Antagonism of peripheral inflammation reduces the severity of status epilepticus

Nicola Marchi, Qingyuan Fan, Chaitali Ghosh, Vincent Fazio, Francesca Bertolini, Giulia Betto, Ayush Batra, Erin Carlton, Imad Najm, Tiziana Granata, Damir Janigro*

*Corresponding author for this work

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

Status epilepticus (SE) is one of the most serious manifestations of epilepsy. Systemic inflammation and damage of blood-brain barrier (BBB) are etiologic cofactors in the pathogenesis of pilocarpine SE while acute osmotic disruption of the BBB is sufficient to elicit seizures. Whether an inflammatory-vascular-BBB mechanism could apply to the lithium-pilocarpine model is unknown. LiCl facilitated seizures induced by low-dose pilocarpine by activation of circulating T-lymphocytes and mononuclear cells. Serum IL-1β levels increased and BBB damage occurred concurrently to increased theta EEG activity. These events occurred prior to SE induced by cholinergic exposure. SE was elicited by lithium and pilocarpine irrespective of their sequence of administration supporting a common pathogenetic mechanism. Since IL-1β is an etiologic trigger for BBB breakdown and its serum elevation occurs before onset of SE early after LiCl and pilocarpine injections, we tested the hypothesis that intravenous administration of IL-1 receptor antagonists (IL-1ra) may prevent pilocarpine-induced seizures. Animals pre-treated with IL-1ra exhibited significant reduction of SE onset and of BBB damage. Our data support the concept of targeting systemic inflammation and BBB for the prevention of status epilepticus.

Original languageEnglish (US)
Pages (from-to)171-181
Number of pages11
JournalNeurobiology of Disease
Volume33
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Anti-inflammatory therapy
  • Blood-brain barrier
  • Cerebrovascular function
  • Epilepsy
  • Inflammation
  • New drug targets
  • T lymphocytes

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Marchi, N., Fan, Q., Ghosh, C., Fazio, V., Bertolini, F., Betto, G., Batra, A., Carlton, E., Najm, I., Granata, T., & Janigro, D. (2009). Antagonism of peripheral inflammation reduces the severity of status epilepticus. Neurobiology of Disease, 33(2), 171-181. https://doi.org/10.1016/j.nbd.2008.10.002