Interleukin-1β immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: Functional evidence for enhancement of electrographic seizures

Annamaria Vezzani, Mirko Conti, Ada De Luigi, Teresa Ravizza, Daniela Moneta, Francesco Marchesi, Maria Grazia De Simoni

Research output: Contribution to journalArticlepeer-review

Abstract

Using immunocytochemistry and ELISA, we investigated the production of interleukin (IL)-1β in the rat hippocampus after focal application of kainic acid inducing electroencephalographic (EEG) seizures and CA3 neuronal cell loss. Next, we studied whether EEG seizures per se induced IL-1β and microglia changes in the hippocampus using bicuculline as a nonexcitotoxic convulsant agent. Finally, to address the functional role of this cytokine, we measured the effect of human recombinant (hr)IL-1β on seizure activity as one marker of the response to kainate. Three and 24 hr after unilateral intrahippocampal application of 0.19 nmol of kainate, IL-1β immunoreactivity was enhanced in gila in the injected and the contralateral hippocampi. At 24 hr, IL-1β concentration increased by 16-fold (p <0.01) in the injected hippocampus. Reactive microglia was enhanced with a pattern similar to IL- 1β immunoreactivity. Intrahippocampal ap- plication of 0.77 nmol of bicuculline methiodide, which induces EEG seizures but not cell loss, enhanced IL-1β immunoreactivity and microglia, although to a less extent and for a shorter time compared with kainate. One nanogram of (hr)IL-1β intrahippocampally injected 10 min before kainate enhanced by 226% the time spent in seizures (p <0.01). This effect was blocked by coinjection of 1 μg (hr)IL-1β receptor antagonist or 0.1 ng of 3-((+)-2-carboxypiperazin-4-yl)- propyl-1-phosphonate, selective antagonists of IL-1β and NMDA receptors, respectively. Thus, convulsant and/or excitotoxic stimuli increase the production of IL-1β in microglia-like cells in the hippocampus. In addition, exogenous application of IL-1β prolongs kainate-induced hippocampal EEG seizures by enhancing glutamatergic neurotransmission.

Original languageEnglish
Pages (from-to)5054-5065
Number of pages12
JournalJournal of Neuroscience
Volume19
Issue number12
Publication statusPublished - Jun 15 1999

Keywords

  • Bicuculline
  • Cytokines
  • EEG
  • Epilepsy
  • Inflammation
  • Interleukin (IL)- 1Ra
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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