Influence of ovarian hormone deprivation length on the neuroprotective effects of genistein in stroke (2018)

Purpose: Estrogen deprivation increases the risk of stroke, cardiovascular disease, and cognitive decline in women. Studies in rats demonstrate that the beneficial effects of estrogen in the brain are lost 10 weeks after Ovx. Similar effects are seen in women after several years without estrogen. Thus, most benefits require early intervention with hormones after menopause. Unfortunately, estrogens also have undesirable effects (such as breast cancer) that lead women to alternative treatments for menopause, including plant estrogens such as genistein. Natural products are perceived to be safe even though their benefits are not well established. This project sought to investigate genistein’s ability to protect the brain at varying lengths of ovarian hormone deprivation. Hypothesis: Dietary genistein will maintain the ability to provide neuroprotection in the brain and improve functional recovery after long-term hormone deprivation associated with ovariectomy (Ovx).

Method: Adult female Sprague-Dawley rats (n=6-8) were bilaterally ovariectomized and randomly assigned to 2- (Short, ST) or 12-weeks (Long, LT) estrogen deprivation before starting diets with no isoflavone or genistein (500 ppm) for the rest of the study. After 6 weeks on diets, all rats were subjected to 60 minutes transient middle cerebral artery occlusion (MCAO) or sham surgery. Neurological (neuroscore), motor (rotarod) and cognitive function (Morris water maze, MWM) were used to assess post-MCAO function over 21 days. Rats were humanely euthanized for biochemical and histological follow-up. Data was assessed with 2-way ANOVA and significance set at p

Results: Neuroscore showed a significant effect of stroke, but not diet, in both ST and LT with the LT group performing worse than the ST group (P=0.06). Rotarod showed a significant effect of stroke, but not diet, on learning phase performance for the ST group and a significant interaction between diet and stroke on the learning phase in the LT group. Comparison between ST and LT stroke subgroups showed a significant effect of diet in the learning phase of rotarod. MWM tests are ongoing and suggest that genistein improves performance in the ST groups. Conclusion: Results from these preliminary studies suggest that long-term estrogen deprivation enhances the detrimental behavioral effects of stroke. In sensory-motor assessments, dietary genistein had little effect but may be beneficial for post-stroke cognitive behavior.