Perioperative Medicine  |   July 2018
Noninvasive Tracking of Anesthesia Neurotoxicity in the Developing Rodent Brain
Author Notes
  • From the Department of Anesthesiology (R.M., G.E.), the Department of Psychology (J.R.), and the Center for Developmental Genetics (G.E.), Stony Brook Medicine, Stony Brook, New York; and the Department of Anesthesiology, Yale School of Medicine, New Haven, Connecticut (H.L., H.B.).
  • Part of the work presented in this article has been presented as an abstract at the Society for Neuroscience 2016 annual meeting in San Diego, California, November 15, 2016.
    Part of the work presented in this article has been presented as an abstract at the Society for Neuroscience 2016 annual meeting in San Diego, California, November 15, 2016.×
  • Submitted for publication October 4, 2017. Accepted for publication February 28, 2018.
    Submitted for publication October 4, 2017. Accepted for publication February 28, 2018.×
  • Address correspondence to Dr. Makaryus: Stony Brook Medicine, HSC, Level 4, Room 060, Stony Brook, New York, 11794–8480. rany.makaryus@stonybrookmedicine.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Basic Science / Central and Peripheral Nervous Systems
Perioperative Medicine   |   July 2018
Noninvasive Tracking of Anesthesia Neurotoxicity in the Developing Rodent Brain
Anesthesiology 7 2018, Vol.129, 118-130. doi:10.1097/ALN.0000000000002229
Anesthesiology 7 2018, Vol.129, 118-130. doi:10.1097/ALN.0000000000002229
Abstract

Background: Potential deleterious effect of multiple anesthesia exposures on the developing brain remains a clinical concern. We hypothesized that multiple neonatal anesthesia exposures are more detrimental to brain maturation than an equivalent single exposure, with more pronounced long-term behavioral consequences. We designed a translational approach using proton magnetic resonance spectroscopy in rodents, noninvasively tracking the neuronal marker N-acetyl-aspartate, in addition to tracking behavioral outcomes.

Methods: Trajectories of N-acetyl-aspartate in anesthesia naïve rats (n = 62, postnatal day 5 to 35) were determined using proton magnetic resonance spectroscopy, creating an “N-acetyl-aspartate growth chart.” This chart was used to compare the effects of a single 6-h sevoflurane exposure (postnatal day 7) to three 2-h exposures (postnatal days 5, 7, 10). Long-term effects on behavior were separately examined utilizing novel object recognition, open field testing, and Barnes maze tasks.

Results: Utilizing the N-acetyl-aspartate growth chart, deviations from the normal trajectory were documented in both single and multiple exposure groups, with z-scores (mean ± SD) of –0.80 ± 0.58 (P = 0.003) and –1.87 ± 0.58 (P = 0.002), respectively. Behavioral testing revealed that, in comparison with unexposed and single-exposed, multiple-exposed animals spent the least time with the novel object in novel object recognition (F(2,44) = 4.65, P = 0.015), traveled the least distance in open field testing (F(2,57) = 4.44, P = 0.016), but exhibited no learning deficits in the Barnes maze.

Conclusions: Our data demonstrate the feasibility of using the biomarker N-acetyl-aspartate, measured noninvasively using proton magnetic resonance spectroscopy, for longitudinally monitoring anesthesia-induced neurotoxicity. These results also indicate that the neonatal rodent brain is more vulnerable to multiple anesthesia exposures than to a single exposure of the same cumulative duration.