Org.2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat.
The beneficial effect of short-term (8 days) melanocortin therapy on regenerating peripheral nerves is demonstrated using functional and electrophysiological tests. Following a crush lesion of the rat sciatic nerve, recovery of sensory function is monitored by assessing the responsiveness of the rat to a small electric current applied to the footsole. Recovery of motor function is assessed by means of an analysis of walking patterns. Normalization of the walking pattern reflects reinnervation of different muscle groups. The motor and H-reflex related sensory nerve conduction velocity of the regenerated nerves are longitudinally investigated in the same rats in which the recovery of motor and sensory function had been assessed previously. Functional tests show an enhanced recovery under melanocortin therapy, but in the end both saline- and melanocortin-treated rats show 100% recovery. However, when compared to the contralateral sciatic nerve, in the peptide-treated animals motor nerve conduction in the regenerated nerves has fully recovered after about 90 days following the crush lesion and the sensory conduction after about 120 days, whereas in the saline-treated rats a deficit of 20-40% in both motor and sensory conduction remains. This difference is observed even 214 days following crush.
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Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands.
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D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D009046:Motor Neurons / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects*; D013997:Time Factors
D000927:Anticonvulsants; D010446:Peptide Fragments; D010455:Peptides; C013765:Org 2766; D000324:Adrenocorticotropic Hormone