Role of axon-deprived Schwann cells in perineurial regeneration in the ratsciatic nerve

The role of Schwann cells (SC) in perineurial regeneration after nerve inju ry has not yet been resolved. It was hypothesized that SC alone are able to induce at least partial morphological restoration of the destroyed orthoto pic perineureum (PN). To test the hypothesis, a permanently denervated segm ent of the rat sciatic nerve was made acellular by freeze-thawing, except i n its most proximal part where non-neuronal cells were left intact. Restora tion of the frozen segment by these cells was examined by electron microsco py and immunohistochemistry of the SC marker, S-100 protein, 4 and 8 weeks after injury. The PN regenerated from undifferentiated fibroblast-like cell s. In the presence of migrant SC without axons, regenerated cells in the pl ace of the former PN were stacked in several layers and, in accordance with the hypothesis, partially expressed typical features of the perineurial ce lls (PC): pinocytotic vesicles, short fragments of basal lamina and tight j unctions. Migrant SC induced formation of pseudo-minifascicles even in the epineurium. In these, SC organized the adjacent fibroblasts into a multilay ered circular sheath, and induced their partial differentiation towards per ineurial cells. Further experiments demonstrated that regenerating axons ar e required for complete morphological differentiation of the regenerated pe rineurial cells either in the orthotopic PN or in minifascicles.