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Etomidate exposure in early infant mice (P10) does not induce apoptosis or affect behaviour
Karolinska Univ Hosp, Astrid Lindgrens Childrens Hosp, Dept Paediat Anaesthesia & Intens Care, S-17176 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Karolinska Univ Hosp, Astrid Lindgrens Childrens Hosp, Dept Paediat Anaesthesia & Intens Care, S-17176 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
2016 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 5, 588-596 p.Article in journal (Refereed) Published
Abstract [en]

Background

Numerous animal studies have shown that all commonly used intravenous anaesthetic drugs and volatile agents may cause neuronal apoptosis following exposure in early life. Most studies have focussed on detecting increased apoptosis but their methods are not always readily transferrable to humans.

The lipid formulation of etomidate represents an alternative to the currently established intravenous anaesthetic agents but there is no animal or human data on apoptosis or long-term behavioural changes. The aim of our study was to investigate the effects of etomidate on cerebral neuronal apoptosis and long-term behavioural effects using an established mouse model that represents the clinically relevant period of anaesthesia during early infancy in humans.

Methods

Six groups of 10 day old mice (P10) were injected with either etomidate 0.3, 3 or 10 mg/kg, propofol 60 mg/kg, ketamine 50 mg/kg or placebo only. Apoptosis in the cerebral cortex and hippocampus was assessed 24 h after treatment (activated caspase-3). Late behavioural effects were tested at 2 months of age (spontaneous activity in a new environment).

Results

No evidence was found of differences in activated caspase 3-concentrations among the study groups. Significant late behavioural changes were only observed in the ketamine group.

Conclusion

A single dose of etomidate in early infant mice at P10 did not produce evidence of cerebral apoptosis or impaired adult motor behaviour.

Place, publisher, year, edition, pages
2016. Vol. 60, no 5, 588-596 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-289308DOI: 10.1111/aas.12685ISI: 000373773700005PubMedID: 26763687OAI: oai:DiVA.org:uu-289308DiVA: diva2:925013
Available from: 2016-04-29 Created: 2016-04-29 Last updated: 2016-06-02Bibliographically approved

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