Effects of chronic overexpression of interleukin-1 receptor antagonist in a model of permanent focal cerebral ischemia in mouse

Mircea Oprica, Anne-Marie Van Dam, Johan Lundkvist, Kerstin Iverfeldt, Bengt Winblad, Tamas Bartfai, Marianne Schultzberg

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Interleukin-1 receptor antagonist (IL-1ra) has been shown previously to have neuroprotective effects in animal models of stroke. The effects of chronic overexpression of human soluble IL-1ra (hsIL-1ra) were studied in a mouse model of permanent focal cerebral ischemia. A transgenic mouse strain (Tg hsIL-1ra+/-) has been developed using the promoter for glial fibrillary acidic protein (GFAP) to limit the overexpression to the CNS. Analysis of the neurological scores, infarct volume and edema formation revealed no differences between Tg hsIL-1ra+/- and wild-type (WT) mice. The cerebral ischemia resulted in pronounced astrocyte proliferation and microglial activation, as well as induction of inflammatory markers in both Tg hsIL-1ra+/- and WT mice, with no major differences between the two genotypes. Interestingly, hsIL-1ra expression in astrocytes was reduced in infarcted areas as compared to non-ischemic regions and sham-operated controls. In conclusion, transgenic overexpression of hsIL1-ra was not neuroprotective in this cerebral ischemia model, possibly due to insufficient levels for protection against the extensive lesion, or an up-regulation of compensatory inflammatory signals due to the lifetime blockade of IL-1 receptors.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalActa Neuropathologica
Issue number1
Publication statusPublished - Jul 2004


  • Animals
  • Brain Edema
  • Brain Infarction
  • Brain Ischemia
  • Caspase 1
  • Comparative Study
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein
  • Infarction, Middle Cerebral Artery
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Journal Article
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuroglia
  • Neurologic Examination
  • Regional Blood Flow
  • Research Support, Non-U.S. Gov't
  • Sialoglycoproteins

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