Intracerebral NMDA injection stimulates production of interleukin-1 beta in perinatal rat brain

J Neurochem. 1996 Nov;67(5):2215-8. doi: 10.1046/j.1471-4159.1996.67052215.x.

Abstract

Susceptibility to NMDA neurotoxicity peaks in the early postnatal period in rats. Although indirect evidence suggests that interleukin-1 beta is a mediator of NMDA neurotoxicity in perinatal rats, direct confirmation of NMDA-induced interleukin-1 beta production in the brain has not been reported previously. The primary goal of this study was to determine if intracerebral injection of a neurotoxic dose of NMDA stimulates interleukin-1 beta production acutely. We used a rat-specific interleukin-1 beta ELISA to quantify brain tissue homogenate interleukin-1 beta content, and an immunocytochemical assay with a monoclonal antirat interleukin-1 beta antibody to visualize its distribution. NMDA (10 nmol) was injected stereotaxically into 7-day-old rats, using coordinates that targeted the striatum and overlying dorsal hippocampus. Interleukin-1 beta concentrations were measured in samples from the injected and contralateral cerebral hemispheres 0-12 h later; In addition, the impact of treatment with the noncompetitive NMDA antagonist MK-801 on interleukin-1 beta production was assessed. We found marked increases in tissue content of interleukin-1 beta in the lesioned hemisphere; values peaked at 6 h post injection. Treatment with MK-801 (1 mg/kg) blocked NMDA-induced increases in interleukin-1 beta. Preliminary immunocytochemical analysis demonstrated high concentrations of interleukin-1 beta-immunoreactive cells in the lesioned hippocampus, and concurrent increases in interleukin-1 beta immunoreactivity diffusely in the ependyma at 6 h after NMDA administration. Our data provide the first direct evidence that NMDA-induced excitotoxic injury stimulates interleukin-1 beta production in vivo.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / drug effects*
  • Brain / immunology*
  • Brain / pathology
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Dizocilpine Maleate / pharmacology
  • Interleukin-1 / biosynthesis*
  • Microinjections
  • N-Methylaspartate / administration & dosage
  • N-Methylaspartate / pharmacology*
  • Neurotoxins / administration & dosage
  • Neurotoxins / pharmacology
  • Rats

Substances

  • Interleukin-1
  • Neurotoxins
  • N-Methylaspartate
  • Dizocilpine Maleate