Effect of dietary genistein on functional recovery following cerebral ischemia in ovariectomized middle-aged rats




Sumien, Nathalie
Oppong-Gyebi, Anthony
Vann, Philip
Metzger, Daniel
Schreihofer, Derek
Sun, Fen


0000-0002-3535-5886 (Oppong-Gyebi, Anthony)

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PURPOSE: Advancing age increases women's susceptibility to stroke compared to men, after the menopausal transition, which has been attributed mainly to a drop in estrogen concentrations postmenopause. However, time-dependent mixed benefits and detriments of estrogen therapy for prevention of stroke and cardiovascular diseases after menopause have contributed to widespread mistrust of estrogen use. This has led to the use of other agents like soy isoflavones as alternatives to estrogen therapy. In this study, we hypothesized that the neuroprotective effects of genistein, a soy isoflavone following cerebral ischemia are less sensitive to length of hypogonadism than estrogen. METHOD: Proven retired breeder Sprague-Dawley rats (aged ~9 months old) were ovariectomized, grouped into two hypogonadal time points (2weeks= short-term and 12 weeks= long-term) followed by treatment with isoflavone-free diet or genistein diet (GEN). A group that received 17-β estradiol (E2) was introduced as a control for hormone supplementation. All animals underwent middle cerebral artery occlusion or sham surgery followed by behavioral tests including neurological function, motor function with cylinder and rotarod, cognition with Morris Water Maze (MWM) and gait performance with Catwalk test. RESULTS: We observed effect of stroke on motor and gait performances. Effect of treatment and length of hypogonadism were observed on motor, cognitive and gait performances. GEN but not E2 improved spatial learning on the reversal phase of MWM test. CONCLUSION: Dietary GEN may improve forelimb asymmetry in the acute phase of stroke following long-term hypogonadism and aspects of cognitive functions post-stroke.