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Molecular Mechanisms of Anesthetic Neurotoxicity

A Review of the Current Literature

Jackson, William M. MD*; Gray, Christy D.B. MD, PhD; Jiang, Danye BS; Schaefer, Michele L. PhD; Connor, Caroline MD, PhD; Mintz, Cyrus D. MD, PhD

Journal of Neurosurgical Anesthesiology: October 2016 - Volume 28 - Issue 4 - p 361–372
doi: 10.1097/ANA.0000000000000348
Departments: Supplement: Proceedings of the Fifth PANDA Symposium on “Anesthesia and Neurodevelopment in Children”

Data from epidemiologic studies and animal models have raised a concern that exposure to anesthetic agents during early postnatal life may cause lasting impairments in cognitive function. It is hypothesized that this is due to disruptions in brain development, but the mechanism underlying this toxic effect remains unknown. Ongoing research, particularly in rodents, has begun to address this question. In this review we examine currently postulated molecular mechanisms of anesthetic toxicity in the developing brain, including effects on cell death pathways, growth factor signaling systems, NMDA and GABA receptors, mitochondria, and epigenetic factors. The level of evidence for each putative mechanism is critically evaluated, and we attempt to draw connections between them where it is possible to do so. Although there are many promising avenues of research, at this time no consensus can be reached as to a definitive mechanism of injury.

*Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, NY

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD

The authors have no funding or conflicts of interest to disclose.

Address correspondence to: Cyrus D. Mintz, MD, PhD, Department of Anesthesiology and Critical Care Medicine, Ross 370, 720 Rutland Ave., Johns Hopkins Medical Institutes, Baltimore, MD 21205 (e-mail:

Received July 8, 2016

Accepted July 11, 2016

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