Proteinase induced demyelination. An electrophysiological and histological study

The physiological and histological changes following injection of 10 microliter of proteinase K into the rat tibial nerve have been compared with those induced by proteinase K and specific inhibitor phenylmethylsulphonyl fluoride (PMSF) and also by rabbit experimental allergic neuritis (EAN) serum. Proteinase K and PMSF produced no significant change. Proteinase K alone resulted in progressive conduction block which was complete by about 8 h, and a slowing of motor conduction across the injection site. These changes were very similar to those induced by EAN serum. Histological examination showed early intramyelinic oedema and swelling of Schwann cell cytoplasm, followed by vesicular degeneration of myelin and removal by macrophages. At day 6 the demyelination was most prominent in a perivascular distribution. These changes share many similar features to those seen in EAN and are consistent with the postulate that the final common pathway for myelin destruction in the demyelinating diseases involves proteinases released by macrophages.