alpha-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 alpha-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 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 alpha-MSH. In conclusion, post-ischemic administration of alpha-MSH was found to provide neuroprotection in the CA1 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 alpha-MSH.
Forslin Aronsson
Sa
S
Division of Experimental Geriatrics, Neurotec Department, Karolinska Institutet, Karolinska University Hospital, Novum, KFC, Level 4, SE-141 86 Stockholm, Sweden. asa.forslin-aronsson@ki.se
Spulber
Stefan
S
Popescu
Laurentiu M
LM
Winblad
Bengt
B
Post
Claes
C
Oprica
Mircea
M
Schultzberg
Marianne
M
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D000521:alpha-MSH