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Suppression of Fibrous Scar Improves Peripheral Nerve Regeneration After Primary Nerve Suture<br />

Institution where the work was prepared: University of Tuebingen and University of Duesseldorf, Tuebingen and<br />

Duesseldorf, Germany<br />

Nektarios Sinis, MD1; Philip Schoenle1; Tatjana Lanaras1; Frank Werdin, MD1; Armin Kraus, MD1; Max Haerle, MD2;<br />

Timm Danker, PhD1; Elke Guenther, Phd1; Federica Di Scipio, Phd3; Stefano Geuna, MD3; Hans-Werner Mueller,<br />

PhD4; Daniela Mueller5; Carmen Masannek5; Susanne Hermanns, Phd5; Hans-Eberhard Schaller, MD1; (1)University of<br />

Tuebingen, (2)Orthopaedische Klinik Markgroeningen, (3)University de Torino, (4)Heinrich-Heine-University of<br />

Duesseldorf, (5)Neuraxo Biopharmaceuticals GmbH<br />

BACKGROUND:<br />

Despite the progress of microsurgical techniques the outcome of repaired nerves after primary nerve suture remains incomplete in a<br />

lot of cases. One reason that explains these results is the development of a fibrous collagen scar at the site of coaptation with expression<br />

of different growth inhibiting substances. This collagen scar prevents axons from passing the lesion and reaching the end organ.<br />

The aim of this study was to analyze the impact of a scar inhibiting substance, namely a potent iron chelator on peripheral nerves after<br />

transection and primary nerve suture.<br />

MATERIAL/ METHODS:<br />

In a rat median nerve model four experimental groups were operated. Group I ñ transection of the median nerve and primary nerve<br />

suture (N = 12). Group II ñ transection and venous ensheatment of the median nerve at the coaptation site (external jugular vein) (N =<br />

12). Group III ñ transection of the nerve, venous ensheatment and filling the vein with a lipid carrier (N = 12). Group IV ñ transection,<br />

venous ensheatment, filling of the vein with the iron chelator combined with the lipid carrier (N = 12). The observation† Axon number,<br />

density, average diameter, nerve area and myelin thickness were measured. The gastrocnemius muscle was harvested and gene expression<br />

of GAP-43, myogenin, MyoD, MYF5, MYF6 (MRF4) and the ?, ?, ?, ?, and ?-subunits of the nicotinic acetlycholinergic<br />

receptor(nAChR) were examined.<br />

RESULTS:<br />

For control animals, 83% of Young showed evidence of regeneration vs. 50% of Aged. For IGF-1 treated animals, 100% of Young and<br />

75% of Aged showed evidence of regeneration. Of regenerated animals, there was no difference in conduction delay or amplitude. In<br />

aged animals, IGF-1 significantly increased a) axons per nerve (13025 vs. 3062; p

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