Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats. (November 2019)

• Record Type: Journal Article
• Authors: Stewart, Krista J.; Iskandar, Bermans J.; Meier, Brenton M.; Rizk, Elias B.; Hariharan, Nithya; Koueik, Joyce; Andrei, Adin-Christian; Hogan, Kirk J.
• Is Part Of: Anesthesiology. Volume 131:Number 5(2019)
• Publication Date: 2019-11
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000002906
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : 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% N2 O 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% N2 O 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% N2 O 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% N2 O 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% N2 O 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. Abstract : 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.Supplemental Digital Content is available in the text.