American Society for Peripheral Nerve

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Studying the Role of Gap-Length in Preventing Nerve Regeneration Using a Rabbit Sciatic Model
Antonio Merolli, MD FBSE and Joachim Kohn, PhD FBSE, Rutgers - The State University of New Jersey, Piscataway, NJ

Introduction: A lot of research has been done in the rat sciatic nerve model, however this model limits length and diameter of conduits to be tested. On the contrary, in the New Zealand White (NZW) rabbit sciatic nerve model there is space for conduits as long as 50 mm and with diameters that range from 2.5 mm to 3.5 mm, making this model highly translational for Hand Surgery.

Materials and Methods: Sixteen NZW rabbits received a complete sciatic nerve transection. Tyrosine-derived polycarbonate conduits of 3 mm diameter and 24 mm and 44 mm length were implanted. The early stages of repair were studied in 5 sections: 1-transverse proximal stump; 2-transverse regenerated tissue; 3-longitudinal; 4-transverse regenerated tissue; 5-transverse distal stump. End-points were 0.5, 1, 2, 3, 4, 12, 16 weeks. Histological analysis was performed by a double nonfluorescent immunostaining of myelin basic protein (MBP) and choline acetyltransferase (ChAT) (reciprocal nerve staining/RNS). Non-myelinating Schwann cells were immunolabelled by glial fibrillary acidic protein (GFAP).

Results: RNS shows that there is a differential degeneration pattern between the retrograde degeneration in the proximal stump and Wallerian degeneration in the distal stump. A key feature for both is the enlarged diameter of degenerating axons: however, while ChAT is lost in nearly all the distal axonal stumps, it is retained in the majority of proximal axonal stumps. RNS also shows a limited component of ChAT positive regenerating axons that enter the conduit after 4 months.

Conclusions: The study showed that in gaps longer that 20 mm, the distal stump is too far to provide a contingent of Schwann cells able to reach the axonal sprouting in the proximal stump. At the level of proximal stump, axons degenerate until newly re-growing freshly myelinated axons appear at 3 or 4 months. These new axons may progress aligned with the length of the conduit for a limited distance. Regeneration in longer gaps fails because the distance does not allow a timely match between proximal sprouts and distal Schwann cells. Our study, however, suggests an un-expected advantage of longer conduits if used to control or prevent regeneration from a proximal stump of an amputated nerve; sprouts are allowed to degenerate and new axons are not engulfed by fibroblast/myofibroblasts. This may be useful in control or prevention of amputation neuroma.



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