Suppression of neurofilament degradation by protease inhibitors in experimental spinal cord injury.
Intraperitoneal administration of the neutral protease inhibitors leupeptin and E-64c substantially suppressed the degradation of neurofilament proteins (NFP) at the site of mechanical insult and secondary axonal degeneration, and facilitated the recovery of motor functions in acute spinal cord injury in rats. The drug effects were assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis of NFP fractions from the injured tissue and by morphometry of degenerating axons revealed by the Fink-Heimer method in distal spinal cord segments with the aid of an automated image analyzer. The role of calcium-activated neutral proteases in acute central nervous tissue damage and potential use of protease inhibitors as therapeutic modalities are discussed.
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007976:Leupeptins / Q000627:therapeutic use*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D016900:Neurofilament Proteins; D009842:Oligopeptides / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000032:analysis / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism
D007381:Intermediate Filament Proteins; D007976:Leupeptins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D009842:Oligopeptides; D011480:Protease Inhibitors; D007930:Leucine; C032854:leupeptin; C024974:E 64