The Impact Of Systemic Estradiol Modifications On Ventilation And Respiratory Neuroplasticity
2023-08
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The Impact Of Systemic Estradiol Modifications On Ventilation And Respiratory Neuroplasticity
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2023-08
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Respiratory neuroplasticity is the brain’s ability to adapt in response to stimuli within the respiratory neural network. One of the ways to induce respiratory neuroplasticity is through intermittent hypoxia, which are episodic periods of low oxygen. These hypoxic episodes cause an increase in neural drive, and a subsequent increase in breathing frequency and depth of breath that can result in long term changes in the output of the respiratory network. Two forms of respiratory plasticity that we study are phrenic long-term facilitation (pLTF) and ventilatory long-term facilitation or vLTF. Both forms of plasticity are induced by intermittent hypoxia and are defined as a sustained increase in neural output to the phrenic nerve (pLTF) or sustained increase in minute ventilation (vLTF) following intermittent hypoxia. Estrogen is a known neuromodulator that is found to be influential in the induction for both forms of plasticity. The goal of this research was to examine how altered circulating estrogen would change the respiratory system and the induction of respiratory neuroplasticity. This was explored in three unique ways. We first explored whether endogenous estrogen recovery through extra-gonadal sites of production following removal of the ovaries in female rats could facilitate respiratory neuroplasticity. In a second model, we explored exogenous dosing of sex hormones, including estrogen, following cervical spinal cord injury, an injury causing sustained reductions in circulating hormones. Our goal was to restore conditions for respiratory plasticity in a sub-acute period of recovery. Finally, we looked at a third model, the Total Western Diet, which is reported in humans to increase estrogen in males and females. Overall, our findings were consistent with the idea that estrogen is an important modulator of breathing function and the expression of respiratory neuroplasticity. We determined that estrogen created from sites other than the ovaries was not sufficient to restore plasticity in 3 months’ time following removal of the ovaries. In the second model, both estrogen and testosterone were able to restore respiratory neuroplasticity following an acute spinal cord injury, a novel finding. In the third model, the Total Western Diet appeared to abolish respiratory plasticity, which was a surprising result. Throughout all of these models, a secondary side effect likely included some amount of systemic inflammation. Estrogen is known to have anti-inflammatory properties. The next steps of this research is to look at the interaction of estrogen and inflammation and their influences on respiratory neuroplasticity. With this knowledge we may be able to bypass the inhibitory impact of inflammation that results with reduced levels of estrogen, or with certain dietary changes, and induce respiratory plasticity once again in a way which could be helpful in the therapeutic setting for those with difficulty breathing.
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University of Minnesota Ph.D. dissertation. August 2023. Major: Rehabilitation Science. Advisor: Brendan Dougherty. 1 computer file (PDF); viii, 159 pages.
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Barok, Rebecca. (2023). The Impact Of Systemic Estradiol Modifications On Ventilation And Respiratory Neuroplasticity. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/258883.
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