Alpha-melanocyte stimulating hormone suppresses intracerebral tumor necrosis factor-alpha and interleukin-1beta gene expression following transient cerebral ischemia in mice

Neurosci Lett. 2002 Dec 16;334(3):186-90. doi: 10.1016/s0304-3940(02)01088-1.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Functional Laterality
  • Gene Expression / drug effects*
  • Infarction, Middle Cerebral Artery
  • Interleukin-1 / biosynthesis*
  • Ischemic Attack, Transient / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • Reperfusion / adverse effects
  • Telencephalon / drug effects
  • Telencephalon / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • alpha-MSH / pharmacology*


  • Analgesics, Non-Narcotic
  • Interleukin-1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • alpha-MSH