Effects of sevoflurane on primary neuronal cultures of  embryonic rats.
OBJECTIVE
Commonly used anaesthetics can cause neurodegeneration in the developing brain. Sevoflurane, a widely used substance in paediatric anaesthesia, has not been analysed thus far. This study was carried out to investigate the effects of sevoflurane on neuronal cell viability.


METHODS
Primary cortical neuronal cultures were prepared from Wistar rat embryos (E18), kept in 100 microl Gibco-Neurobasal-A medium and exposed to 4 and 8 Vol.% sevoflurane for up to 48 h. Cell viability was assessed using the methyltetrazolium assay and was related to untreated controls. To evaluate the role of gamma-aminobutyric acid type A receptors, untreated cells were preincubated with the receptor antagonists gabazine or picrotoxin and were subsequently exposed to 8 Vol.% sevoflurane and the receptor antagonist. Cell viability was assessed and compared with that of sevoflurane-treated controls.


RESULTS
Up to 6 (8 Vol.%) and 12 h (4 Vol.%) of exposure to sevoflurane, cell viability was equal when compared with untreated controls. Only longer exposure times led to significantly lowered cell viability. After 12 h of exposure, no significant differences in cell viability were found between these two series. Cell viability of cultures treated with sevoflurane and the receptor antagonists showed no significant differences when compared with sevoflurane-exposed controls.


CONCLUSIONS
These results suggest that sevoflurane does not cause neurodegeneration in primary cortical neurons of the rat following clinically relevant exposure times and concentrations.
Berns
Monika
M
Klinik für Neonatologie, Campus Virchow-Klinikum, Charité Centrum 17 für Frauen-, Kinder- und Jugendmedizin mit Perinatalzentrum und Humangenetik, Berlin, Germany. monika.berns@charite.de
Zacharias
Robert
R
Seeberg
Lucas
L
Schmidt
Maren
M
Kerner
Thoralf
T
D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D008738:Methyl Ethers / Q000008:administration & dosage / Q000009:adverse effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D000077149:Sevoflurane; D013997:Time Factors
D018685:Anesthetics, Inhalation; D018756:GABA Antagonists; D008738:Methyl Ethers; D010852:Picrotoxin; D011724:Pyridazines; D011963:Receptors, GABA-A; D000077149:Sevoflurane; C049853:gabazine