Neuroscience
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/29935
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Browsing Neuroscience by Author "Metzger, Daniel"
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Item Chronic testosterone deprivation sensitizes the middle-aged rat brain to damaging effects of testosterone replacement(2020) Vann, Philip; Wong, Jessica; Sumien, Nathalie; Cunningham, Rebecca; Metzger, Daniel; Schreihofer, Derek; Oppong-Gyebi, Anthony; Contreras Garza, Jo; Kasanga, Ella; Smith, CharityHypothesis: We hypothesized that a delay in testosterone replacement therapy (TRT) following castration in middle-aged male rats would result in increased oxidative stress and a reduction in the neuroprotective effects of testosterone following stroke. Background: Levels of the hormone testosterone (T) fall in aging men. Recently, the number of men obtaining TRT has increased dramatically. However, other consequences of aging, such as oxidative stress, may result in detrimental effects when combined with TRT, including stroke risk. Methods: Twelve-month old male Fischer 344 rats were divided into 5 groups (n=9-14): 1) gonad Intact sham stroke (SH), 2) Intact stroke (IN), 3) short term castrate + T (ST), 4) long term castrate (LC), and 5) long term castrate + T (LCT). Rats were castrated 2 weeks (ST) or 10 weeks (LT, LCT) prior to T. Middle cerebral artery occlusion (Stroke) done via stereotaxic injection of endothelin 1 (ET1). Three, 7, and 14 days after stroke several behavior tests were done. Rats were humanely euthanized, and blood/brains were collected. Results: Plasma oxidative stress measured by Advanced Oxidative Protein Products (AOPP) was significantly negatively correlated with T levels. Long-term hypogonadism in middle-aged male Fischer 344 rats TRT exacerbated the detrimental behavioral effects of experimental focal cerebral ischemia. Conclusion: Data suggest that TRT after long-term hypogonadism can exacerbate functional recovery after focal cerebral ischemia.Item Effect of dietary genistein on functional recovery following cerebral ischemia in ovariectomized middle-aged rats(2020) Sumien, Nathalie; Vann, Philip; Metzger, Daniel; Schreihofer, Derek; Sun, Fen; Oppong-Gyebi, AnthonyPURPOSE: 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.