Structural and functional studies on nerve regeneration in the rat

Sammanfattning: Peripheral nerves cannot be repaired, but they may be helped to regenerate. The results of surgical treatment of nerve injuries remain disappointing, however. This is a biological rather than a technical challenge. An eventual future achievement of improved results with respect to nerve regeneration demands a better knowledge of the basic biological processes and how to manipulate them.The main aim of the present work was to generate knowledge on nerve regeneration, which may be relevant for the understanding of nerve injuries affecting the human hand and for the treatment of these conditions.Electron microscopic (EM) analysis of the occurrence of myelinated and unmyelinated axons shows that regeneration is not the same in articular, cutaneous and muscular branches after crush lesions of the mixed rat sciatic nerve or alter neurotomy and suturing. Each branch presents its own specific pattern. In some respects the abnormalities are larger alter the relatively mild crush lesion than after neurotomy. For example, theoccurrence of both sympathetic and sensory C-fibers increases dramaticallyin the articular branch following sciatic crush lesions (but not alter neurotomy), as judged from observations in chemically sympathectomized animals. Hence, the structural postregenerative pattern in one targetspecific nerve or nerve branch cannot be extrapolated from observations on mixed nerves or 8erve branches to other targets.EM examination of the normal fiber composition of the foot branch of the superficial peroneal nerve (fSPN) and the lateral plantar nerve (LPN) in the rat revealed that the LPN contains a higher proportion of myelinated axons than the fSPN. Some 25% of the myelinated LPN-axons are motor efferents, but the fSPN lacks such axons. Both nerves show about 60% fewer C-fibers after neonatal capsaicin treatment. Neither nerve contains postganglionic adrenergic sympathetic efferents at the level of the ankle. This data form a basis for experimental studies.Three months after crush lesions to the rat sciatic nerve the LPN exhibits elevated numbers of myelinated and unmyelinated axons. In the fSPN the number of myelinated axons is normal and there are fewer C-fibers. Following sciatic neurotomy and suturing the LPN exhibits a more markedly increased number of myeHnated axons and a less markedly decreased number of C-fibers. In the fSPN the number of myelinated axons is increased and the number of C-fibers is slightly decreased. This data show that the outcome of regeneration is different in the LPN and the fSPN after sciatic nerve lesions. The picture in the fSPN is similar to that seen in other nerves to hairy skin.Following rat sciatic nerve lesions the regeneration of functionalpolymodal nociceptors (PMNs; as revealed by stimulation-induced Evans blue extravasation) and low threshold mechanoreceptors (L TMs; as revealed by mild mechanical stimulation) is less efficient in LPN-related glabrous skin than in fSPN- or sural nerve-(SN) related hairy skin. In all three cutaneous domains the regeneration of functional PMNs is more complete than the regeneration of functional L TMs. Thus, this experimental model mirrors the clinical experience that some modalities recover better than others after injuries involving hand nerves. Interestingly, the spatial distribution of functional PMNs is also affected on the contralateral, unlesioned side. Therefore, the contralateral side cannot be used as a normal control in extravasation experiments.A comparison between axon counts and functional evaluations reveals that the number of regenerated axons in a nerve trunk does not reflect the extent of functional recovery.Following repair of divided rat sciatic nerves with fibrin glue (TisseeiDuo ®) the outcome of regeneration in the SN and the LPN differs from the outcome after repair with microsutures with respect to axon numbers, but not with respect to the spatial distribution of functional PMNs and L TMs. Hence, from a functional point of view repair of divided nerves with fibrin glue gives results similar to those seen after suturing.