Peripheral administration of Interleukin-1 Receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat

Exp Neurol. 1996 Apr;138(2):206-13. doi: 10.1006/exnr.1996.0059.

Abstract

We assessed the efficacy of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) on brain injury and edema formation after permanent middle cerebral artery occlusion (MCAo) in the rat. Previous studies showed that low amounts of rhIL-1ra injected directly into the brain significantly decreased infarct size after MCAo or excitotoxic injury in rats. Peripheral administration of rhIL-1ra (100 mg/kg sc at 0, 4, 8, 12, and 18 h after MCAo) significantly inhibited infarct size, by 46% (P < 0.05), measured at 24h. This was greater than the effect of MK801 administered immediately after MCAo (4 mg/kg ip, 0 h) which did not significantly reduce infarct size. rhIL-1ra (100 mg/kg also significantly inhibited cerebral edema formation by 49% (p< 0.05 measured 24 h after MCAo, but did not reduce edema formation measured 2 h after MCAo, but did not reduce edema formation measured 2 h after MCAo. Inhibition of infarction by rhIL-1ra was dependent on dose and time of administration. Together the results demonstrate that peripherally administered rhIL-1ra at high doses is able to mimic the efficacy of low dose of rhIL-1ra administered directly into the brain in a rodent model of stroke and that protection observed with rhIL-1ra was better than that offered by MK801 in this model.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Brain Damage, Chronic / prevention & control*
  • Brain Edema / prevention & control
  • Brain Ischemia / complications*
  • Cerebral Infarction / pathology
  • Dizocilpine Maleate / pharmacology
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Recombinant Proteins

Substances

  • Blood Glucose
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Dizocilpine Maleate