EARLY AXONAL REGENERATION - REPRESSION BY SCHWANN-CELLS AND A PROTEASE

We have proposed that mature Schwann cells and an extracellular protea se repress the sprouting response of axons. To test this hypothesis, w e destroyed all cells by freezing a short span of the rat sciatic nerv e or inhibited proteases with subperineurial injections of aprotinin, and a crush was made to induce the sprouting response. In unconditione d or in vehicle-injected nerves, axons began to elongate at a constant rate after a delay of about 1 day. The freezing of the nerve distal t o the crush obliterated the delay, but the rate of elongation did not change. A similar pattern was observed when the nerve segment was cond itioned with aprotinin for 2 days prior to the crush. These effects we re abolished when a short untreated segment was left between crush and conditioned region of the nerve. The electron microscopy of the nerve and the immunolocalization of the growth-associated protein (GAP-43) were consistent with the enhanced regrowth observed in conditioned ner ves. Our findings support the notion that Schwann cells repress the on set of regeneration and that a local protease is involved. (C) 1995 Ac ademic Press, Inc.