Neuroscience
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21662
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Browsing Neuroscience by Author "Doan, Trinh"
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Item Influence of ovarian hormone deprivation length on the neuroprotective effects of genistein in stroke (2018)(2018-03-14) Metzger, Daniel; Smith, Charity B.S.; Doan, Trinh; Han, Jordan; Schreihofer, Derek; Oppong-Gyebi, AnthonyPurpose: 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.Item The Role of Testosterone Deprivation and Replacement on Stroke Outcome in Middle-Aged Rats(2018-03-14) Han, Jordan; Doan, Trinh; Metzger, Daniel; Oppong-Gyebi, Anthony; Schreihofer, Derek; Smith, Charity B.S.Background: Circulating levels of the steroid hormone testosterone fall in aging men, and in the last decade the number of men obtaining prescriptions for testosterone replacement therapy (TRT) has increased dramatically. However, other consequences of aging, such as increased oxidative stress, may result in detrimental effects when combined with TRT. This include increased risks of thromboembolism and stroke. In women, a delay in hormone therapy (estrogen/progesterone) after menopause results in a loss of benefit for the brain and an increase in risk for stroke and cognitive decline. Whether such a delay would alter the effects of TRT is not known. Hypothesis: In this study, we hypothesized that a delay in 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 (transient cerebral ischemia). Methods: Twelve-month old male Fischer 344 rats were obtained from the National Institutes on Aging. Rats were divided into 5 groups as follows: 1) gonad Intact sham stroke (SHAM), 2) Intact stroke (INT), 3) short term castrate + TRT (STT), 4) long term castrate (LT), and 5) long term castrate + TRT (LTT). Rats were castrated 2 weeks (STT) or 10 weeks (LT, LTT) prior to TRT by subcutaneous silastic capsules containing T. L3T rats were treated with the antioxidant TEMPOL in drinking water starting 2 weeks before TRT. Middle cerebral artery occlusion (Stroke) was accomplished under gas anesthesia by stereotaxic injection of the vasoconstrictor endothelin 1 (ET1) adjacent to the left middle cerebral artery. One, 3, 7, and 14 days after stroke, rats were assessed for neurological deficits using a standardized scoring system. Forelimb bias to the ipsilateral left side was assessed using the cylinder test, and coordinated walking was assessed with an automated ladder walk. Following behavior assessments, rats were humanely euthanized and blood and brains were collected. The effects of stroke and treatments were compared to intact sham stroke (SHAM). Results: Peripheral oxidative stress measured by Advanced Oxidative Protein Products (AOPP) was significantly negatively correlated with T levels, similar to men. ST rats experienced the smallest neurological deficits following stroke, suggesting that