The long-range goals of this project are to examine the neural mechanisms contributing to functional motor recovery following stroke. These studies will use behavioral training, neurophysiological, neuroanatomical, angioarchitectural, cellular and molecular techniques to examine functional and structural plasticity in motor cortex after an ischemic infarct, and the effects of rehabilitative training on the extent of plasticity and functional motor recovery. To determine whether training modulates the functional organization of motor regions remote from the site of injury, the ventral premotor cortex (PMv) will be used as a model to examine functional topography before, and a few months after an infarct in primary motor cortex. Animals undergoing post-infarct rehabilitative training will be compared with spontaneously recovering animals. Other studies will explore the necessity of the reorganized tissue in supporting the recovered motor abilities. To determine whether alterations in intracortical connectivity occur after an ischemic infarct, neuroanatomical tract-tracing techniques will be used to examine the connectional patterns of the reorganized PMv with other cortical regions. To shed light on molecular mechanisms underlying functional plasticity in PMv, microarray technology will be employed to examine regulation of neurotransmitter systems and the expression of neurotrophins in early and late phases after ischemic injury. To determine the extent of vascular changes in remote areas, markers for angiogenesis will be examined and angioarchitecural techniques will be used to quantify alterations in vascular anatomy in PMv. Finally, the role of the intact (contralesional) primary motor cortex in recovery will be examined. These studies have strong clinical relevance for understanding motor recovery in the acute as well as chronic stages after stroke, and the role of physical rehabilitation in recovery. The correlation of neural and vascular events with motor recovery after stroke may eventually lead to innovative approaches to rehabilitative therapy. It is hoped that eventually, therapeutic techniques for improving recovery of function after stroke will be based on the rules underlying plastic mechanisms in the central nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS030853-10
Application #
6471498
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (01))
Program Officer
Michel, Mary E
Project Start
1993-06-01
Project End
2007-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
10
Fiscal Year
2002
Total Cost
$506,871
Indirect Cost
Name
University of Kansas
Department
Physiology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Plautz, Erik J; Barbay, Scott; Frost, Shawn B et al. (2016) Effects of Subdural Monopolar Cortical Stimulation Paired With Rehabilitative Training on Behavioral and Neurophysiological Recovery After Cortical Ischemic Stroke in Adult Squirrel Monkeys. Neurorehabil Neural Repair 30:159-72
Andrews, Brian T; Lydick, Anna; Barbay, Scott et al. (2016) Reversibility of Murine Motor Deficits Following Hemi-Craniectomy and Cranioplasty. J Craniofac Surg 27:1875-1878
Nishibe, Mariko; Urban 3rd, Edward T R; Barbay, Scott et al. (2015) Rehabilitative training promotes rapid motor recovery but delayed motor map reorganization in a rat cortical ischemic infarct model. Neurorehabil Neural Repair 29:472-82
Murphy, Maxwell D; Guggenmos, David J; Bundy, David T et al. (2015) Current Challenges Facing the Translation of Brain Computer Interfaces from Preclinical Trials to Use in Human Patients. Front Cell Neurosci 9:497
Darling, Warren G; Morecraft, Robert J; Rotella, Diane L et al. (2014) Recovery of precision grasping after motor cortex lesion does not require forced use of the impaired hand in Macaca mulatta. Exp Brain Res 232:3929-38
Barbay, Scott; Guggenmos, David J; Nishibe, Mariko et al. (2013) Motor representations in the intact hemisphere of the rat are reduced after repetitive training of the impaired forelimb. Neurorehabil Neural Repair 27:381-4
Milliken, Garrett W; Plautz, Erik J; Nudo, Randolph J (2013) Distal forelimb representations in primary motor cortex are redistributed after forelimb restriction: a longitudinal study in adult squirrel monkeys. J Neurophysiol 109:1268-82
Dancause, Numa; Nudo, Randolph J (2011) Shaping plasticity to enhance recovery after injury. Prog Brain Res 192:273-95
Nishibe, Mariko; Barbay, Scott; Guggenmos, David et al. (2010) Reorganization of motor cortex after controlled cortical impact in rats and implications for functional recovery. J Neurotrauma 27:2221-32
Guggenmos, David J; Barbay, Scott; Bethel-Brown, Crystal et al. (2009) Effects of tongue force training on orolingual motor cortical representation. Behav Brain Res 201:229-32

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