Neuromuscular Recovery using Calcium Protease Inhibition after Median Nerve Repair in Primates

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-08, Vol.86 (15), p.5983-5987
• Main Authors: Badalamente, Marie A., Hurst, Lawrence C., Stracher, Alfred
• Format: Article
• Language: English
• Subjects: Animal morphology; Animals; Antibodies; Axons; Biological and medical sciences; Biopsies; Calpain - antagonists & inhibitors; Cebus; Cebus apella; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Immunocytochemistry; Leupeptins - pharmacology; Median nerve; Median Nerve - drug effects; Median Nerve - physiology; Motor Neurons - drug effects; Motor Neurons - physiology; Muscles; Nerve Regeneration - drug effects; Nerves; Neural Conduction - drug effects; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Oligopeptides - pharmacology; Peripheral nerves; Primates; Striated muscle. Tendons; Time Factors; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.15.5983

Inhibition of calcium-activated neutral protease, in muscle and nerve, by the tripeptide leupeptin after median nerve transection and epineural repair in monkeys (Cebus apella) was studied. Results indicate that inhibition of the protease after nerve repair facilitates morphologic recovery in denervated thenar muscles and in distal thenar nerve branches. In addition, functional recovery was facilitated in leupeptin-treated animals after nerve repair as measured by sensory and motor conduction velocities. Toxicologic testing showed that leupeptin, administered at 18 mg/kg, intramuscularly, twice daily, for 6 months did not adversely affect hematology, clotting, or plasma complement component C3 profiles. These data indicate that leupeptin is an effective and safe adjunct to peripheral nerve repair.