuronal damage due to primary infarct and it does not positively influence apoptotic pathways in aged female rats. It also provides a more realistic model for putting into context the negative effects documented in epidemiological studies such as the WHI, in which hypoestrogenic women suffered more frequent and detrimental stroke events when given estrogen replacement.