An electrophysiological and histological study of trypsin induced demyelination.

Ten-microliters quantities of trypsin or saline were injected into rat tibial nerve and the physiological and histological changes evaluated and compared to the focal demyelinating lesions induced by intraneural injection of rabbit EAN serum and proteinase K. The injection of trypsin produced progressive conduction block that was maximal on day 4, and a slowing of motor nerve conduction. Early retraction of myelin at paranodes, vesicular change, and macrophage stripping of myelin from nerve axons were seen on histological examination. At day 4, the first groups of completely demyelinated axons were seen, typically in a perivascular distribution. These changes were similar to those seen in the positive controls and thus support the postulate that proteolytic enzymes from macrophages--the dominant cellular species within the demyelinating lesion, play a central role in degradation of the myelin sheath in demyelinating diseases.