The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury

Abstract

Substantial residual neurological function may persist after spinal cord injury (SCI) with survival of as few as 5–10% of the original number of axons. A detailed understanding of the relationships among the severity of injury, the number and origin of surviving axons at the injury site, and the extent of neurological recovery after SCI is of importance in understanding the pathophysiology of SCI and in designing treatment strategies. In the present study, these relationships were examined in rats with graded severity of clip compression injury of the cord at T1. The rats were randomly assigned to one of the following injury groups ( n = 5 each): normal (laminectomy only), 2-, 18-, 30-, 50-, and 98-g clip injuries. Neurological function was assessed by the inclined plane method and by the modified Tarlov technique. A morphometric assessment of axons at the injury site was performed by a computer-assisted line sampling technique. The origin of descending lions at the injury site was determined by retrograde labeling with horseradish peroxidase. The inclined plane scores varied as a negative linear function of the closing force of the clip used to inflict SCI( r = −0.93; P < 0.0001). The mean axon count was 367,000 ± 529,000 in normal rats and decreased as a negative exponential function of injury force ( r = −0.92; P < 0.0001). As well, SCI caused preferential destruction of large axons as reflected by the change in mean axon diameter from 1.74 ± 0.06 μm in normal cords to 1.46 ± 0.04 μm in injured cords (pooled mean for all injuries). Inclined plane scores varied logarithmically with the number of axons at the injury site ( r = 0.90; P < 0.001) and were highly correlated with the integrity of nonpyramidal tracts, in particular the rubrospinal ( R = 0.89), Vestibulospinal (r = 0.87), and raphespinal ( R = 0.84) tracts. These data demonstrate a precise relationship between the number of surviving axons at the injury site and residual neurological function and confirm the importance of nonpyramidal tracts in modulating gross motor performance.