Stroke leads to profound physical deconditioning and abnormalities in paretic leg muscle including shift to fast twitch muscle phenotype, inflammation and gross atrophy that worsen cardiometabolic health by promoting insulin resistance. Yet, no prior studies have considered stroke as a catabolic syndrome in aging that can be modified by early exercise to improve muscle and cardiometabolic health. In chronic stroke, we have exercise models that improve mobility, restore fitness levels nearly 40%, and reverse impaired glucose tolerance (IGT) and T2DM status in 58% of cases, even years after stroke. Lab findings suggest our exercise programs increase total myofibrillar protein and proportion of slow twitch in paretic leg muscle, implicating both altered protein synthesis and regulation of muscle molecular phenotype as mechanisms underlying the benefits of exercise post-stroke. This study investigates the hypothesis that in African-Jamaican adults with recent stroke, structured exercise across the sub-acute recovery period and into the chronic phase of stroke care will improve P leg muscle and cardiometabolic health, compared to controls receiving best medical care.
Aims and associated hypotheses are to compare effects of 6 months structured and progressive exercise vs. best medical care implemented early after stroke in African-Jamaican adults on:
Aim #1. Paretic &non-paretic leg mixed muscle protein synthesis and breakdown in the fed and fasted state, TNF-1 expression, thigh muscle volume and strength. Hypothesis 1: Paretic leg muscle has reduced protein synthesis and increased breakdown compared to non- paretic leg;Exercise will increase mixed muscle protein synthesis and reduce breakdown to increase muscle volume and strength by mechanism(s) of reducing inflammation in paretic leg, compared to controls.
Aim #2. Glucose tolerance, fitness, and muscle phenotype. Hypothesis 2: Exercise will improve fitness levels, insulin and glucose response to oral glucose challenge, and increase paretic leg slow twitch muscle phenotype.

Public Health Relevance

Chronic hemiparetic stroke is associated changes in body composition, skeletal muscle and cardiometabolic health;specific changes include paretic limb muscular atrophy, increased intramuscular fat deposition, elevated prevalence of impaired glucose tolerance and type 2 diabetes. This randomized intervention study compares a 6 month task oriented exercise programs versus control with both groups receiving best medical stroke care according to American Stroke Association Get with the Guidelines. The hypothesis is that is 6 months of task-oriented exercise initiated early across the sub-acute period of stroke can prevent or ameliorate the natural course of these body composition, skeletal muscle and cardiometabolic health changes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD068712-04
Application #
8606485
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Shinowara, Nancy
Project Start
2011-04-01
Project End
2016-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
4
Fiscal Year
2014
Total Cost
$413,290
Indirect Cost
$30,073
Name
University of Maryland Baltimore
Department
Neurology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201