Local administration of DFO-loaded lipid particles improves recovery after end-to-end reconstruction of rat median nerve.
OBJECTIVE
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 Finally, the repaired nerves were withdrawn for immunocytochemistry with a neurofilament antibody and axon quantitative morphology.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.
Sinis
Nektarios
N
Klinik für Hand-, Plastische-, Rekonstruktive- und Verbrennungschirurgie, Universität Tübingen, BG-Unfallklinik, Germany. nsinis@bgu-tuebingen.de
Di Scipio
Frederica
F
Schönle
Phillip
P
Werdin
Frank
F
Kraus
Armin
A
Koopmanns
Guido
G
Masanneck
Carmen
C
Hermanns
Susanne
S
Danker
Timm
T
Guenther
Elke
E
Haerle
Max
M
Schaller
Hans-Eberhard
HE
Geuna
Stefano
S
Mueller
Hans-Werner
HW
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology; D020423:Median Neuropathy / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D017262:Siderophores / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D008055:Lipids; D016900:Neurofilament Proteins; D017262:Siderophores; C051774:neurofilament protein H; D003676:Deferoxamine