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

Abstract

Melanocortins, peptides related to alpha-melanocortin-stimulating hormone (alpha MSH) 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 alpha MSH has prompted us to investigate the effects of intrathecal application of alpha MSH on functional and electrophysiological recovery in a well-characterized model of spinal cord contusion injury. Different doses of alpha MSH 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 micrograms/kg/h alpha MSH resulted in a marked functional recovery, accompanied by a decrease in the latency of the rMEP. This study demonstrates that intrathecal application of alpha MSH 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.

Melanocortins applied intravitreally delay retinal dystrophy in Royal College of Surgeons rats

“…MSH and its analog promote growth of injured peripheral neurons in vivo [1,9,10,30] and in vitro [31], induce outgrowth of neurites from the central nervous system [1,13,16,31], and accelerate recovery of brain and spinal cord damage. Therefore, photoreceptor rescue revealed in MA-treated retinae in vivo is possibly not only injury related but may also be supplemented by MA neurotrophic activity [4,20]. The neurotrophic effect of MSH is receptor specific [2,3] and is not duplicated by ACTH or glucocorticoids [18,25].…”

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

“…Reproduced from Rajora et al, 1996, with permission. 18 Dekker, 1988;Van der Zee et al, 1988;Strand et al, 1989Strand et al, , 1993Strand et al, , 1994Antonawich et al, 1994;Hol et al, 1994;Laquerriere et al, 1994;Plantinga et al, 1995;van de Meent et al, 1997;Joosten et al, 1999;Lankhorst et al, 1999Lankhorst et al, , 2000van der Kraan et al, 1999). A recent study shows that also melanotan II has potent influences in nerve regeneration and neuroprotection (Ter Laak et al, 2003).…”

Neuroprotective Effects of Melanocortins in CNS Injury

“…Clinically used analgesics acting on the kappa-opioid receptor (and having affinity for the mu-opiod receptor) have been reported to be more effective in women than in men [16,92]. Via quantitative trait locus mapping followed by a candidate gene strategy and pharmacological tools, the MC1R has been proposed to mediate kappa-opioid analgesia in females [16].…”

“…It appears that the melanocortins, like -MSH are involved in regeneration or repair mechanisms following peripheral nerve or spinal cord injury [15][16]. Thus, intrathecal application of -MSH in a model of spinal cord contusion injury results in both functional and electrophysiological recoveries [4,16,18,19].…”