The Effects of Stroke-Induced Gut Disruption on Acute and Chronic Stroke Recovery: Impact of Sex, Age and IGF1 Treatment

Abstract

Stroke is the leading cause of long-term disability and the fifth leading cause of death in the United States. There are well established sex differences in stroke with young adult males having a worse stroke outcome than young adult females. This paradigm shifts when the aging demographic is considered as at mid-life, women’s stroke risk meets that of men’s and then later exceeds it. The gut is an emerging niche in the field of stroke, and it has been shown to be an early responder to stroke and an influencer of stroke outcome. To determine if worse stroke outcomes correspond to a more severe gut response, I examined the young adult demographic using normally cycling 5–7-month-old female Sprague Dawley rats and age-matched males. In addition to the physical impact of stroke on survivors, there is also an impact on cognition. More than half of stroke patients will suffer from some level of cognitive impairment by 6 months after the stroke event. Post-menopausal women have a higher risk for stroke and a more severe stroke outcome than their male counterparts. Although hypothetically beneficial, hormone replacement therapy worsens their outcome. Post-menopausal women are also more likely to suffer from post stroke cognitive impairment and more likely to need assisted living post stroke. With the limited success on developing stroke therapeutics, shifting focus to a target organ other than the brain may yield more success. The gut is a good candidate as it is shown to respond to stroke and plays a role in inflammation, which is known to worsen stroke outcome and modulate cognitive deficit. In this study, I also determined whether systemic administration of a therapeutic drug would ameliorate the post-stroke gut response and long-term consequences in reproductively senescent 9–11-month-old female Sprague Dawley rats. Overall, this dissertation focuses on examining the gut response to stroke and the gut’s potential as a therapeutic target.