Repair of divided peripheral nerves : experimental studies in rabbit and rat

• The general aim of this thesis was to provide new knowledge, through experimental studies, that may contribute to an improvement of the results after microsurgical peripheral nerve repair in patients.An adequate function of the human body depends, among other things, on a correctly functioning peripheral nervous system. Peripheral nerve injuries may impair the motor and sensory function of muscles, the proprioceptive joint control, the cutaneous sensibility, and the autonomic control of the skin, which can result in severe dysfunction of e.g. an extremity. The worst grade- of nerve injury is the division of an entire nerve. In the ideal case, the divided nerve can be sutured so that the distal and proximal nerve stumps are brought together. When peripheral nerve tissue has been lost at the site of injury, a direct repair is not possible. In such cases, the use of nerve grafts to bridge the defect, and/or suture of the distal nerve stump to an entirely different donor nerve is necessary to restore some function. Both types of such nerve repair, however, produce new sequelae due to loss of function of the nerves used for repair. To avoid such donor nerve morbidity, two different types of repair, end-to-end coaptation to part of a healthy donor nerve and end-to- side neurorrhaphy were investigated experimentally.Neurotomy studies in the rabbit showed that use of 1/3 of a donor nerve (ulnar nerve) for reinnervation of an agonistic recipient nerve (median nerve) results in a useful muscle function with negligible donor nerve morbidity.In the rat, end-to-side neurorrhaphy of a recipient nerve (median nerve) to an agonistic donor nerve (ulnar nerve) turned out to give a useful muscle function without causing donor nerve morbidity. After end-to-side neurorrhaphy, reinnervation of the recipient nerve stump was executed by collateral sprouting from intact donor nerve axons. The regeneration of sensory axons was numerically superior to the regeneration of motor axons. Altogether, however, good results after end-to-side neurorrhaphy are not predictable.Both types of nerve repair (end-to-side neurorrhaphy and partial end-to-end neurorrhaphy) give better results with respect to reinnervation of a nerve to a simple muscle target than with respect to reinnervation of a nerve to a complex muscle target.In the ideal situation, after conventional end-to-end nerve suture, nerve repair results in an axonal regeneration that restores muscle function as well as cutaneous sensibility and autonomous function. However, a completely normal function is usually not achieved due to e.g. aberrant axonal regeneration that results in a nerve-target mismatch. One of the causes for aberrant regeneration is axonal criss-crossing between fascicles in adjacency. Hence, barriers of different materials were tested in the rat to see if interfascicular axonal criss-crossing can be counteracted.Three materials - a pedicle fat flap, Integra®, and non-vascularized autologous fasciawere used as barriers between the peroneal and the tibial fascicles in rats. The results showed that all three barriers improved axonal alignment after sciatic nerve transection and fascicular end-to-end repair. The pedicle fat flap was the most valuable barrier.Finally, coaptation of the divided rat sciatic nerve with the aid of couplers, normally used for microvascular anastomoses, was evaluated as a method to hinder erratic centrifugal axon growth. The results showed that couplers provided a secluded coaptation site avoiding aberrant axonal sprouting to the surroundings. However, a minor nerve compression was evident.Altogether, these results show that the microsurgical repair of nerve transections can be improved a bit further. However, the future developments in this area are likely to occur at the molecular level.

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MEDICINE

MEDICIN

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