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Epineurial Windows are Necessary for Donor Axons to Regenerate Across an Autograft into Recipient Denervated Rat Nerve Stumps: the Axons Grow Equally in Proximal and Distal Directions
Tessa Gordon, MD1; Adil Ladak, MD, MSc2; Holliday Carter1; Jennifer Zhang, MD1 ; Gregory H. Borschel, MD1
1Plastic Surgery, The Hospital for Sick Children, Toronto, ON, Canada; 2Division of Plastic and Reconstructive Surgery, University of Alberta, Edmonton, AB, Canada
Introduction: 1) Whilst donor axons may cross an end-to-side repair without creating an epineurial window1, epineurial windows may permit more axons to grow into a denervated nerve stump. Would window size affect axon growth across two end-to-side neurorrhaphies (cross-bridges), through an autograft and into a recipient denervated nerve stump? 2) Sprouting of donor axons was reported after end-to-side neurorrhaphy2. What is the relative contribution of sprouting and regeneration of donor nerves into the denervated nerve stump? 3) As donor axons prevent atrophy of denervated Schwann cells and facilitate axon regeneration after delayed nerve repair3, we ask whether these axons grow either side of the bridges in the denervated stumps.
Methods: 1) Common peroneal (CP) autografts, 1-9 in number and either 6 or 3.2mm in length, were secured with Tisseel glue between 10mm lengths of a donor tibial nerve and a recipient CP distal nerve stump. Epineurial windows of ~1.5mm, 2 and 4mm were opened for comparison of tibial nerve growth through 1 and 3 bridges and, in a subset of rats, the CP nerve stump was ligated 20mm distal to the bridges. Motor and sensory neurons were backlabelled with fluorescent dyes 3 months later to count the tibial neurons that had sprouted (contained dye applied both to the tibial donor nerve and the CP nerve stump) and/or regenerated axons proximal and/or distal to the bridges.
Results:1) The numbers of donor tibial neurons that regenerated axons into recipient denervated CP nerve stump increased with the diameter of the epineurial windows: <1%, ~5% and ~34% of the motoneurons regenerated axons through 3 bridges placed between ~1, 2, and 4 mm windows, respectively. 2) Few motor and sensory tibial neurons sprouted axons into the CP stump, the majority regenerating their axons. 3) The same numbers of motor and sensory tibial neurons regenerated axons in the recipient CP nerve stump proximal and distal to the bridges and, the axon numbers were equal on either side irrespective of whether the CP stump was ligated distally. The latter finding eliminated possible retrograde neurotrophism.
Conclusions: Epineurial windows are necessary for donor axons to regenerate across an autograft into a recipient denervated nerve stumps. Axons grow equally in proximal and distal directions. They sustain chronically denervated Schwann cells to improve nerve regeneration3.
References 1. Viterbo F et al Plast Reconstr Surg 124:e351 2009
2. Zhang Z et al Microsurg 19:281 1999
3. Ladak et al Neurosurg 68:1654
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