Document Detail

Delayed treatment with isoflurane attenuates lipopolysaccharide and interferon gamma-induced activation and injury of mouse microglial cells.
MedLine Citation:
PMID:  19672189     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Isoflurane pretreatment can induce protection against lipopolysaccharide and interferon gamma (IFNgamma)-induced injury and activation of mouse microglial cells. This study's goal was to determine whether delayed isoflurane treatment is protective.
METHODS: Mouse microglial cells were exposed to various concentrations of isoflurane for 1 h immediately after the initiation of lipopolysaccharide (10 or 1000 ng/ml) and IFNgamma (10 U/ml) stimulation or to 2% isoflurane for 1 h at various times after initiation of the stimulation. Nitrite production, lactate dehydrogenase release, and cell viability measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were assessed after stimulation with lipopolysaccharide and IFNgamma for 24 h. Inducible nitric oxide synthase (iNOS) protein expression was quantified by Western blotting. The iNOS expression in mouse brain was also studied.
RESULTS: Isoflurane applied 0 and 2 h after the initiation of lipopolysaccharide and IFNgamma stimulation improved cell viability. Isoflurane at 2%, but not at 1 or 3%, reduced the lipopolysaccharide and IFNgamma-induced nitrite production and decreased cell viability. Aminoguanidine, an iNOS inhibitor, also attenuated this decreased cell viability. Chelerythrine and bisindolylmalemide IX, protein kinase C inhibitors, abolished isoflurane effects on cell viability and iNOS expression after lipopolysaccharide and IFNgamma application. Isoflurane also decreased lipopolysaccharide-induced iNOS expression in mouse brain. Late isoflurane application to microglial cells reduced lipopolysaccharide and IFNgamma-induced lactate dehydrogenase release that was not inhibited by aminoguanidine.
CONCLUSIONS: These results suggest that delayed isoflurane treatment can reduce lipopolysaccharide and IFNgamma-induced activation and injury of microglial cells. These effects may be mediated by protein kinase C.
Jie-Ae Kim; Liaoliao Li; Zhiyi Zuo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  111     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-25     Completed Date:  2009-09-17     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  566-73     Citation Subset:  AIM; IM    
Department of Anesthesiology, University of Virginia, Charlottesville, Virginia 22908-0710, USA.
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MeSH Terms
Anesthetics, Inhalation / pharmacology*
Blotting, Western
Brain / drug effects,  enzymology
Cell Line
Cell Survival / drug effects
Cerebellum / cytology
Interferon-gamma / antagonists & inhibitors*,  toxicity
Isoflurane / pharmacology*
L-Lactate Dehydrogenase / blood
Lipopolysaccharides / antagonists & inhibitors*,  toxicity
Macrophage Activation / drug effects
Mice, Inbred C57BL
Microglia / drug effects*
Nitric Oxide Synthase Type II / biosynthesis
Nitrites / metabolism
Protein Kinase C / physiology
Grant Support
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Lipopolysaccharides; 0/Nitrites; 26675-46-7/Isoflurane; 82115-62-6/Interferon-gamma; EC Dehydrogenase; EC Oxide Synthase Type II; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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