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 (alpha-MSH), a tridecapeptide derived from proopiomelanocortin (POMC), on the neurodegeneration following global cerebral ischemia and reperfusion in the rat. The biological activities of alpha-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 a-MSH (intraperitoneally, i.p.) at 30 min, and 24, 48, 72 and 96 It post-ischemia. Stereological quantification of the pyramidal cells in the CAl 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 alpha-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 alpha-MSH, and the loss in body weight was reduced by a-MSH. In conclusion, post-ischemic administration of a-MSH was found to provide neuroprotection in the CAl pyramidal cell layer in the hippocampus, concomitant with a reduction in glial activation, indicating that alpha-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 a-MSH. (c) 2005 Elsevier Ltd. All rights reserved.