α-MSH: a potential neuroprotective and immunomodulatory agent for the treatment of stroke.
Alpha-melanocyte-stimulating hormone (MSH) is a neuropeptide with profound immunomodulatory properties; we evaluated the effects of α-MSH on stroke outcome and its ability to modulate the postischemic immune response. In Lewis rats subjected to 3 hours of middle cerebral artery occlusion (MCAO), plasma concentrations of α-MSH rapidly decreased and returned to baseline over the course of days. Exogenous administration of α-MSH (100 or 500 μg/kg) improved 24 hour outcome in animals subjected to 2 hours MCAO; α-MSH 500 μg/kg also decreased infarct volume at this time point. Both doses of α-MSH were ineffective in improving outcome or decreasing infarct volume in animals subjected to 3 hours MCAO. The splenocyte response to phytohemagglutin in animals treated with α-MSH was attenuated at 24 hours after MCAO. At 1 month after MCAO, treatment with α-MSH 500 μg/kg at the time of stoke was associated with a decrease in TH1 response to myelin basic protein (MBP) in animals subjected to 2 hours MCAO, although treatment was not associated with improved outcome at this time point. Given the early benefits of α-MSH treatment and its effect on immunologic outcome, further studies to evaluate the utility of α-MSH for the treatment of cerebral ischemia are warranted.
Savos
Anna V
AV
Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.
Gee
J Michael
JM
Zierath
Dannielle
D
Becker
Kyra J
KJ
D000818:Animals; D001921:Brain / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D007155:Immunologic Factors; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D018696:Neuroprotective Agents; D010835:Phytohemagglutinins / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000473:pathology; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D016896:Treatment Outcome; D000521:alpha-MSH / Q000097:blood / Q000494:pharmacology*
D007155:Immunologic Factors; D018991:Myelin Proteolipid Protein; D018696:Neuroprotective Agents; D010835:Phytohemagglutinins; D000521:alpha-MSH