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

NEUROBIOLOGY OF DISEASE

卷:36

Article

Galic, M. A.²  Henderson, A. K.^2,3  Tsutsui, S.⁴  Pittman, Q. J.¹ 

[1] Univ Calgary, Fac Med, Dept Physiol & Pharmacol, Hlth Sci Ctr,Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada

[2] Univ Calgary, Hotchkiss Brain Inst, Epilepsy & Brain Circuits Program, Dept Neurosci, Calgary, AB T2N 4N1, Canada

[3] Univ Calgary, Hotchkiss Brain Inst, Dept Psychol, Calgary, AB T2N 4N1, Canada

[4] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada

关键词: Seizure;    Epilepsy;    Infection;    Inflammation;    Virus;    Cytokine;    Fever;    Hippocampus;    Glutamate receptor;    Minocycline;   

DOI  :  10.1016/j.nbd.2009.07.025

来源: Elsevier

【 摘 要 】

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)-1 beta 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-1 beta 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. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

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