Lithium protects against anaesthesia neurotoxicity in the infant primate brain

Kevin K. Noguchi, Stephen A. Johnson, Lauren E. Kristich, Lauren Drew Martin, Gregory Dissen, Emily A. Olsen, John W. Olney, Ansgar Brambrink

Research output: Contribution to journalArticle

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Abstract

Exposure of infant animals, including non-human primates (NHPs), to anaesthetic drugs causes apoptotic death of neurons and oligodendrocytes (oligos) and results in long-term neurodevelopmental impairment (NDI). Moreover, retrospective clinical studies document an association between anaesthesia exposure of human infants and significant increase in NDI. These findings pose a potentially serious dilemma because millions of human infants are exposed to anaesthetic drugs every year as part of routine medical care. Lithium (Li) at clinically established doses is neuroprotective in various cerebral injury models. We therefore investigated whether Li also protects against anaesthesia neurotoxicity in infant NHPs. On postnatal day 6 NHPs were anaesthetized with the widely used anaesthetic isoflurane (ISO) for 5 h employing the same standards as in a human pediatric surgery setting. Co-administration of Li completely prevented the acute ISO-induced neuroapoptosis and significantly reduced ISO-induced apoptosis of oligodendroglia. Our findings are highly encouraging as they suggest that a relatively simple pharmacological manipulation might protect the developing primate brain against the neurotoxic action of anaesthetic drugs while not interfering with the beneficial actions of these drugs. Further research is needed to determine Li's potential to prevent long-term NDI resulting from ISO anaesthesia, and to establish its safety in human infants.

Original languageEnglish (US)
Article number22427
JournalScientific Reports
Volume6
DOIs
StatePublished - Mar 8 2016

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Lithium
Primates
Isoflurane
Anesthesia
Anesthetics
Brain
Oligodendroglia
Cause of Death
Retrospective Studies
Pharmacology
Pediatrics
Apoptosis
Safety
Neurons
Wounds and Injuries
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Noguchi, K. K., Johnson, S. A., Kristich, L. E., Martin, L. D., Dissen, G., Olsen, E. A., ... Brambrink, A. (2016). Lithium protects against anaesthesia neurotoxicity in the infant primate brain. Scientific Reports, 6, [22427]. https://doi.org/10.1038/srep22427

Lithium protects against anaesthesia neurotoxicity in the infant primate brain. / Noguchi, Kevin K.; Johnson, Stephen A.; Kristich, Lauren E.; Martin, Lauren Drew; Dissen, Gregory; Olsen, Emily A.; Olney, John W.; Brambrink, Ansgar.

In: Scientific Reports, Vol. 6, 22427, 08.03.2016.

Research output: Contribution to journalArticle

Noguchi, KK, Johnson, SA, Kristich, LE, Martin, LD, Dissen, G, Olsen, EA, Olney, JW & Brambrink, A 2016, 'Lithium protects against anaesthesia neurotoxicity in the infant primate brain', Scientific Reports, vol. 6, 22427. https://doi.org/10.1038/srep22427
Noguchi, Kevin K. ; Johnson, Stephen A. ; Kristich, Lauren E. ; Martin, Lauren Drew ; Dissen, Gregory ; Olsen, Emily A. ; Olney, John W. ; Brambrink, Ansgar. / Lithium protects against anaesthesia neurotoxicity in the infant primate brain. In: Scientific Reports. 2016 ; Vol. 6.
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