The interaction between neural and musculoskeletal systems enables us to perform a variety of motor tasks, such as locomotion, in a robust and adaptable manner. Damage to one system component, e.g. traumatic spinal cord injury, can lead to long-term secondary changes in other system components due to their close interactions and their inherent plasticity. In some instances, these secondary changes may be maladaptive, and therefore result in further reduction in functional capacity; in other instances, the changes may be favorable, and therefore result in recovery of function. In this work, a series of experimental studies in uninjured and incomplete spinal cord inured (iSCI) rodents will drive the development of a detailed mathematical model of the biomechanics and neural control of the rodent hindlimb. This model will be used to investigate the role of complex interactions amongst impaired central drive, spinal reflexes and musculoskeletal changes after iSCI in the design of appropriate therapy. Specifically, a chronic rodent thoracic contusion spinal cord injury preparation will be used to investigate the intrinsic intracellular electrophysiology of spinal motoneurons and their afferent control and the intrinsic musculoskeletal properties present after iSCl. The experimental data will guide development of a computational model with neural and dynamic musculoskeletal components. Hodgkin-Huxley type neuron representations will be used to model the local spinal neural circuits that include motoneurons, interneurons and afferents involved in specific spinal reflexes. The musculoskeletal model will incorporate experimentally-determined geometrical musculotendon paths, inertial properties, muscle fiber properties, and 3D laser scanned bony surface geometries. The comprehensive model will consequently be used to test hypotheses regarding the roles of specific ionic currents, altered central drive, altered musculoskeletal properties and altered sensory reflex gain on control of limb movement after iSCI. Successful completion of the work will provide novel information that could help guide the development of efficient treatment techniques and appropriate rehabilitative therapies for enhancing functional locomotor recovery and quality of life for some of the 200,000 people currently living with spinal cord injury related mobility, employability and secondary health related limitations in the United States of America.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS054282-03
Application #
7237156
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50))
Program Officer
Liu, Yuan
Project Start
2005-08-15
Project End
2009-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$304,026
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
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