α-Melanocyte-stimulating hormone is neuroprotective in rat global cerebral ischemia

The aim of the study was to investigate the effects of alpha-melanocyte-stimulating hormone (α-MSH), a tridecapeptide derived from proopiomelanocortin (POMC), on the neurodegeneration following global cerebral ischemia and reperfusion in the rat. The biological activities of α-MSH include inhibition of inflammatory responses and anti-pyretic effects. Male Sprague-Dawley rats were subjected to four-vessel occlusion (4-VO) global cerebral ischemia followed by reperfusion, and treated with α-MSH (intraperitoneally, i.p.) at 30 min, and 24, 48, 72 and 96 h post-ischemia. Stereological quantification of the pyramidal cells in the CA1 area of the hippocampus showed that the number of viable neurons in ischemic rats was 96,945 ± 18,610 (means ± SD) as compared to 183,156 ± 49,935 in sham-operated rats (P < 0.05). The number of viable neurons after treatment of ischemic rats with α-MSH was 162,829 ± 34,757, i.e. significantly different from the number of viable neurons in ischemic rats injected with saline (P < 0.01). Astrocyte proliferation due to the ischemic insult was markedly reduced by the treatment with α-MSH, and the loss in body weight was reduced by α-MSH. In conclusion, post-ischemic administration of α-MSH was found to provide neuroprotection in the CA1 pyramidal cell layer in the hippocampus, concomitant with a reduction in glial activation, indicating that α-MSH or mimetics thereof may have a potential in the treatment of stroke or other neurodegenerative diseases. Further studies will be required to define the post-ischemic time window for administration of α-MSH.