title: Alpha-melanocyte stimulating hormone suppresses intracerebral tumor necrosis factor-alpha and interleukin-1beta gene expression following transient cerebral ischemia in mice.
abstract: Following stroke, an intracerebral inflammatory response develops that may contribute to postischemic central nervous system injury. This study's objective was to determine whether the anti-inflammatory neuropeptide alpha-melanocyte stimulating hormone (MSH) can suppress postischemic activation of intracerebral tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) gene expression. Ipsilateral TNF-alpha levels were increased in cerebrocortical territory of the middle cerebral artery (MCA) following transient unilateral MCA occlusion (MCAO) and reperfusion in mice, and systemic alpha-MSH treatment (0.5 mg/kg i.p.) suppressed this increase. Systemic alpha-MSH treatment also inhibited the marked increases in cortical TNF-alpha and IL-1beta mRNA levels following MCAO, and reduced the intracerebral TNF-alpha protein levels seen after transient global ischemia. We conclude that alpha-MSH treatment suppresses intracerebral proinflammatory cytokine gene expression following transient cerebral ischemia, suggesting that systemically administered melanocortins may exert neuroprotective effects in cerebral ischemia.
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, Department of Medicine and the Tupper Research Institute, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111, USA.
authors.forename: Qinheng
authors.initials: Q
authors.lastname: Huang
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Tatro
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D007839:Functional Laterality; D015870:Gene Expression / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery; D007375:Interleukin-1 / Q000096:biosynthesis*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015424:Reperfusion / Q000009:adverse effects; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D018712:Analgesics, Non-Narcotic; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH