RESEARCH ARTICLE
Isoflurane but not Fentanyl Causes Apoptosis in Immature Primary Neuronal Cells
Monika Berns1, *, Anna Christine Wolter1, Christoph Bührer1, Stefanie Endesfelder1, Thoralf Kerner2
Article Information
Identifiers and Pagination:
Year: 2017Volume: 11
First Page: 39
Last Page: 47
Publisher ID: TOATJ-11-39
DOI: 10.2174/1874321801711010039
Article History:
Received Date: 29/12/2016Revision Received Date: 03/03/2017
Acceptance Date: 09/03/2017
Electronic publication date: 31/07/2017
Collection year: 2017
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background:
Anaesthetics are widely used in new-borns and preterm infants, although it is known that they may adversely affect the developing brain.
Objective:
We assessed the impact of the volatile anaesthetic, isoflurane, and the intravenous analgesic, fentanyl, on immature and mature embryonic neuronal cells.
Methods:
Primary neuronal cultures from embryonic rats (E18) cultured for 5 (immature) or 15 days (mature) in vitro (DIV), respectively, were exposed to isoflurane (1.5 Vol.%) or fentanyl (0.8 - 200 ng/ml) for 24 hours. Experiments were repeated in the presence of the γ-amino butyric acid-A (GABAA) receptor antagonists, bicuculline or picrotoxin (0.1 mmol/l), or the pancaspase inhibitor zVAD-fmk (20 nmol/l). Cell viability was assessed by methyltetrazolium (MTT) metabolism or lactate dehydrogenase (LDH) release.
Results:
Isoflurane reduced cell viability significantly in primary neuronal cells cultured for 5 DIV (Δ MTT -28 ±13%, Δ LDH +143 ±15%). Incubation with bicuculline, picrotoxin or zVAD-fmk protected the cells mostly from isoflurane toxicity. After 15 DIV, cell viability was not reduced by isoflurane. Viability of primary neurons cultured for 5 DIV did not change with fentanyl over the wide range of concentrations tested.
Conclusion:
Immature primary neurons may undergo apoptosis following exposure to isoflurane but are unaffected by fentanyl. Mature primary neurons were not affected by isoflurane exposure.