Neuroscience
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/29935
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Browsing Neuroscience by Author "Kasanga, Ella"
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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 FDA-approved antibiotic improves motor function in a rat hemi-parkinsonian model: Potential to extend timeline in early-stage Parkinson's disease(2020) Salvatore, Michael; McElroy, Christopher; Shifflet, Marla; Kasanga, EllaPurpose: The motor deficits of Parkinson's disease (PD): bradykinesia, resting tremors, postural instability and/or rigidity are predominantly unilateral early at diagnosis, progressing bilaterally into moderate stages of the disease. In rats, unilateral impairment can be generated using the neurotoxin 6-hydroxydopamine (6-OHDA). Progression of these deficits can be evaluated to provide insight into gradual bilateral impairment and resulting neuropathological changes. This study employed two locomotor function assays: the forepaw adjusting steps (FAS), which is an 'imposed-movement' test and the open-field locomotor (OFL) test, which relies on "at-will' movement, to longitudinally evaluate bradykinesia and impact of an FDA-approved antibiotic, initiated after lesion induction, as a potential repurposed drug in a 6-OHDA model. Method: 3-month old male Sprague-Dawley rats were evaluated at four time-points after lesion induction (days 7, 14, 21 and 28). Results: The OFL tests did not reveal any significant change in activity although there was a trend towards a decrease in ambulatory counts in the lesioned group over the 4-week period. However, FAS revealed a sustained deficit in right forepaw use (~50 %) while a compensatory increase in the use of the unaffected (left) forepaw was observed. The antibiotic further increased left forepaw use although no significant improvement was seen with the OFL test. Conclusion: Lesioning of the nigrostriatal pathway led to a transient compensatory increase in left forepaw use, an effect which was sustained by antibiotic administration suggesting a benefit that may curtail the onset of bilateral impairment.