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Review: Effects of Anesthetics on Brain Circuit Formation

Wagner, Meredith MD*; Ryu, Yun Kyoung PhD; Smith, Sarah C. MD*; Mintz, Cyrus D. MD, PhD

Journal of Neurosurgical Anesthesiology: October 2014 - Volume 26 - Issue 4 - p 358–362
doi: 10.1097/ANA.0000000000000118
Departments: Supplement: Fourth Pediatric Anesthesia and Neuro-Development Assessment (PANDA) Symposium

The results of several retrospective clinical studies suggest that exposure to anesthetic agents early in life is correlated with subsequent learning and behavioral disorders. Although ongoing prospective clinical trials may help to clarify this association, they remain confounded by numerous factors. Thus, some of the most compelling data supporting the hypothesis that a relatively short anesthetic exposure can lead to a long-lasting change in brain function are derived from animal models. The mechanism by which such changes could occur remains incompletely understood. Early studies identified anesthetic-induced neuronal apoptosis as a possible mechanism of injury, and more recent work suggests that anesthetics may interfere with several critical processes in brain development. The function of the mature brain requires the presence of circuits, established during development, which perform the computations underlying learning and cognition. In this review, we examine the mechanisms by which anesthetics could disrupt brain circuit formation, including effects on neuronal survival and neurogenesis, neurite growth and guidance, formation of synapses, and function of supporting cells. There is evidence that anesthetics can disrupt aspects of all of these processes, and further research is required to elucidate which are most relevant to pediatric anesthetic neurotoxicity.

*Department of Anesthesiology, Columbia University, New York, NY

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, MD

Supported by NIH 1K08GM104329-01.

The authors have no conflicts of interest to disclose.

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

© 2014 by Lippincott Williams & Wilkins