|Studies show that individuals with subacute and chronic stroke in inpatient rehabilitation facilities and living in the community engage in very little physical activity. Furthermore, people post-stroke have been shown to have low aerobic fitness (peak VO2). Lack of physical activity and reduced aerobic fitness in individuals with stroke may affect their ability to ambulate and perform basic activities of daily living (ADLs). Evidence suggests that greater amounts of time spent in bed during inpatient rehabilitation is associated with poorer outcome on the modified Rankin Scale (mRS), a measure of functional independence, at three months post-stroke. However, no studies in the United States have objectively quantified the amount of activity performed in individuals with acute stroke and how sedentary time relates to functional ability at discharge from the hospital. This information is important for clinical practice in understanding how physical activity and exercise influence recovery after stroke. Moreover, in order to gain a more in-depth understanding of the potential benefits of physical activity, aerobic fitness, and exercise, we need to evaluate the response of potential neuroprotective factors after stroke that are influenced by modifiable lifestyle factors, such as aerobic fitness and physical activity. Insulin-like growth factor-1 (IGF-1), a known neuroprotective agent in animal models, may be among the possible growth factors influenced by lifestyle that are vital to recovery. When IGF-1 is administered by intranasal delivery, core stroke lesion size can be reduced up to 94%, while also improving functional status, compared to vehicle controls. In addition, both circulating levels of IGF-1 and IGFBP-3 can be influenced by physical activity and aerobic fitness in healthy individuals. Therefore, research is needed to better characterize physical activity levels and understand the interaction between physical activity levels, aerobic fitness, and IGF-1 response in individuals with acute stroke. The goal of the work undertaken in this dissertation is to quantify physical activity levels and determine the relationship between IGF-1 response, estimated aerobic fitness, and stroke outcomes following an acute stroke in humans. In order to achieve our goal, we first set out to objectively quantify physical activity levels in individuals with acute stroke and examine the relationship between sedentary time during the hospital stay and functional performance at discharge. In Chapter 2, our investigation of 32 individuals showed that individuals with acute stroke spent a large majority of time sedentary during their hospital stay. Sedentary time was positively related to the Physical Performance Test, even when controlling for baseline performance. This suggests that individuals who spent more hospital time sedentary performed worse on functional tasks prior to discharge, regardless of their performance at baseline. These results demonstrate that people recovering from stroke spend most of their hospital stay sedentary. This may have important implications for stroke recovery. Next, because physical activity is directly related to aerobic fitness and previous literature suggests that aerobic fitness is diminished in individuals with subacute and chronic stroke, in Chapter 3 we set out to examine whether estimated pre-stroke peak VO2 was related to function at hospital discharge. Our results suggest that non-exercise estimation of pre-stroke peak VO2 is easily administered within 48 hours of hospital admission in individuals with acute stroke. Analysis of the relationship between estimated pre-stroke peak VO2 and functional performance at discharge revealed no significant relationships when considering the total sample. However, when stratifying the sample by gender, significant relationships were observed in females between estimated pre-stroke peak VO2 and the Fugl-Meyer Assessment of lower extremity motor function. Females with higher aerobic fitness prior to stroke exhibited better motor function of the lower extremities at discharge from the hospital. However, no significant relationships were observed for men. Therefore, estimations of pre-stroke peak VO2 are feasible to use in individuals during the acute hospital setting. The results of this investigation provide important information for future studies for characterizing fitness prior to stroke and how it may relate to objective measures of physical function during stroke recovery and neuroprotective markers such as IGF-1. Further, because current literature suggests that IGF-1 is neuroprotective after stroke and in healthy individuals, IGF-1 levels can be influenced by physical activity and aerobic fitness, in Chapter 4 we set out to examine IGF-1 and its relationship to estimated pre-stroke peak VO2 levels in individuals with acute stroke. The results indicate that in 15 individuals with acute stroke, estimated pre-stroke peak VO2 is significantly related to circulating IGF-1 levels obtained within 72 hours of hospital admission. Individuals with higher than median IGF-1 levels possessed significantly better aerobic fitness prior to their stroke. These results suggest that improving aerobic fitness prior to stroke may be beneficial and provide neuroprotection by increasing baseline IGF-1 levels. Finally, many studies have seen that individuals with high IGF-1 levels soon after stroke have a greater chance at survival and more independence 3 months later. However, these studies may have a limited understanding of IGF-1’s neuroprotective qualities because they do not consider how the response of IGF-1 during the first weeks of stroke is important and only use general questionnaires to assess outcomes. Therefore, Chapter 5 aimed to characterize the response of IGF-1 during the first week of stroke and how it may be related to outcomes (i.e. discharge placement and independence). Individuals with decreases in IGF-1 levels during the first week of stroke had more desirable outcomes compared to individuals with increases in IGF-1 levels. Individuals with increases in IGF-1 levels and IGF-1 ratio (defined as IGF-1:IGFBP-3) during the first week had a longer length of stay in the hospital, had less independence and greater stroke severity at one month post-stroke, and went to inpatient facilities instead of directly home when discharged from the hospital. Baseline IGF-1 levels and IGF-1 ratio were not related to any outcomes and were not significantly different between those who went home or those who went to inpatient facilities. While other studies have shown that high baseline levels of IGF-1 are related to positive outcomes, our results may provide preliminary evidence that the change in IGF-1 levels and IGF-1 ratio during the first week of stroke are also important to recovery. Further work should be done to investigate the relationship between change in IGF-1 levels early after stroke and functional recovery. In conclusion, this body of work describes physical activity and sedentary levels of individuals with acute stroke while they are in the hospital and how activity relates to functional status at discharge. Further, discussion of using non-exercise peak VO2 in the hospital setting determined that predictive measures of aerobic fitness are practical and easy to use and may potentially have a relationship to both functional recovery and neuroprotection. Our results showed that individuals with acute stroke who have higher pre-stroke fitness levels have higher levels of IGF-1 compared to individuals with acute stroke with lower pre-stroke fitness levels. Finally, this collection of studies revealed that decreases in IGF-1 levels are related to positive short-term outcome during stroke recovery. This is the first investigation of how the response of IGF-1 during the first week post-stroke relates to outcomes and warrants future research. The presented work is novel and significant in that it provides objective measures of activity and neuroprotection very early after stroke and new evidence for the use of easy-to-administer assessments of fitness. These studies set important groundwork for additional research to provide greater detail accounts of the interaction of fitness, physical activity, IGF-1 levels, and functional recovery.