Cell Proliferation in Developing Brain after Brief Exposure to Nitrous Oxide or Halothane

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Abstract
Several inhalant anesthetics, including nitrous oxide and halothane, are known to be antimitotic in a variety of developing tissues, but none has been tested for antimitotic activity in developing brain. Concern about the safety of these agents has centered around behavioral effects reported in humans and animals after early exposure. Because interference with cell production during CNS development is a sufficient cause for later behavioral abnormalities, it is important to known whether cell production in the nervous system is altered by these agents. Mice were exposed to either nitrous oxide (75% N2O and 25% O2) or halothane (0.5% halothane in 75% N2 and 25% O2) or a mixture of 75% N2 and 25% O2. Prenatal treatment groups were exposed for 6 h on the 14th day of gestation, while postnatal treatment groups were exposed for 4 h on the second day after birth. Treated and control animals were then killed immediately after exposure, or 12, 24, or 48 h later, to be evaluated for CNS mitotic activity. Each of the four anesthetic-exposed groups showed some deviations from normal mitosis, but only the postnatal nitrous oxide group showed the pattern of reduced cell proliferation followed by a rebound that is characteristic of many antimitotic teratogens. Although prenatal nitrous oxides'' effects on the fetal brain wre not clearly interpretable, it did delay development of blood, as has been reported by other investigators. Both nitrous oxide and halothane significantly reduced body weight of fetuses in utero, but did not reduce body weight of neonates. The pattern of the body-weight effects suggests that they occur by some mechanism other than reduced cell production. The results indicate that nitrous oxide and halothane disrupt development in several ways, but are not antimitotic in all tissues at all times. Nitrous oxide does appear to be antimitotic to the late-forming cells of the cerebellar cortex.