Influence of ovarian hormone deprivation length on the neuroprotective effects of genistein in stroke

Abstract

PURPOSE: Advancing age increases women’s susceptibility to stroke compared to men, especially after the menopausal transition. Among the reasons proposed for high stroke incidence in postmenopausal women is a significant decrease in estrogen (E2) concentration, based on well-established evidence that E2 is neuroprotective during ischemia in animal studies. While E2 treatment can be beneficial, extended delays in its replacement can result in detrimental actions on the brain which contributes to widespread mistrust of menopausal hormone therapy. Interest in the beneficial effects of soy isoflavones has grown as a viable alternative for E2. However, results from clinical trials have been inconsistent as there seems to be no consensus on the benefits of soy isoflavones in menopausal women. Notwithstanding, evidence suggests a time-dependent benefit of soy isoflavones, even though there is no systematic assessment in preclinical studies to identify the window of opportunity for their proposed optimal benefits. Hypothesis: After long-term hormone deprivation, the soy isoflavone genistein will maintain the ability to provide neuroprotection in the brain following aging and the loss of endogenous E2 in an experimental stroke model. METHODS: Young adult and retired proven breeder Sprague-Dawley rats ( [greater than] 9 mo) were bilaterally ovariectomized, divided into 2 post-ovariectomized time points (2 and 12 weeks) and fed with an isoflavone free (IF) diet. At the end of each time point, rats were continued on IF diet or switched to genistein diet. Two weeks later, rats underwent transient middle cerebral artery occlusion for 60 mins. After stroke rats were subjected to a series of behavioral tests including neurological function, cylinder test, rotarod, and the Morris Water Maze (MWM). RESULTS:Our results demonstrated a significant effect (p CONCLUSION: Dietary genistein had little effect on the sensorimotor outcomes but holds a promise in improving cognitive function post-stroke in the long term.