Stroke is the leading cause of disability in the United States. The long-term objective of our research is to advance the recovery of functional mobility following stroke to reduce post-stroke disability. After stroke, individuals must learn or relearn movements that have been disrupted due to damage to the brain. Neuroplasticity is the mechanism by which the brain learns behavior and neuroplasticity and learning can occur after stroke. Yet, the literature provides little information about the process of relearning movements or the mechanisms that facilitate or impede this learning after stroke. In particular, very little s known about the process of relearning to walk following stroke, even though recovery of walking is often the primary goal of stroke survivors. A lack of understanding of the factors that contribute to slowed learning, or that can facilitate improved learning, hamper our ability to design optimal rehabilitation interventions. We propose that recent developments in our understanding of the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity and motor learning may be capitalized on to address this gap. BDNF has long been known to be a mediating factor in cortical plasticity and motor learning, making it a logical target for the stud of the brain-behavior relationships that underlie post-stroke motor learning. Neurologically intact humans with a common single-nucleotide polymorphism in the BDNF gene code (Val66Met) that affects activity-dependent BDNF secretion, show deficits in motor learning and persons with stroke and the polymorphism show poorer initial recovery from stroke.
Aim 1 of this proposal will determine the impact of the BDNF Val66Met polymorphism on learning a novel walking task after stroke and as such, will identify a potential biomarker that could be used to individualize post-stroke rehabilitation. In contrast, increases in the release of the activity-dependent mature form of BDNF, facilitated by a single bout of high intensity aerobic exercise enhances cognitive and motor learning in neurologically intact humans.
Aim 2 of this proposal will determine the effect of a single, short bout of intense exercise on learning a novel walking task after stroke. Because the high intensity exercise bout is hypothesized to improve motor learning through a BDNF mediated mechanism, it is possible that any effect of the exercise will be attenuated in subjects with the polymorphism. We will therefore examine the effect of the BDNF Val66Met polymorphism on the results in this Aim. The knowledge gained from the studies in this proposal will provide exciting new information that can be used in the development of innovative rehabilitation interventions that promote neuroplasticity to improve recovery after stroke.

Public Health Relevance

After stroke, individuals must learn or relearn movements that have been disrupted due to damage to the brain. Yet, previous research provides limited information about the process of relearning to walk after stroke. This proposal will examine the brain-behavior relationships that underlie learning to walk after stroke.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD078330-01A1
Application #
8816480
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Michel, Mary E
Project Start
2014-09-22
Project End
2018-05-31
Budget Start
2014-09-22
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$194,220
Indirect Cost
$69,720
Name
University of Delaware
Department
Other Health Professions
Type
Schools of Allied Health Profes
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716