Medical Student Research Fellowship for Summer 2006

Mentor: Keith Tansey, MD, PhD
Department: Neurology
Room number: L1.232
Mail Code: 8897
Phone number: 88747,80487
E-mail: keith.tansey@utsouthwestern.edu

Project I

Project title: Axonal Sprouting in an Intersegmental Pain Circuit after SCI

Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable): 0971-05-04-1

Project Type (patient-based research, animal-based research, or basic research) animal

Brief Description of Project:
The cutaneous trunci muscle reflex is an intersegmental pain reflex we have studied using electrophysiology and histology in a rat model of spinal cord injury. The cells that make up the reflex are dorsal cutaneus nerve afferents, ascending propriospinal interneurons and the motoneurons of the cutaneous trunci muscle and it is the ascending propriospinal neurons that can be damaged in spinal cord injury. In our model, the reflex above the level of injury remains intact but the reflex elicited from below the injury is diminished in proportion to the amount of spared spinal cord tissue at the level of injury. We are interested in determining if the ascending propriospinal interneuronal pathways that remain after spinal cord injury can be induced to sprout at their targets to reconstruct more normal physiological function despite the fewer connections. We plan to inject chondroitinase in the area of the cutaneous trunci motor nucleus to disrupt the extracellular matrix around the motoneurons to see if that allows for sprouting of the ascending propriospinal interneurons and better connections with their motoneuron targets. Sprouting in propriospinal or dorsal root ganglion neurons below the level of injury will be studied to see if these pain pathways can now activate sympathetic neurons in the spinal cord and serve as a model for autonomic dysreflexia, the phenomenon seen in spinal cord injured patients where painful stimulus below the level of spinal cord injury can trigger blood pressure changes.

Project II

Project title: Motoneuron - Muscle Unit Properties Matching in Peripheral and
Central Nervous System Injury

Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable): 0971-05-03-1

Project Type (patient-based research, animal-based research, or basic research) animal

Brief Description of Project:
The relationships between motoneuron properties (size, input resistance, axonal conduction velocity) and muscle unit properties (force production, metabolic profile and fatigability) have been demonstrated in normal animals. It is unclear if these relationships are maintained after spinal cord injury that removes descending pathways inputs to motoneurons and results in muscle inactivity. It is also not known how those relationships are affected after partial or complete peripheral nerve injury and repair. We have been studying spinal cord injury in a rat model and we propose to activate and record from individual motoneurons and their muscle units below the level of spinal cord injury to determine how motoneuron - muscle unit properties relate. We are also studying two peripheral nerve injury models, one incomplete and one complete. In the incomplete injury model, motoneurons still connected to the muscle sprout to take over denervated muscle fibers and may or may not influence their biology to match the motoneuron's. In the complete injury model, axons are encouraged to re-grow to the muscle through biosynthetic conduits and it is not known in this setting how well motoneuron and muscle unit properties re-align with reinervation.

Previous Research Activities or Publications with Medical Students:
Early Locomotor Recovery after Spinal Cord Injury: Contribution of Spinal vs Supraspinal Neural Circuitry, N. Ortiz, C. Smith, B. Botterman, and K. Tansey, (2006 Medical Student Research Forum winner) - Niko Ortiz, MS0, 2005

Tansey, K., Smith, C., Gerety, P., and Botterman, B., Recovery in an intersegmental spinal reflex after contusion injury in the rat, American Spinal Injury Assoc. Abstr., 2005 (Award Platform Session presentation) - Pat Gerety, MS1, 2004

Adipose Derived Neural Progenitor (ADNP) Cells: A Novel Source for Cell Replacement Therapy in Spinal Cord Injury, M.A. Warren, M.K. McCoy, T.N. Martinez, C.G. Smith, B.R. Botterman, M.G. Tansey, and K.E. Tansey (2005 Medical Student Research Forum winner) - Mary Warren, MS1, 2004

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