Document Detail

Dual effects of isoflurane on proliferation, differentiation, and survival in human neuroprogenitor cells.
MedLine Citation:
PMID:  23314167     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Previous studies have demonstrated that isoflurane can provide both neuroprotection and neurotoxicity in various tissue culture models and in rodent developing brains. The cellular and molecular mechanisms mediating these dual effects are not clear, but the exposure level and duration of isoflurane appear to be determinant factors.
METHODS: Using the ReNcell CX (Millipore, Billerica, MA) human neural progenitor cell line, the authors investigated the impact of prolonged exposure to varying isoflurane concentrations on cell survival and neurogenesis. In addition, the authors assessed the impact of short isoflurane preconditioning on elevation of cytosolic Ca concentration and cytotoxic effects mediated by prolonged isoflurane exposures and the contribution of inositol-1,4,5-trisphosphate or ryanodine receptor activation to these processes.
RESULTS: Short exposures to low isoflurane concentrations promote proliferation and differentiation of ReNcell CX cells, with no cell damage. However, prolonged exposures to high isoflurane concentrations induced significant ReNcell CX cell damage and inhibited cell proliferation. These prolonged exposures suppressed neuronal cell fate and promoted glial cell fate. Preconditioning of ReNcell CX cultures with short exposures to low concentrations of isoflurane ameliorated the effects of prolonged exposures to isoflurane. Pretreatment of ReNcell cultures with inositol-1,4,5-trisphosphate or ryanodine receptor antagonists mostly prevented isoflurane-mediated effects on survival, proliferation, and differentiation. Finally, isoflurane-preconditioned cultures showed significantly less isoflurane-evoked changes in calcium concentration.
CONCLUSION: The commonly used general anesthetic isoflurane exerts dual effects on neuronal stem cell survival, proliferation, and differentiation, which may be attributed to differential regulation of calcium release through activation of endoplasmic reticulum localized inositol-1,4,5-trisphosphate and/or ryanodine receptors.
Xuli Zhao; Zeyong Yang; Ge Liang; Zhen Wu; Yi Peng; Donald J Joseph; Saadet Inan; Huafeng Wei
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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:  118     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-04-19     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  537-49     Citation Subset:  AIM; IM    
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MeSH Terms
Calcium / metabolism
Cell Differentiation / drug effects*,  physiology
Cell Line, Transformed
Cell Proliferation / drug effects*
Cell Survival / drug effects*,  physiology
Fetal Stem Cells / drug effects*,  metabolism,  pathology
Isoflurane / pharmacology*,  toxicity
Neural Stem Cells / drug effects*,  metabolism,  pathology
Time Factors
Grant Support
Reg. No./Substance:
CYS9AKD70P/Isoflurane; SY7Q814VUP/Calcium
Comment In:
Anesthesiology. 2013 Mar;118(3):487-9   [PMID:  23299363 ]

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

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