Effect of dietary genistein on functional recovery and chronic post-stroke inflammation in ovariectomized middle-aged rats

PURPOSE: Increasing age increases stroke risk in women after menopause. A drop in circulating estrogens after menopause has been described as a key reason for this age-related risk, considering that estrogen has shown neuroprotection preclinically. However, using estrogen therapy for chronic prevention of cardiovascular diseases is limited by inconsistent beneficial and detrimental outcomes. For this, other agents are investigated as alternatives to protect women against changes that come with aging and low estrogen concentrations. In this study, we hypothesized that genistein, a neuroprotective plant-derived estrogen will confer neuroprotection following hypogonadism and experimental stroke. METHOD: We used ovariectomized proven retired breeder Sprague-Dawley rats (aged ~9months old), categorized into two hypogonadal time points (2weeks=short-term deprivation(STD) and 12 weeks=long-term deprivation(LTD)) and treated with isoflavone-free diet, genistein diet(GEN) or 17-β estradiol(E2) implant. Animals were subjected to intraluminal middle cerebral artery occlusion or sham surgery followed by motor and cognitive behavioral tests and biochemical analyses for chronic post-stroke inflammation. RESULTS: Sham-operated animals showed locomotor symmetry after both STD and LTD. Both GEN and E2 improved locomotor symmetry after LTD. GEN but not E2 improved cognitive flexibility after STD. Both GEN and E2 reduced activated calcium-binding adaptor molecule 1(Iba1) after STD. GEN but not E2 increased transforming growth factor-β1 and growth-associated protein at the contralateral hemisphere of stroke after STD. CONCLUSION: Dietary Genistein may improve locomotor function in the acute phase of stroke following LTD, improve aspects of cognition and reduce inflammation after STD.