Single-Dose Application of CNTF and BDNF Improves Remyelination of Regenerating Nerve Fibers after C7 Ventral Root Avulsion and Replantation

Abstract

Although axonal regeneration has been observed after replantation of avulsed ventral roots (VR) into the spinal cord, the functional outcome of this treatment in terms of motor reinnervation is unsatisfactory. In the present study, effects of single-dose ciliary and/or brain-derived neurotrophic factor (CNTF, BDNF) application on axon regeneration after C7 VR avulsion and replantation in adult rabbits were morphologically assessed by analysis of numbers, calibers, and myelination of axons in replanted VRs. Electromyography (EMG) was carried out to document the time course of de- and reinnervation in individual animals. After 3 weeks, replanted C7 VRs were almost devoid of myelinated axons. At week 8, active EMG-denervation was confirmed in affected muscles, but was less pronounced in neurotrophic factor (NF)-treated animals than in controls. Reinnervation potentials were identified in paraspinal muscles in more NF-treated animals than in controls. After 6 months, the number of myelinated axons in replanted VRs was approximately 45% of that in unlesioned roots in all groups, with small-sized axons constituting the majority of axons. At this time, more NF-treated animals than controls featured reinnervation. Moreover, myelination deficits of regenerated axons in controls were less pronounced in NF-treated animals. Especially in CNTF + BDNF-treated animals, myelination of regenerated axons of specific sizes was significantly increased compared to regenerated controls. In summary, NFs stimulated reinnervation early after the lesion and, for the first time, our morphological data quantitatively indicate positive effects of CNTF + BDNF on remyelination.