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LACK OF TOPOGRAPHIC SPECIFICITY IN NERVE FIBER REGENERATION OF RAT FORELIMB MIXED NERVES



Abstract

Aims: Multiple nerve repair by means of a Y-shaped nerve guide represents a good model for studying the specificity of peripheral nerve fiber regeneration. Here we have employed this model for investigating the specificity of axonal regeneration in mixed nerves of the rat forelimb model. Specificity of nerve regeneration can be defined as the ability of the nerve fibers of a peripheral nerve, after a lesion. Tree types of specificity on nerve regeneration has been postulated: “tissue specificity” (the preferential reinnervation of distal nerve tissue versus other types of tissue), topographic specificity (regenerating nerve fibers are preferentially attracted by analogous distal pathways (e.g. preferential regeneration along tibial nerve pathways by tibial nerve fibers), and end-organ specificity, which is the hypothesis that distal end-organs (muscle vs. sensory targets) specifically attracts the respective (motor vs. sensory) regenerating nerve fibers. Exists no agreement regarding the presence and features of the two last type of specificity.

Methods: The left median and ulnar nerves, in adult female rats, were transected and repaired with a 14-mm Y-shaped conduit. The proximal end of the Y-shaped conduit was sutured to the proximal stump of either the median nerve or the ulnar nerve. Ten months after surgery, rats were tested for functional recovery of each median and ulnar nerve. Quantitative morphology of regenerated myelinated nerve fibers was then carried out by the two-dimensional disector technique.

Results: Results showed that partial recovery of both median and ulnar nerve motor function was regained in all experimental groups. Performance in the grasping test was significantly lower when the ulnar nerve was used as the proximal stump. Ulnar test assessment showed no significant difference between the two Y-shaped repair groups. The number of regenerated nerve fibers was significantly higher in the median nerve irrespectively of the donor nerve, maintaining the same proportion of myelinated fibers between the two nerves (about 60% median and 40% ulnar). On the other hand, nerve fiber size and myelin thickness were significantly larger in both distal nerves when the median nerve was used as the proximal donor nerve stump. G-ratio and myelin thickness/ axon diameter ratio returned to normal values in all experimental groups.

Conlusions: These results demonstrate that combined Y-shaped-tubulization repair of median and ulnar nerves permits the functional recovery of both nerves, independently from the proximal donor nerve employed, and that tissue, and not topographic, specificity guides nerve fiber regeneration in major forelimb mixed nerves of rats.

The abstracts were prepared by incoming Professor Elena Brach del Prever. Correspondence should be addressed to IORS – President office, Dipartimento di Traumatologia, Ortopedia e Mediciana del Lavoro, Centro Traumatologico Ortopedico - Via Zuretti, 29 I-10135 Torino, Italy.