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

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.

• Authors: M A Galic, K Riazi, A K Henderson, S Tsutsui, Q J Pittman
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 36 Issue 2 Pg. 343-51 (Nov 2009) ISSN: 1095-953X [Electronic] United States
• PMID: 19660546 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Glutamate

Topics

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