Background

Studies in developing animals show that a clinically relevant anaesthesia exposure increases neuronal death and alters brain structure. In the hippocampal dentate gyrus, the anaesthetic isoflurane induces selective apoptosis among roughly 10% of 2-week-old hippocampal granule cells in 21-day-old mice. In this work, we queried whether the 90% of granule cells surviving the exposure might be ‘injured’ and integrate abnormally into the brain.

Methods

The long-term impact of isoflurane exposure on granule cell structure was studied using a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Male and female mice were exposed to isoflurane for 6 h when the fate-mapped granule cells were 2 weeks old. The morphology of the fate-mapped granule cells was quantified 2 months later.

Results

The gross structure of the dentate gyrus was not affected by isoflurane treatment, with granule cells present in the correct subregions. Individual isoflurane-exposed granule cells were structurally normal, exhibiting no changes in spine density, spine type, dendrite length, or presynaptic axon terminal structure (P>0.05). Granule cell axon terminals were 13% larger in female mice relative to males; however, this difference was evident regardless of treatment (difference of means=0.955; 95% confidence interval, 0.37–1.5; P=0.010).

Conclusions

A single, prolonged isoflurane exposure did not impair integration of this age-specific cohort of granule cells, regardless of the animal's sex. Nonetheless, although 2-week-old cells were not affected, the results should not be extrapolated to other age cohorts, which may respond differently.

中文翻译：

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一次异氟烷暴露后，未成熟的鼠海马神经元不会形成长期的结构变化

背景

对发育中的动物的研究表明，与临床相关的麻醉剂暴露会增加神经元死亡并改变大脑结构。在海马齿状回中，麻醉异氟烷在21日龄小鼠中约10％的2周龄海马颗粒细胞中诱导选择性凋亡。在这项工作中，我们询问幸免于暴露的90％颗粒细胞是否可能被“伤害”并异常整合到大脑中。

方法

异氟烷暴露对颗粒细胞结构的长期影响是使用转基因小鼠模型命运映射法鉴定和标记未成熟的颗粒细胞而研究的。当命运映射的颗粒细胞为2周龄时，将雄性和雌性小鼠暴露于异氟烷6小时。2个月后对命运映射的颗粒细胞的形态进行了定量。

结果

齿状回的总体结构不受异氟烷处理的影响，颗粒细胞存在于正确的子区域。单个异氟烷暴露的颗粒细胞在结构上是正常的，脊柱密度，脊柱类型，树突长度或突触前轴突末端结构没有变化（P > 0.05）。雌性小鼠的颗粒细胞轴突末端比雄性大13％。然而，无论采用何种治疗方法，这种差异都是显而易见的（均数差异= 0.955； 95％置信区间为0.37-1.5；P = 0.010）。

结论

不论动物的性别如何，一次长时间的异氟烷暴露都不会损害该特定年龄组的颗粒细胞的整合。虽然如此，尽管2周龄的细胞没有受到影响，但结果不应外推至其他年龄段的人群，这可能会有不同的反应。