An anesthetic regimen typically used during surgery on pregnant mothers appears to have a negative effect on the development of the fetus, according to a new study on mice conducted by neurobiologists from the National Center for Toxicological Research, in Arizona.
In the article 'Inhalation Anesthesia-Induced Neuronal Damage and Gene Expression Changes in Developing Rat Brain' published earlier this month in Systems Pharmacology, an open access journal by Versita -- Dr. Fang Liu and Dr. Cheng Wang describe the effect of major, commonly used anesthetic compounds -- Nitrous Oxide (N2O), N-methyl-D-aspartate (NMDA) receptor antagonist, and isoflurane (ISO) on the developing brain of post-natal rats. Looking into the mechanisms through which N2O + ISO cause neurotoxicity in the developing brain, the authors suggest multiple factors are involved in neuronal cell death inducing effects (cascades) of N2O + ISO.
As with any medical intervention performed during pregnancy, expectant mothers are concerned about the possibility of undergoing surgery or other medical procedures that require anesthesia and may be harmful to both the woman and her baby. Understandably, there is concern for the development of the fetus, but also for the immediate health of the mother and possible preterm labor. Until recently most studies of documented use have admittedly shown that inhaled anesthetics pose no risks for pregnant women.
Contrary to previous research findings, it has now emerged that the combination of N2O + ISO can change the gene expression of brain tissues and may be related to the elevated neuronal cell death as indicated by an increased number of apoptotic cells in frontal cortical levels compared with the control. The researchers came to this novel conclusion owing to the use of microarray data and cell analysis. They demonstrated that the combination of N2O + ISO induces a significant change in gene expression and cell death of neuronal tissues in post-natal rats. The brain tissue of post-natal rats seems to be more sensitive to N2O + ISO when compared to adult brains tissues.
Considering that pregnant women and neonates are subjected to anesthesia with N2O + ISO in determined clinical procedures, it could potentially affect the brain tissues of fetuses or neonates in long-term exposure to N2O + ISO.
"The findings come as a major step forward in better understanding of this phenomenon," says Prof. Diego Bonatto from the Department of Molecular Biology and Biotechnology at the Federal University of Rio Grande do Sul. A study in new-born rats published in 2003 indicated that exposure to various anesthetic agents caused neurodegeneration in the developing rat brain. In 2005 however, a more recent study on sheep carried out by researchers from Duke University Medical Center revealed that the moderate exposure to inhalation anesthetic during pregnancy is not harmful to the fetus.
This research deserves attention: for the first time the authors managed to show that the administration of N2O + ISO to neonates or pregnant women can potentially induce changes in molecular mechanisms associated to the cell survival, especially in brain tissue. Although the study will not change the current anesthesia procedure, there is enough data to suggest a potential effect of N2O + ISO to the brain tissues.
- Cheng Wang, William Slikker, Merle G. Paule, Joseph P. Hanig, Natalya Sadovova, Quan-Zhen Li, Tucker A. Patterson, Leming Shi, Shuo W. Rainosek, Jie Zhang, Lei Guo, Fang Liu. Inhalation Anesthesia-Induced Neuronal Damage and Gene Expression Changes in Developing Rat Brain. Systems Pharmacology, 2012; 1 (-1): 1 DOI: 10.2478/sph-2012-0001
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