Newly Published
Perioperative Medicine  |   August 2019
Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats
Author Notes
  • From the Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota (K.J.S.); Department of Anesthesiology, ThedaCare Regional Medical Center, Appleton, Wisconsin (B.M.M.); Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (B.J.I., N.H., J.K.); Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, Pennsylvania (E.B.R.); Department of Preventive Medicine Biostatistics Faculty, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.-C.A.); and the Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (K.J.H.)
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Part of the work presented in this article has been presented as an abstract at the International Anesthesia Research Society annual meeting in San Diego, California, May 4, 2013.
    Part of the work presented in this article has been presented as an abstract at the International Anesthesia Research Society annual meeting in San Diego, California, May 4, 2013.×
  • Submitted for publication October 15, 2018. Accepted for publication June 17, 2019.
    Submitted for publication October 15, 2018. Accepted for publication June 17, 2019.×
  • Correspondence: Address correspondence to Dr. Hogan: Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, B6/319 Clinical Sciences Center, 600 Highland Avenue, Madison, Wisconsin 53792. khogan@wisc.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 / Central and Peripheral Nervous Systems / Trauma / Burn Care
Perioperative Medicine   |   August 2019
Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats
Anesthesiology Newly Published on August 30, 2019. doi:10.1097/ALN.0000000000002906
Anesthesiology Newly Published on August 30, 2019. doi:10.1097/ALN.0000000000002906
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Nitrous oxide exposure can induce spinal cord neurodegeneration and related neuropathy in humans rendered susceptible by genetic or acquired risk factors

  • The effects of nitrous oxide on the regeneration of nervous system following trauma has not been previously reported

What This Article Tells Us That Is New:

  • In in vitro and in vivo experimental models of male rats, nitrous oxide exposure impairs folic acid-induced axonal regeneration of dorsal root and retinal ganglion neurons

  • The beneficial effects of folic acid on functional recovery following spinal cord contusion in male rats are hindered by co-administration of nitrous oxide

  • These experiments suggest that nitrous oxide can interfere with axonal regeneration and functional recovery following central nervous system injury

Background: Nitrous oxide can induce neurotoxicity. The authors hypothesized that exposure to nitrous oxide impairs axonal regeneration and functional recovery after central nervous system injury.

Methods: The consequences of single and serial in vivo nitrous oxide exposures on axon regeneration in four experimental male rat models of nervous system injury were measured: in vitro axon regeneration in cell culture after in vivo nitrous oxide administration, in vivo axon regeneration after sharp spinal cord injury, in vivo axon regeneration after sharp optic nerve injury, and in vivo functional recovery after blunt contusion spinal cord injury.

Results: In vitro axon regeneration 48 h after a single in vivo 70% N2O exposure is less than half that in the absence of nitrous oxide (mean ± SD, 478 ± 275 um; n = 48) versus 210 ± 152 um (n = 48; P < 0.0001). A single exposure to 80% N2O inhibits the beneficial effects of folic acid on in vivo axonal regeneration after sharp spinal cord injury (13.4 ± 7.1% regenerating neurons [n = 12] vs. 0.6 ± 0.7% regenerating neurons [n = 4], P = 0.004). Serial 80% N2O administration reverses the benefit of folic acid on in vivo retinal ganglion cell axon regeneration after sharp optic nerve injury (1277 ± 180 regenerating retinal ganglion cells [n = 7] vs. 895 ± 164 regenerating retinal ganglion cells [n = 7], P = 0.005). Serial 80% N2O exposures reverses the benefit of folic acid on in vivo functional recovery after blunt spinal cord contusion (estimate for fixed effects ± standard error of the estimate: folic acid 5.60 ± 0.54 [n = 9] vs. folic acid + 80% N2O 5.19 ± 0.62 [n = 7], P < 0.0001).

Conclusions: These data indicate that nitrous oxide can impair the ability of central nervous system neurons to regenerate axons after sharp and blunt trauma.