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PMID: 12122053 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interleukin-18 involvement in hypoxic-ischemic brain injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 14 ·2002-07-15 ·Pages 5910-9

Hedtjärn M, Leverin AL, Eriksson K, Blomgren K, Mallard C, Hagberg H

Abstract

Inflammation is a critical factor for development of hypoxic-ischemic (HI) brain injury. Interleukin-18 (IL-18) is a proinflammatory cytokine expressed in microglia and processed by caspase-1. Our aim was to characterize the expression of IL-18 and its receptor in relation to caspase-1 and IL-1beta after HI and to evaluate to what extent IL-18 contributes to HI brain injury. Seven-day-old rats were subjected to HI, and brain tissue was sampled at different time points (3 hr to 14 d) after insult. The mRNA for IL-18 and caspase-1 were analyzed with reverse transcriptase PCR, protein was analyzed by Western blot (IL-18, caspase-1) or ELISA (IL-1beta), and the regional distribution was assessed by immunohistochemistry. HI was also induced in C57BL/6 mice, and brain injury in IL-18-deficient animals was compared with that in wild-type animals. The expression of mRNA/protein for caspase-1 and IL-18 in brain homogenates increased progressively at 12 hr to 14 d after HI, whereas IL-1beta peaked at 8 hr. A widespread expression of caspase-1 and IL-18 protein in microglia was found in the HI hemisphere. The IL-18 receptor was expressed on neurons of the cerebral cortex and thalamus. IL-1beta was primarily found in microglia in the habenular nucleus of the thalamus. The infarct volume was reduced by 21% (p = 0.01), and the neuropathology score was significantly decreased in the cerebral cortex (-35%), hippocampus (-22%), striatum (-18%), and thalamus (-17%) in mice with IL-18 deficiency compared with wild-type mice. In conclusion, we found that IL-18 expression in microglia was markedly increased after HI and that IL-18 appears to be important for the development of HI brain injury.

MeSH Terms
Animals Animals, Newborn Blotting, Western Brain/blood supply,metabolism,pathology Brain Chemistry Caspase 1/genetics,metabolism Disease Models, Animal Disease Progression Enzyme-Linked Immunosorbent Assay Female Hypoxia-Ischemia, Brain/metabolism,pathology Immunohistochemistry Interleukin-1/metabolism Interleukin-18/deficiency,genetics,metabolism Interleukin-18 Receptor alpha Subunit Male Mice Mice, Inbred C57BL Mice, Knockout Microglia/metabolism,pathology Neurons/metabolism,pathology RNA, Messenger/metabolism Rats Rats, Wistar Receptors, Interleukin/biosynthesis Receptors, Interleukin-18 Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Il18r1 protein, mouse Interleukin-1 Interleukin-18 Interleukin-18 Receptor alpha Subunit RNA, Messenger Receptors, Interleukin Receptors, Interleukin-18 Caspase 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hedtjärn Maj
Department of Physiology and Pharmacology, Perinatal Center, Göteborg University, 405 30 Göteborg, Sweden.
Leverin Anna-Lena
Eriksson Kristina
Blomgren Klas
Mallard Carina
Hagberg Henrik
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
20026587
Published
2002-07-15
Pages
5910-9
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6757918
Subset
IM
External Links
PubMed source DOI: 20026587 PMC Full Text View journal details
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