End-to-side neurorrhaphy is indicated when a proximal nerve stump is unavailable due
to trauma, surgical resection, or disease. A growing body of literature supports the
use of end-to-side nerve repairs for the treatment of peripheral nerve injuries. However,
the key determinants of functional outcome remain largely unknown. It was hypothesized
that donor nerve injury and younger age would both favor enhanced nerve regeneration.
The reported experiment tested these hypotheses across a spectrum of donor nerve injury
and animal age.
Twenty-eight rats were randomized to four end-to-side experimental groups that corresponded
to progressively greater donor nerve injury: 1) donor nerve with perineurial window
alone; 2) donor nerve with crush; 3) donor nerve with partial neurotomy; and 4) complete
nerve transection. In this experiment, the terminal limb of a transected peroneal
nerve was sutured to the lateral aspect of a tibial nerve. Animals were then allowed
to regenerate for 12 weeks. Seventy-two hours prior to harvest, peroneal nerves were
injected with the retrograde tracers fast blue and fluorogold. Spinal cords, peripheral
nerves, and extensor digitorum longus muscles were harvested. Motor neuron cell body
counts and peripheral nerve regeneration were quantified by fluorescence microscopy
and histomorphometry. Normalized set muscle masses were determined for functional
assessment. Physiological and ultrastructural features of the perineurial window were
also characterized. The effect of age on neuroregenerative capacity was investigated
by analysis of separate animal cohorts reconstructed at ages 2 weeks, 3 months, and
1 year.
More severe donor nerve injury was strongly associated with increased motor neuron
counts, enhanced peripheral nerve regeneration, and progressive increase in normalized
wet muscle mass (p < 0.05). A significant age-related effect on regeneration was noted,
with improved regeneration in younger animals (p < 0.05). Detailed analysis of the
perineurial window demonstrated significant compromise of blood-nerve barrier integrity
and ultrastructural evidence of demyelination and axonal injury.
The benefits of end-to-side neurorrhaphy will be realized only if motor neuron regeneration
is sufficiently robust to support meaningful functional recovery. The data demonstrated
that nerve regeneration across end-to-side repair is a function of donor nerve axotomy.
Surgical transection of donor axons at the time of end-to-side nerve reconstruction
is therefore a potent stimulus for regeneration and may optimize functional outcomes.
The perineurial window is a measurable, albeit inadequate, donor nerve injury. This
finding calls into question the efficacy of “noninjury” approaches to end-to-side
reconstruction. Finally, regeneration may be more successful in younger subjects.
