Laminin in traumatized peripheral nerve: Basement membrane changes during degeneration and regeneration

Abstract

The changes in Schwann cell basement membrane associated with degeneration and regeneration during 50 weeks after transection of rat sciatic nerve were studied immunohistochemically with antibodies to laminin. In half of the animals, regeneration was prevented by suturing the nerve stumps aside, whereas in the rest spontaneous regeneration was allowed. Axonal regeneration was monitored with anti-neurofilament protein antibodies. In control nerves, basement membranes surrounding Schwann cells were visualized as circular, laminin-positive structures within the endoneurium. By 8 weeks after transection, Schwann cells had formed columns which were laminin-positive throughout their cross-sectional area and indistinguishable from basement membrane zones in both non-regenerating and regenerating nerves. As axons repopulated the distal stump, the normal shape of Schwann cell basement membrane tubes was slowly restored in freely regenerating nerves. In non-regenerating nerves, however, a striking atrophy of Schwann cell columns was observed. Regenerating axons were only seen inside laminin-positive tubular structures in all phases after 8 weeks in regenerating nerves. On the other hand, restoration of normal shape in laminin-positive basement membrane zones was coincident with appearance of axons in the distal stump, but it did not take place in chronically degenerating nerves. The results show that chronic degeneration leads to an atrophy of Schwann cell columns and results in a decrease in laminin immunoreactivity associated with them.

Extracellular matrix in regenerating rat sciatic nerve: a comparative study on the localization of laminin, hyaluronic acid, and chondroitin sulfate proteoglycans, including versican.

“…In conclusion, this study shows that, in addition to laminin (3,26), proliferating Schwann cells forming the bands of Biingner characteristic of Wallerian degeneration produce other components of normal endoneurium, i.e., hyaluronic acid and CS proteoglycan. The absence of versican, a normal endoneurial constituent, is worth noting in view of the fact that hyaluronate binding proteoglycans inhibit cell migration (24).…”

Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro.

“…The a2/(3 1 integrin receptor complex is thus likely to have a major role in mediating the interactions between Schwann cells and endoneurial connective tissue. Schwann cells are surrounded by a basement membrane composed of laminin, merosin, and type IV collagen (24,50,51). All these components are potential candidate ligand molecules for Schwann cell matrix interaction because the a2/# 1 complex has been shown to function both as collagen and as laminin receptor (8).…”

“…Neural development during embryogenesis or as part of nerve repair is a complex process which apparently involves cell-cell and cell-matrix interactions (17,(20)(21)(22)(23)(24). At least three cell types of neural connective tissue, Schwann cells, perineurial cells, and fibroblasts, are involved in these processes (22,23,25).…”

Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation

“…There are a number of possible explanations for the progressive deterioration in the ability of intramuscular nerve sheaths to support regenerating axons back to long-term denervated muscle fibers. (1) The initial proliferation of Schwann cells is not maintained and the number of Schwann cells may decrease to a level at which adequate substrate and trophic support is no longer available (Weinberg and Spencer, 1978;Pellegrino and Spencer, 1985;Salonen et al, 1985;Salonen et al, 1987). (2) The basal lamina, which cannot be renewed without Schwann cell-axon contact (Bunge et al, 1982), begins to fragment within weeks of denervation (Giannini and Dyck, 1990).…”