Edinburgh Research Explorer

Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats

Research output: Contribution to journalArticle

  • Jesus M Pradillo
  • Adam Denes
  • Andrew D Greenhalgh
  • Herve Boutin
  • Caroline Drake
  • Barry W McColl
  • Eleanor Barton
  • Spencer D Proctor
  • James C Russell
  • Nancy J Rothwell
  • Stuart M Allan

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)1810-9
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number9
DOIs
Publication statusPublished - Sep 2012

Abstract

Many neuroprotective agents have been effective in experimental stroke, yet few have translated into clinical application. One reason for this may be failure to consider clinical comorbidities/risk factors in experimental models. We have shown that a naturally occurring interleukin-1 receptor antagonist (IL-1Ra) is protective against ischemic brain damage in healthy animals. However, protective effects of IL-1Ra have not been determined in comorbid animals. Thus, we tested whether IL-1Ra protects against brain injury induced by experimental ischemia in aged JCR-LA (corpulent) rats, which have clinically relevant risk factors. Male, aged, lean, and corpulent rats exposed to transient (90 minutes) occlusion of the middle cerebral artery (tMCAO) were administered two doses of IL-1Ra (25 mg/kg, subcutaneously) during reperfusion. Brain injury and neuroinflammatory changes were assessed 24 hours after tMCAO. Our results show that IL-1Ra administered at reperfusion significantly reduced infarct volume measured by magnetic resonance imaging (50%, primary outcome) and blood-brain barrier disruption in these comorbid animals. Interleukin-1Ra also reduced microglial activation, neutrophil infiltration, and cytokines levels in the brain. These data are the first to indicate that IL-1Ra protects against ischemic brain injury when administered via a clinically relevant route and time window in animals with multiple risk factors for stroke.

    Research areas

  • Animals, Blood-Brain Barrier, Brain, Brain Ischemia, Cytokines, Immunohistochemistry, Infarction, Middle Cerebral Artery, Inflammation, Interleukin 1 Receptor Antagonist Protein, Ischemic Attack, Transient, Lymphocyte Activation, Magnetic Resonance Imaging, Male, Microglia, Neuroprotective Agents, Neutrophil Infiltration, Rats, Recombinant Proteins, Reperfusion, Stroke, Treatment Outcome

ID: 13371354