Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy

Abstract

Previously, we have shown that transplants of olfactory bulb ensheathing cells promoted regeneration of transected dorsal roots into the spinal cord. In this study, we assessed the ability of regenerating axons to make functional connections in the cord. Dorsal roots L3 to L6 were sectioned close to their entrance into the spinal cord and reapposed after injecting a suspension of ensheathing cells into each dorsal root entry zone (Group G). Afferent regeneration into the cord and recovery of spinal reflexes were compared with animals that received no injection (Group S) or culture medium without cells (Group C). Electrophysiological tests, to measure nerve conduction and spinal reflexes (H response and withdrawal reflex) evoked by stimulation of afferents of the sciatic nerve, were performed. At 14 days after surgery, H response was found in only 1 of 7 rats of Group G, and withdrawal reflexes were absent from all animals. At 60 days, the H response reappeared in 7 of 10 rats of Group G, and 1 of 5 of each of Groups C and S. The withdrawal reflex recovered in 4 of 10 rats of Group G, but in none of Groups C and S. Immunohistochemical labeling for calcitonin gene-related peptide (CGRP) in rats of Group G showed immunoreactive fibers entering the dorsal horn from sectioned roots, although at lower density than in the contralateral side. In conclusion, transplanted ensheathing cells promoted central regeneration and functional reconnection of regenerating sensory afferents.