title: Inhibition of calpains fails to improve regeneration through a peripheral nerve conduit.
abstract: Intramuscular injection of the calpain inhibitor leupeptin promotes peripheral nerve regeneration in primates (Badalamente et al., 1989 [13]), and direct positive effects of leupeptin on axon outgrowth were observed in vitro (Hausott et al., 2012 [12]). In this study, we applied leupeptin (2mg/ml) directly to collagen-filled nerve conduits in the rat sciatic nerve transection model. Analysis of myelinated axons and retrogradely labeled motoneurons as well as functional 'CatWalk' video analysis did not reveal significant differences between vehicle controls and leupeptin treated animals. Therefore, leupeptin does not improve nerve regeneration via protease inhibition in regrowing axons or in surrounding Schwann cells following a single application to a peripheral nerve conduit suggesting indirect effects on motor endplate integrity if applied systemically.
authors.affiliation: Austrian Cluster of Tissue Regeneration and Ludwig Boltzmann Institute for Experimental and Clinical Traumatology at the Research Centre for Traumatology of the Austrian Workers' Compensation Board (AUVA), Donaueschingenstr. 13, 1200 Vienna, Austria; Department of Trauma Surgery and Sports Traumatology, Paracelsus Medical University, Müllner Hauptstr. 48-50, 5020 Salzburg, Austria; Department of Surgery, State Hospital Hainburg, Hofmeisterstr. 70, 2410 Hainburg, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hausner
authors.affiliation: Division of Neuroanatomy, Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Muellerstrasse 59, 6020 Innsbruck, Austria.
authors.forename: Letizia
authors.initials: L
authors.lastname: Marvaldi
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Márton
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Pajer
authors.affiliation: Austrian Cluster of Tissue Regeneration and Ludwig Boltzmann Institute for Experimental and Clinical Traumatology at the Research Centre for Traumatology of the Austrian Workers' Compensation Board (AUVA), Donaueschingenstr. 13, 1200 Vienna, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hopf
authors.affiliation: Austrian Cluster of Tissue Regeneration and Ludwig Boltzmann Institute for Experimental and Clinical Traumatology at the Research Centre for Traumatology of the Austrian Workers' Compensation Board (AUVA), Donaueschingenstr. 13, 1200 Vienna, Austria; Vienna Private Clinic, Pelikangasse 15, 1090 Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Schmidhammer
authors.affiliation: Division of Neuroanatomy, Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Muellerstrasse 59, 6020 Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hausott
authors.affiliation: Austrian Cluster of Tissue Regeneration and Ludwig Boltzmann Institute for Experimental and Clinical Traumatology at the Research Centre for Traumatology of the Austrian Workers' Compensation Board (AUVA), Donaueschingenstr. 13, 1200 Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: Austrian Cluster of Tissue Regeneration and Ludwig Boltzmann Institute for Experimental and Clinical Traumatology at the Research Centre for Traumatology of the Austrian Workers' Compensation Board (AUVA), Donaueschingenstr. 13, 1200 Vienna, Austria; Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Hungary. Electronic address: nogradi.antal@med.u-szeged.hu.
authors.forename: Antal
authors.initials: A
authors.lastname: Nógrádi
authors.affiliation: Division of Neuroanatomy, Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Muellerstrasse 59, 6020 Innsbruck, Austria. Electronic address: lars.klimaschewski@i-med.ac.at.
authors.forename: Lars
authors.initials: L
authors.lastname: Klimaschewski
mesh_terms: D000200:Action Potentials; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007976:Leupeptins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D002154:Calpain; C032854:leupeptin
keywords: Axotomy; Leupeptin; Nerve lesion; Peripheral nervous system; Sciatic nerve