Axon count studies indicate that very few spinal axons (<10%) can support locomotory and sensory function. Recovering and paralyzed animals often do not show significant differences in the numbers and distributions of axons crossing the lesion site. This suggests that factors besides axonal loss are responsible for the differences in recovery. One such factor is dysfunction of the surviving axons. We recently discovered that injured dorsal column axons show not only conduction failure but hyperexcitability, manifested by decreased compound action potential latencies and increased amplitudes. Such abnormal axonal behaviors can be observed at stimulation frequencies of 20-500 Hz. The broad objectives of this study are to characterize impulse conduction of injured axons and to determine the mechanisms of abnormal impulse conduction. We will examine axonal conduction in rat dorsal column axons after graded contusion and compression injuries, using train and randomized double pulse stimuli protocols to quantify refractory period, fatigability, supernormal behavior, and recruitment patterns of axonal responses. Field potentials and single unit recordings will be made. We hypothesize that traumatically demyelinated spinal axons release more K- and are more sensitive to [K+]e changes. This hypothesis will be tested by measuring activity-dependent [K+]e changes with ion-selective microelectrodes and the effects of exogenously administered K+. For comparison with the behavior of traumatically demyelinated axon, we will study axonal conduction in the mutant myelin-deficient rat. Finally, we will investigate Schwann cell remyelination of axons at contusion and compression sites. This project will provide a detailed in vivo examination of axonal dysfunction in spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS010164-21
Application #
3782566
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
1993
Total Cost
Indirect Cost
Name
New York University
Department
Type
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012