Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats

Neurobiol Dis. 2009 Nov;36(2):343-51. doi: 10.1016/j.nbd.2009.07.025. Epub 2009 Aug 4.

Abstract

Viral infections of the CNS and their accompanying inflammation can cause long-term neurological effects, including increased risk for seizures. To examine the effects of CNS inflammation, we infused polyinosinic:polycytidylic acid, intracerebroventricularly to mimic a viral CNS infection in 14 day-old rats. This caused fever and an increase in the pro-inflammatory cytokine, interleukin (IL)-1beta in the brain. As young adults, these animals were more susceptible to lithium-pilocarpine and pentylenetetrazol-induced seizures and showed memory deficits in fear conditioning. Whereas there was no alteration in adult hippocampal cytokine levels, we found a marked increase in NMDA (NR2A and C) and AMPA (GluR1) glutamate receptor subunit mRNA expression. The increase in seizure susceptibility, glutamate receptor subunits, and hippocampal IL-1beta levels were suppressed by neonatal systemic minocycline. Thus, a novel model of viral CNS inflammation reveals pathophysiological relationships between brain cytokines, glutamate receptors, behaviour and seizures, which can be attenuated by anti-inflammatory agents like minocycline.

Publication types

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

MeSH terms

  • Aging / pathology*
  • Animals
  • Animals, Newborn
  • Disease Susceptibility
  • Encephalitis / pathology*
  • Encephalitis / physiopathology
  • Encephalitis / virology*
  • Female
  • Hippocampus / growth & development*
  • Hippocampus / pathology
  • Hippocampus / virology
  • Learning / physiology
  • Male
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / biosynthesis
  • Seizures / etiology
  • Seizures / pathology*
  • Seizures / physiopathology

Substances

  • Receptors, Glutamate