Affiliations: Department of Plastic, Hand and Reconstructive Surgery, Burn Center, BG-Trauma Center, Eberhard Karls University of Tübingen, Tübingen, Germany | Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, Germany | Dipartimento di Scienze Cliniche e Biologiche & Neuroscience Institute Cavalieri Ottolenghi, Universitá di Torino, Torino, Italy
Note: [] The first two authors equally contributed to this work. Corresponding author: Dr. Patrick Jaminet, M.D., Department of Plastic, Hand and Reconstructive Surgery, Burn Center, BG-Trauma Center, Eberhard-Karl University of Tübingen, Schnarrenbergstr. 95, 72076 Tübingen, Germany. Tel.: +49 7071 606 3886; Fax: +49 7071 606 1457; E-mail: [email protected]
Note: [] The first two authors equally contributed to this work.
Abstract: Background: Less is known about the role of Netrin-1 in the peripheral nervous system. In this study, we evaluated the role of Netrin-1 using the mouse median nerve model for assessment of peripheral nerve regeneration. Methods: Using real-time PCR and Western Blot analysis, we examined expression changes of Netrin-1 mRNA and Netrin-1 protein after transection and repair of the mouse median nerve in Wild-type animals. We further evaluated histomorphometrical changes as well as the functional recovery of the grasping force after median nerve transection and repair in WT mice and Netrin-1+/− heterozygous mice. Results: RT-PCR revealed a 1, 9 fold increase of Netrin-1 mRNA two weeks after nerve transection and repair in the nerve segment distal to the injury site. In Western blot analysis, we could show a high increase of Netrin-1 in the nerve segment distal to the injury site at day 14. Histomorphometrical analysis showed significantly higher cross sectional area and a lower fibre density in heterozygous Netrin-1+/− mice. Using the functional grasping test, we could show that peripheral nerve regeneration is significantly diminished in heterozygous Netrin-1+/− mice. Conclusions: Employing the mouse median nerve model in transgenic animals, we demonstrate that Netrin-1 plays an important role during peripheral nerve regeneration.
Keywords: Median nerve model, transgenic, peripheral nervous system, Netrin-1, grasping test
