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Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice

Open access
Vezzani, A., Moneta, D., Conti, M., Richichi, C., Ravizza, T., De Luigi, A., De Simoni, M. G., Sperk, G., Andell-Jonsson, S., Lundkvist, J., Iverfeldt, K., Bartfai, T.·2000·Proceedings of the National Academy of Sciences

Abstract

IL-1β and its endogenous receptor antagonist (IL-1Ra) are rapidly induced by seizures in the rodent hippocampus. Exogenously applied IL-1β prolongs seizures in an IL-1R type I-mediated manner. This effect depends on N-methyl-d-aspartate receptor activation. We report here that intrahippocampal application of recombinant IL-1Ra or its selective endogenous overexpression in astrocytes under the control of glial acidic fibrillary protein promoter potently inhibits motor and electroencephalographic seizures induced by bicuculline methiodide in mice. Accordingly, transgenic mice show a reduced seizure-related c-fos mRNA expression in various forebrain areas compared with their wild-type littermates. Recombinant IL-1Ra was ineffective in mice deficient in IL-1R type I, having per se a delayed onset to generalized convulsions. These results demonstrate that IL-1Ra mediates potent anticonvulsant effects acting on IL-1R type I and suggest that the balance between brain IL-1β and IL-1Ra represents a crucial mechanism to control seizure generalization.

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Metadata

Authors
Vezzani, A., Moneta, D., Conti, M., Richichi, C., Ravizza, T., De Luigi, A., De Simoni, M. G., Sperk, G., Andell-Jonsson, S., Lundkvist, J., Iverfeldt, K., & Bartfai, T.
Venue
Proceedings of the National Academy of Sciences
Published
2000-10-03
Volume
97
Issue
21
Pages
11534-11539
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2148780480
Cited by
464
References
0
FWCI
6.46
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. https://app.cochat.ai/papers/10.1073/pnas.190206797
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Vezzani, A., Moneta, D., Conti, M., Richichi, C., Ravizza, T., De Luigi, A., De Simoni, M. G., Sperk, G., Andell-Jonsson, S., Lundkvist, J., Iverfeldt, K., & Bartfai, T. (2000). Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.190206797

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.