Assessment of general anaesthetic cytotoxicity in murine cortical neurones in dissociated culture

Abstract General anaesthetics are proposed to cause unconsciousness by modulating neuronal excitability in the mammalian brain through mechanisms that include enhancement of inhibitory GABAA receptor currents and suppression of excitatory glutamate receptor responses. Both intravenous and volatile a...

Full description

Saved in:

Bibliographic Details
Published in:	Toxicology (Amsterdam) Vol. 283; no. 1; pp. 1 - 7
Main Authors:	Campbell, Laura L, Tyson, Jennifer A, Stackpole, Emily E, Hokenson, Kristen E, Sherrill, Hanna, McKeon, Jeanne E, Kim, Sarah A, Edmands, Scott D, Suarez, Cristina, Hall, Adam C
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ireland Ltd 28-04-2011 Elsevier
Subjects:	Anaesthetics Anesthetics, General - toxicity Animals Animals, Newborn Biological and medical sciences brain cell death Cell Survival - drug effects Cerebral Cortex - cytology Cerebral Cortex - drug effects Cerebral Cortex - metabolism cytotoxicity Emergency gamma-Aminobutyric Acid - metabolism glutamic acid immunoassays In vitro intravenous injection isoflurane Isoflurane - toxicity ketamine Ketamine - toxicity L-Lactate Dehydrogenase - metabolism lactate dehydrogenase Medical sciences Mice Mice, Inbred C57BL Microscopy, Fluorescence Microtubule-Associated Proteins - metabolism N-Methylaspartate - metabolism Neurones neurons Neurons - cytology Neurons - drug effects Neurons - metabolism Neurotoxicity nitrous oxide Nitrous Oxide - toxicity Toxicology unconsciousness N-methyl- d-aspartate HRP Horseradish peroxidase Phosphate buffered saline TFA Minimum alveolar concentration DMEM LDH Neurotoxicity Neurones Trifluoroacetic acid MAP2 Parts per million NMDA NBM Gamma-aminobutyric acid Nuclear magnetic resonance Anaesthetics PBS Dulbecco's modified Eagle medium Glial fibrillary acidic protein Standard error of the mean ppm In vitro MAC GFAP DIV Neurobasal medium NMR Hank's balanced saline solution Microtubule associated protein 2 GABA Days in vitro SEM HBSS Lactose dehydrogenase Evaluation Nervous system diseases Toxicity Rodentia Cytotoxicity Vertebrata Mammalia General anesthetic Mouse Animal
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract General anaesthetics are proposed to cause unconsciousness by modulating neuronal excitability in the mammalian brain through mechanisms that include enhancement of inhibitory GABAA receptor currents and suppression of excitatory glutamate receptor responses. Both intravenous and volatile agents may produce neurotoxic effects during early postnatal rodent brain development through similar mechanisms. In the following study, we investigated anaesthetic cytotoxicity in primary cortical neurones and glia from postnatal day 2–8 mice. Cultures at 4–20 days in vitro were exposed to combinations of ketamine (100 μM to 3 mM), nitrous oxide (75%, v/v) and/or isoflurane (1.5–5%, v/v) for 6–12 h. Neuronal survival and cell death were measured via microtubule associated protein 2 immunoassay and lactate dehydrogenase release assays, respectively. Clinically relevant anaesthetic concentrations of ketamine, nitrous oxide and isoflurane had no significant neurotoxic effects individually or when given as anaesthetic cocktails, even with up to 12 h exposure. This lack of neurotoxicity was observed regardless of whether cultures were prepared from postnatal day 0–2 or day 8 mice, and was also unaffected by number of days in vitro (DIV 4–20). Significant neurotoxic effects were only observed at supraclinical concentrations ( e.g. 1–3 mM ketamine). Our study suggests that neurotoxicity previously reported in vivo is not due to direct cytotoxicity of anaesthetic agents, but results from other impacts of the anaesthetised state during early brain development.
Bibliography:	http://dx.doi.org/10.1016/j.tox.2011.01.014 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2011.01.014