Local administration of DFO-loaded lipid particles improves recovery after end-to-end reconstruction of rat median nerve

Issue title: Anniversary Issue: Celebrating 20 years of Restorative Neurology and Neuroscience

Article type: Research Article

Authors: Sinis, Nektarios | Di Scipio, Frederica | Schönle, Phillip | Werdin, Frank | Kraus, Armin | Koopmanns, Guido | Masanneck, Carmen | Hermanns, Susanne | Danker, Timm | Guenther, Elke | Haerle, Max | Schaller, Hans-Eberhard | Geuna, Stefano | Mueller, Hans-Werner

Affiliations: Klinik für Hand-, Plastische-, Rekonstruktive- und Verbrennungschirurgie, Universität Tübingen, BG-Unfallklinik, Tübingen, Germany | Dipartimento di Scienze Cliniche e Biologiche, University de Torino, Ospedale San Luigi, Orbassano, Italy | Neuraxo Biopharmaceuticals, Düsseldorf, Erkrath, Germany | Natruwissenschaftliches und Medizinisches Institut, Reutlingen, Germany | Orthopädische Klinik Markgrönngen, Klinik für Hand- und Plastische Chirurgie, Düsseldorf, Germany | Labor für Molekulare Neurobiologie, Neurologische Klinik der Universität Düsseldorf, Düsseldorf, Germany

Note: [] Corresponding author: Dr. Nektarios Sinis, Klinik für Hand-, Plastische-, Rekonstruktive und Verbrennungschirurgie, Berufsgenossenschaftliche Unfallklinik, Schnarrenberg 95, D-72076 Tübingen, Germany. Tel.: +49 7071 606 1199; Fax: +49 7071 606 1189; E-mail: [email protected]

Abstract: Purpose: The improvement of regeneration and functional recovery after peripheral nerve injury is a major challenge in neurosurgery. Although microsurgical techniques for nerve reconstruction have seen great advancements over the last years, the clinical outcome with patients is often unsatisfactory. The aim of the present study was to investigate if administration of the iron chelator Deferroxamine (DFO), can improve postoperative outcome in the rat median nerve reconstruction model. Methods: After complete transection, the right median nerve was repaired by end-to-end neurorrhaphy. The suture site was wrapped by a 1-cm-long external jugular vein segment, either empty or filled with DFO-loaded lipid particles (Perineurin© or with a vehicle (unloaded lipid particles) alone. Functional testing was carried out weekly by means of the grasping test. At the time of withdrawal, 12 weeks post-operatively, muscle tropism recovery was assessed by weighing flexor digitorum sublimis muscle that is innervated by the median nerve only. Before harvesting of the nerve specimens electrophysiological analyses were performed with measuring the latency, the threshold and the conduction velocity. Finally, the repaired nerves were withdrawn for immunocytochemistry with a neurofilament antibody and axon quantitative morphology. Results: The comparison between the groups showed that intraoperative application of the DFO-loaded lipid particles at the neurorrhaphy site led to a significant increase in the density of regenerating axons as well as to an accelerated recovery of both muscle tropism and motor function. The electrophysiological results demonstrated a decrease of the threshold, a lower latency, and a higher conduction velocity in the Perineurin©-treated animals. Conclusions: The results of the present study suggest that local administration of Perineurin© might have a therapeutic potential for improving the postoperative outcome after microsurgical nerve reconstruction in patients.

Keywords: Primary nerve suture, iron chelator, nerve regeneration, median nerve

DOI: 10.3233/RNN-2009-0517

Journal: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 653-664, 2009