一氧化二氮抑制雄性大鼠神经系统损伤后的轴突再生。

Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats.

机构信息

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.) the Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (K.J.H.).

出版信息

Anesthesiology. 2019 Nov;131(5):1063-1076. doi: 10.1097/ALN.0000000000002906.

DOI:10.1097/ALN.0000000000002906

PMID:31490294

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% 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.

摘要

背景

一氧化二氮可诱导神经毒性。作者假设，接触一氧化二氮会损害中枢神经系统损伤后的轴突再生和功能恢复。

方法

在四种雄性大鼠中枢神经系统损伤模型中，测量单次和连续体内一氧化二氮暴露对轴突再生的影响：体内一氧化二氮给药后体外细胞培养中的轴突再生、尖锐性脊髓损伤后的体内轴突再生、尖锐性视神经损伤后的体内轴突再生和钝挫伤性脊髓损伤后的体内功能恢复。

结果

单次 70%N2O 体内暴露 48 小时后的体外轴突再生小于无一氧化二氮时的一半（平均值±SD，478±275μm；n=48），而 210±152μm（n=48；P<0.0001）。单次 80%N2O 暴露抑制叶酸对尖锐性脊髓损伤后体内轴突再生的有益作用（13.4±7.1%再生神经元[n=12]与 0.6±0.7%再生神经元[n=4]，P=0.004）。连续 80%N2O 给药逆转叶酸对尖锐性视神经损伤后体内视网膜神经节细胞轴突再生的益处（1277±180 再生的视网膜神经节细胞[n=7]与 895±164 再生的视网膜神经节细胞[n=7]，P=0.005）。连续 80%N2O 暴露逆转叶酸对钝挫伤性脊髓损伤后体内功能恢复的益处（固定效应的估计值±估计值的标准误差：叶酸 5.60±0.54[n=9]与叶酸+80%N2O 5.19±0.62[n=7]，P<0.0001）。