Chronic testosterone deprivation sensitizes the middle-aged rat brain to damaging effects of testosterone replacement




Vann, Philip
Smith, Charity
Wong, Jessica
Sumien, Nathalie
Cunningham, Rebecca
Metzger, Daniel
Schreihofer, Derek
Oppong-Gyebi, Anthony
Contreras Garza, Jo
Kasanga, Ella


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Hypothesis: 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.