Functional Recovery After Central Infusion of α-Melanocyte-Stimulating Hormone in Rats With Spinal Cord Contusion Injury

Abstract

Melanocortins, peptides related to α-melanocortin-stimulating hormone (αMSH) and adrenocorticotropic hormone (ACTH), are known to improve axonal regeneration following peripheral nerve injury and stimulate neurite outgrowth from central nervous system (CNS) neurons both in vitro and in vivo. The neurite outgrowth promoting capacity of αMSH has prompted us to investigate the effects of intrathecal application of αMSH on functional and electrophysiological recovery in a well– characterized model of spinal cord contusion injury. Different doses of αMSH were applied via osmotic minipumps into the cisterna magna for 10 days, thereby delivering the peptide directly into the CNS. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie, and Bresnahan locomotor rating scale, and the thoracolumbar height test. At the end of the study, electrophysiological analysis of rubrospinal motor evoked potentials as performed. Our data showed that application of 3.75 μg/kg/h αMSH resulted in a marked functional recovery, accompanied by a decrease in the latency of the rMEP. This study demonstrates that intrathecal application of αMSH results in functional recovery after spinal cord contusion injury. These findings may initiate new treatment strategies and/or the use of melanocortins in human spinal cord injury.