Abstract:
To improve the outcome after autologous nerve grafting in the clinic, it is important
to understand the limiting variables such as distinct phenotypes of motor and
sensory Schwann cells. This study investigated the properties of phenotypically
different autografts in a 6 mm femoral nerve defect model in the rat, where the
respective femoral branches distally of the inguinal bifurcation served as homotopic,
or heterotopic autografts. Axonal regeneration and target reinnervation was analyzed
by gait analysis, electrophysiology, and wet muscle mass analysis. We evaluated
regeneration-associated gene expression between 5 days and 10 weeks after repair,
in the autografts as well as the proximal, and distal segments of the femoral nerve
using qRT-PCR. Furthermore we investigated expression patterns of phenotypically pure
ventral and dorsal roots. We identified highly significant differences in gene expression of
a variety of regeneration-associated genes along the central – peripheral axis in healthy
femoral nerves. Phenotypically mismatched grafting resulted in altered spatiotemporal
expression of neurotrophic factor BDNF, GDNF receptor GFRα1, cell adhesion
molecules Cadm3, Cadm4, L1CAM, and proliferation associated Ki67. Although
significantly higher quadriceps muscle mass following homotopic nerve grafting was
measured, we did not observe differences in gait analysis, and electrophysiological
parameters between treatment paradigms. Our study provides evidence for phenotypic
commitment of autologous nerve grafts after injury and gives a conclusive overview
of temporal expression of several important regeneration-associated genes after repair
with sensory or motor graft.
