MOLECULAR-BASIS OF INTERACTIONS BETWEEN REGENERATING ADULT-RAT THALAMIC AXONS AND SCHWANN-CELLS IN PERIPHERAL-NERVE GRAFTS .2. TENASCIN-C

Tenascin-C is a developmentally regulated extracellular matrix compone nt. There is evidence that it may be involved in axon growth and regen eration in peripheral nerves. We have used in situ hybridization and i mmunocytochemistry to investigate the association of tenascin-C with c entral nervous system axons regenerating through a peripheral nerve au tograft inserted into the thalamus of adult rats. Between 3 days and 4 weeks after implantation, tenascin-C immunoreactivity was increased i n the grafts, first at the graft/brain interface, then in the endoneur ium of the graft, and finally within the Schwann cell columns of the g raft. By electron microscopy, reaction product was present around coll agen fibrils and basal laminae in the endoneurium, but the heaviest de posits were found at the surface of regenerating thalamic axons within Schwann cell columns. Schwann cell surfaces were not associated with tenascin-C reaction product except where they faced the tenascin-rich basal lamina or were immediately opposite axons surrounded by tenascin -C. By 8 weeks after graft implantation tenascin-C in the endoneurium and around axons of the graft was decreased. In the brain parenchyma a round the proximal part of the graft, axonal sprouts associated with t enascin-C could not be identified earlier than 2 weeks after grafting and were sparse at this stage. Larger numbers of such axons were prese nt at 8-13 weeks after grafting and were located predominantly where t he glia limitans between brain and graft appeared to be incomplete, su ggesting that the tenascin-C may have penetrated the brain parenchyma from the graft. By in situ hybridization, cells expressing tenascin-C mRNA (probably Schwann cells) appeared first at the brain/graft interf ace 3 days after grafting and thereafter were mainly located within th e grafts. Lightly labelled cells containing tenascin-C mRNA (probably glial cells) were scattered in the thalamic parenchyma both ipsilatera l and contralateral to the graft and a few heavily labelled cells were located very close to the tip of the graft. These results show that r egenerating adult thalamic axons, unlike regenerating peripheral axons , become intimately associated with peripheral nerve graft-derived ten ascin-C, suggesting that they express a tenascin-C receptor, as many n eurons do during development, and that tenascin-C derived from Schwann cells may play a role in the regenerative growth of such axons throug h the grafts. (C) 1995 Wiley-Liss, Inc.