BACKGROUND Our previous research showed that 4 h of maternal anesthesia with isoflurane during early gestation in pregnant rats leads to a deficit in spatial memory of adult male offspring. Because spatial memory is predominantly a hippocampally-mediated task, we asked the question if early gestational exposure to isoflurane affects development of the hippocampus in the offspring. FINDINGS Previously behaviorally characterized adult male rats that were exposed to isoflurane during second trimester were sacrificed at 4 months of age (N = 10 and 13, control and isoflurane groups, respectively) for quantitative histology of hippocampal subregions. Sections were stained with cresyl violet and the total number of cells in the granular layer of the dentate gyrus and the pyramidal cell layer in the CA1 region were determined by a blinded observer using unbiased stereological principles and the optical fractionator method. Data were analyzed using Student's t test; P < 0.05 was accorded statistical significance. Stereological examination revealed 9% fewer cells in the granular layer of the dentate gyrus of isoflurane-exposed adult rats compared to controls (1,002,122 ± 84,870 vs. 1,091,829 ± 65,791, respectively; Mean ± S.D, *P = 0.01). In contrast, there were no changes in the cell number in the CA1 region, nor were there changes in the volumes of both regions. CONCLUSIONS Our results show that maternal isoflurane anesthesia in rodents causes region-specific cell loss in the hippocampus of adult male offspring. These changes may, in part, account for the behavioral deficits reported in adult rats exposed to isoflurane in utero.

中文翻译：

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妊娠早期接触异氟烷会导致成年雄性大鼠的齿状回持续性细胞丢失。

背景技术我们先前的研究表明，怀孕大鼠在孕早期用异氟烷麻醉4 h会导致成年雄性后代的空间记忆不足。因为空间记忆主要是海马介导的任务，所以我们问了一个问题，即妊娠早期异氟烷的暴露是否会影响后代海马的发育。结果将先前具有行为特征的成年雄性大鼠在妊娠中期暴露于异氟烷时，在4个月大时（分别为N和10组，分别为对照组和异氟烷组）处死海马亚区，将其处死4个月。切片用甲酚紫染色，并由盲人使用无偏立体学原理和光学分馏器方法确定齿状回颗粒层和CA1区锥体细胞层的细胞总数。使用Student's t检验分析数据；P <0.05为具有统计学意义。体视学检查显示，与对照组相比，异氟烷成年大鼠的齿状回颗粒层中的细胞减少了9％（分别为1,002,122±84,870和1,091,829±65,791；平均值±SD，* P = 0.01）。相反，CA1区域的细胞数没有变化，两个区域的体积也没有变化。结论我们的结果表明，啮齿动物中的孕妇异氟烷麻醉会导致成年雄性后代海马的特定区域细胞丢失。这些变化可能部分解释了在子宫内暴露于异氟烷的成年大鼠中报告的行为缺陷。