Remyelination in the rat dorsal funiculus following demyelination by laser irradiation.

Excimer laser (KrF excimer laser, 248 nm wavelength) was used to damage cellular components in the dorsal funiculus at the lumbar level (L2) of the rat spinal cord. An open lesion was not found at the irradiation site on the spinal cord. However, the cytological examination revealed that cellular components were damaged to the depth of 200-500 microm from the pial surface. The characteristic feature was that at the border of the lesion, many axons remained naked but intact after their myelin sheaths had been completely disintegrated. Such naked axons were subsequently remyelinated by mature or immature glial cells. Mature oligodendrocytes, while retaining their cytoplasmic processes connected with the myelin sheaths of unaffected axons, extended new cytoplasmic processes on nearby naked axons and made new myelin sheaths around them. In contrast, 7 days after the irradiation, numerous immature glial cells appeared in association with naked axons, and some of them were differentiated into oligodendrocytes forming thin myelin sheaths on naked axons. These findings suggest that demyelinated axons can cause the proliferation and probably dedifferentiation of the oligodendrocyte lineage. The use of lasers provides a unique experimental model of demyelination and remyelination in the central nervous system of adult mammals.

Effects of prelesioned peripheral nerve graft on nerve regeneration in the rat spinal cord.

OBJECTIVE: The aim of this study was to examine the effects of prelesioned peripheral nerve grafts on central nerve regeneration compared with the freshly transected peripheral nerve grafts in the dorsal funiculus of the rat spinal cord. METHODS: The experimental paradigm consisted of ligating the common peroneal nerve at the midthigh level for 7 days, while the adjacent tibial nerve was left intact. Numerous Schwann cells appeared accompanying regenerating axons in the proximal stump of the ligated nerve. The proximal stumps of the ligated (prelesioned) common peroneal nerve and the intact (untreated) tibial nerve were excised as one tissue block and autografted into the dorsal funiculi of the upper cervical cord. The graft was placed so that the prelesioned common peroneal nerve was positioned on the left dorsal funiculus and the untreated tibial nerve was positioned to the right of the midsagittal plane. Nerve regeneration was examined by light and transmission electron microscopy 1 to 16 weeks after grafting, comparing the effectiveness of prelesioned and untreated nerve grafts. RESULTS: Numerous regenerating axons were observed in the caudal border of both grafts 1 to 2 weeks after grafting. Astrocyte proliferation was suppressed in the prelesioned grafts compared to the untreated grafts. Four to 16 weeks later, the number of regenerating axons was approximately 10-fold as large in the prelesioned grafts as in the untreated grafts. The regenerating axons were myelinated by Schwann cells. Astrocytic glial scar formation was inconspicuous in the prelesioned grafts, whereas it was prominent in the untreated grafts. Schwann cells were contiguous with astrocytes along regenerating axons, forming a continuous conduit from the central to peripheral nerve microenvironments for the outgrowth of regenerating axons. CONCLUSION: The prelesioned peripheral nerve graft is more effective than the untreated graft in suppressing astrocytic scar formation and in supporting the outgrowth of regenerating axons in the dorsal funiculus of rat spinal cord.