Sex Differences in Neuromuscular Fatigability Post Stroke

The purpose of this dissertation was to determine sex differences in neuromuscular fatigability (acute, exercise-induced reduction in power) during dynamic exercise post stroke and identify potential mechanisms related to vascular dysfunction. Female stroke survivors have worse motor-related functional outcomes and lower quality of life. Although multifactorial, one overlooked contributor to sex differences post stroke is fatigability. In addition to baseline weakness, stroke survivors have increased fatigability, limiting task endurance. Sex differences in fatigability may in part explain the worse motor-related functional outcomes for female stroke survivors. Studies have shown that older estrogen-deficient females exhibit blunted vasodilatory responses during exercise compared to younger females, but this age-related difference is not observed in males. Collectively, it is plausible that postmenopausal female stroke survivors have greater vascular dysfunction, resulting in greater fatigability than male stroke survivors. In Aim 1, we quantified differences in fatigability (power reduction) during dynamic exercise in stroke survivors compared to neurotypical controls. Stroke survivors were more fatigable than neurotypical controls. Female stroke survivors were more fatigable than male stroke survivors, but neurotypical males and females fatigued similarly. Fatigability in stroke survivors was negatively associated with muscle oxygenation responses but not exercise-induce hyperemia. In Aim 2, we investigated sex differences in fatigability (total contraction number) during ischemic dynamic exercise post stroke. Female stroke survivors were more fatigable than male stroke survivors under ischemia. The total contraction number was positively associated with the increase in neuromuscular activation. In Aim 3, we explored the effects of ischemic conditioning (IC), which enhances vasodilation, on fatigability (power reduction) during dynamic exercise post stroke. After a single session of IC, male and female stroke survivors were less fatigable than after IC-sham. Improvements in fatigability were positively associated with walking speed and endurance. In summary, when there is free muscle perfusion/reperfusion, mechanisms involving micro-vascular dysfunction contributes more to the greater fatigability in female stroke survivors versus male stroke survivors; whereas in conditions where muscle perfusion/reperfusion is limited, mechanisms for sex differences in fatigability post stroke are likely neural in origin. Lastly, IC could serve as a potential intervention to improve task endurance post stroke.