PMID- 12122053
OWN - NLM
STAT- MEDLINE
DCOM- 20020806
LR  - 20220330
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 22
IP  - 14
DP  - 2002 Jul 15
TI  - Interleukin-18 involvement in hypoxic-ischemic brain injury.
PG  - 5910-9
AB  - 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.
FAU - Hedtjarn, Maj
AU  - Hedtjarn M
AD  - Department of Physiology and Pharmacology, Perinatal Center, Goteborg University, 
      405 30 Goteborg, Sweden.
FAU - Leverin, Anna-Lena
AU  - Leverin AL
FAU - Eriksson, Kristina
AU  - Eriksson K
FAU - Blomgren, Klas
AU  - Blomgren K
FAU - Mallard, Carina
AU  - Mallard C
FAU - Hagberg, Henrik
AU  - Hagberg H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Il18r1 protein, mouse)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-18 Receptor alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-18)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Blotting, Western
MH  - Brain/blood supply/metabolism/pathology
MH  - Brain Chemistry
MH  - Caspase 1/genetics/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Hypoxia-Ischemia, Brain/*metabolism/pathology
MH  - Immunohistochemistry
MH  - Interleukin-1/metabolism
MH  - Interleukin-18/deficiency/genetics/*metabolism
MH  - Interleukin-18 Receptor alpha Subunit
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/metabolism/pathology
MH  - Neurons/metabolism/pathology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Interleukin/biosynthesis
MH  - Receptors, Interleukin-18
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC6757918
EDAT- 2002/07/18 10:00
MHDA- 2002/08/07 10:01
PMCR- 2003/01/15
CRDT- 2002/07/18 10:00
PHST- 2002/07/18 10:00 [pubmed]
PHST- 2002/08/07 10:01 [medline]
PHST- 2002/07/18 10:00 [entrez]
PHST- 2003/01/15 00:00 [pmc-release]
AID - 22/14/5910 [pii]
AID - 6587 [pii]
AID - 10.1523/JNEUROSCI.22-14-05910.2002 [doi]
PST - ppublish
SO  - J Neurosci. 2002 Jul 15;22(14):5910-9. doi: 10.1523/JNEUROSCI.22-14-05910.2002.