Efficient reinnervation of hindlimb muscles by thoracic motor neurons after nerve cross-anastomosis in rats.

Abstract

Peripheral motor axons can regenerate through motor endoneurial tubes of foreign nerves to reinnervate different target muscles. This regenerative capacity has been brought to clinical applications for restorative surgery after nerve or root injury. In this study the authors explore the extent to which nerve cross-anastomosis between lower intercostal nerves and lumbar ventral roots would be effective in inducing reinnervation of paralyzed hindlimb muscles after spinal cord hemisection at the thoracolumbar boundary in rats. The proximal extremities of sectioned intercostal nerves T10-12 were surgically connected to the distal extremities of sectioned ipsilateral lumbar ventral roots L3-5, respectively. Motor activity reappeared 2 months postsurgery; however, locomotion was not restored and inappropriate motor patterns persisted at 9 months postsurgery. At that time, data from electrophysiological and histological studies and horseradish peroxidase retrograde labeling demonstrated efficient regrowth of thoracic motor neuron axons that reached hindlimb muscles. They also revealed a persistent maturation defect of regrown fibers, as shown by size heterogeneity and presumable extensive axonal branching. These features are consistent with reduced neural activity subsequent to continuing inappropriate motor patterns. These results indicate that cross-anastomosis of intercostal nerves with lumbar ventral roots allows efficient reinnervation of paralyzed hindlimb muscles after spinal cord hemisection in rats. Stimulating the reorganization of the neuronal circuitry in the central nervous system by locomotion training or other methods would presumably result in both functional and anatomical improvements. This experimental setting provides a convenient animal model to investigate these processes.