Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats.
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.
Galic
M A
MA
Epilepsy and Brain Circuits Program, Hotchkiss Brain Institute, Department of Neuroscience, University of Calgary, Calgary, Alberta, Canada.
Riazi
K
K
Henderson
A K
AK
Tsutsui
S
S
Pittman
Q J
QJ
D000375:Aging / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D004198:Disease Susceptibility; D004660:Encephalitis / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*; D005260:Female; D006624:Hippocampus / Q000254:growth & development* / Q000473:pathology / Q000821:virology; D007858:Learning / Q000502:physiology; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000096:biosynthesis; D012640:Seizures / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology
D017470:Receptors, Glutamate