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 3hours 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 500μg/kg) improved 24hour outcome in animals subjected to 2hours MCAO; α-MSH 500μg/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 3hours MCAO. The splenocyte response to phytohemagglutin in animals treated with α-MSH was attenuated at 24hours after MCAO. At 1 month after MCAO, treatment with α-MSH 500μg/kg at the time of stoke was associated with a decrease in TH1 response to myelin basic protein (MBP) in animals subjected to 2hours 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.