Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults.
Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults.
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DOI：
10.1097/aln.0b013e318209aa71
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发表时间：
2011-03
期刊：
影响因子：
8.8
通讯作者：
Culley DJ
中科院分区：
文献类型：
--
作者：
Palanisamy A;Baxter MG;Keel PK;Xie Z;Crosby G;Culley DJ
临床前证据表明，常用的麻醉剂在生命早期给药时会诱导持久的神经行为变化，但几乎没有人关注母体麻醉对胎儿神经发育的影响。本研究检验了以下假设：在妊娠第14天（相当于人类妊娠中期）母体麻醉期间暴露于异氟烷的胎鼠在成年后会出现行为异常。定时的妊娠大鼠在妊娠第14天随机分配接受1.4%异氟烷的100%氧气（N = 3）或100%氧气（N = 2）4小时。从8周龄开始，评价雄性后代的自发运动活动、海马依赖性学习和记忆（自发交替、新物体识别和径向臂迷宫）以及焦虑（高架十字迷宫）。母兽对异氟烷麻醉的生理耐受性良好。出生前暴露于异氟烷的成年大鼠在自发运动活动、自发交替或物体识别记忆方面与对照组无差异，但在高架十字迷宫上进入更多的开放臂，在桡臂迷宫上花费更长时间并犯更多的遗漏错误。与对照组相比，在子宫内暴露于异氟烷的大鼠（时间相当于人类妊娠中期）的空间记忆获得受损，焦虑减轻。这表明母体麻醉可能对胎儿大脑产生不利影响，并提出了异氟烷有害神经发育影响的脆弱性在生命中比以前认识到的更早开始的可能性。
Preclinical evidence suggests that commonly used anesthetic agents induce long-lasting neurobehavioral changes when administered early in life but there has been virtually no attention to the neurodevelopmental consequences for the fetus of maternal anesthesia. This study tested the hypothesis that fetal rats exposed to isoflurane during maternal anesthesia on gestational day 14, which corresponds to the second trimester in humans, would be behaviorally abnormal as adults. Timed, pregnant rats were randomly assigned on gestational day 14 to receive 1.4% isoflurane in 100% oxygen (N = 3) or 100 % oxygen (N = 2) for 4 h. Beginning at 8 weeks of age, male offspring were evaluated for spontaneous locomotor activity, hippocampal dependent learning and memory (spontaneous alternations, novel object recognition, and radial arm maze), and anxiety (elevated plus maze). Isoflurane anesthesia was physiologically well tolerated by the dams. Adult rats exposed prenatally to isoflurane were not different than controls on spontaneous locomotor activity, spontaneous alternations, or object recognition memory but made more open arm entries on the elevated plus maze and took longer and made more errors of omission on the radial arm maze. Rats exposed to isoflurane in utero at a time that corresponds to the second trimester in humans have impaired spatial memory acquisition and, reduced anxiety compared to controls. This suggests the fetal brain may be adversely affected by maternal anesthesia and raises the possibility that vulnerability to deleterious neurodevelopmental effects of isoflurane begins much earlier in life than previously recognized.