Yang Jing, Li Mengmeng, Hao Jiwei, Fang Xiaoyan, Zhang Qinghong, Tang Jiaguang, Hao Jianhua
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016 Mar;28(3):267-71.
To investigate effects of isoflurane anesthesia of different time interval on acute injury of brain function in neonatal rats with consistent total time of isoflurane anesthesia.
Seven-day neonatal Sprague-Dawley (SD) rats were randomly divided into normal control group (breathe the air), continuous anesthesia group (a single 6-hour exposure to 1.5% isoflurane), and intermittent anesthesia 1 day and 3 days groups (three times of 2-hour exposure to anesthesia with an interval of 1 day or 3 days), 12 rats in each group. The ratio of male to female was 5:7. They underwent the test of learning and memory in the radial arm maze (RAM) 21 days after birth, twice a day for 4 days. The number of entry into wrong arms, number of repeated errors, number of total arm entries, and time for completing the task were recorded for evaluation of effect of neonatal isoflurane on cognitive behavior in rats.
① Compared with normal control group, the percentage of number of errors > 3 in anesthesia of 3-day interval group was significantly decreased (33.3% vs. 46.9%, P < 0.05), the percentages of repeated errors > 0 and total arm entries > 8 were significantly increased (33.3% vs. 18.8%, 27.1% vs. 13.5%, both P < 0.05), but there were no statistically significant difference in the percentage of mistake number > 3 between continuous anesthesia group, interval anesthesia 1-day group and the normal control group (44.8%, 44.8% vs. 46.9%), the percentages of number of repeated mistake > 0 and total arm entries > 8 in above three groups were slightly increased as compared with those of normal control group (27.1%, 22.9% vs. 18.8%, 20.8%, 21.9% vs. 13.5%, all P > 0.05). No statistical differences in completing the task among normal control group, continuous anesthesia group, interval anesthesia 1 day and 3 days groups were found (minutes: 1.32±0.91, 1.54±1.05, 1.46±0.86, 1.38±0.79, all P > 0.05). ② It was found by gender analysis that the percentages number of repeated errors > 0 and total arm entries > 8 were significantly lower in female rats than those in the male rats only in normal control group (5.0% vs. 28.6%, P < 0.01; 5.0% vs. 19.6%, P < 0.05). There was no obvious gender difference in exposed groups. ③ Compared between groups of female rats, the percentages of repeated mistake > 0 in continuous anesthesia group, interval anesthesia 1 day and 3 days groups (25.0%, 25.0%, 30.0% vs. 5.0%, P < 0.05 or P < 0.01) and the percentage of total arm entries > 8 in interval anesthesia 1 day and 3 days groups were significantly higher than that of normal control group (22.5%, 25.0% vs. 5.0%, both P < 0.05). No significant difference about the RAM task in male rats of all the four groups was found.
Different time interval of neonatal isoflurane exposure may develop certain degree of acute brain injury in rats, characterized by cognitive function. Prolongation of the interval time significantly enhanced long-term memory in rats. Multiple neonatal exposures to isoflurane were associated with greater cognitive impairment than a single exposure. In addition, isoflurane can significantly increase cognitional functional disorder in the female, not in the male rats.
在异氟烷麻醉总时长一致的情况下，探讨不同时间间隔的异氟烷麻醉对新生大鼠脑功能急性损伤的影响。
将7日龄的新生Sprague-Dawley（SD）大鼠随机分为正常对照组（呼吸空气）、持续麻醉组（单次6小时暴露于1.5%异氟烷）、间歇麻醉1天组和间歇麻醉3天组（每次2小时麻醉暴露，间隔1天或3天），每组12只。雌雄比例为5:7。出生21天后，在放射状臂迷宫（RAM）中对它们进行学习和记忆测试，每天两次，共4天。记录进入错误臂的次数、重复错误次数、总臂进入次数和完成任务的时间，以评估新生大鼠异氟烷对认知行为的影响。
①与正常对照组相比，3天间隔麻醉组中错误次数>3的百分比显著降低（33.3%对46.9%，P<0.05），重复错误次数>0和总臂进入次数>8的百分比显著增加（33.3%对18.8%，27.1%对13.5%，均P<0.05），但持续麻醉组、间隔麻醉1天组与正常对照组之间错误次数>3的百分比无统计学差异（44.8%、44.8%对46.9%），上述三组中重复错误次数>0和总臂进入次数>8的百分比与正常对照组相比略有增加（27.1%、22.9%对18.8%，20.8%，21.9%对13.5%，均P>0.05）。正常对照组、持续麻醉组、间隔麻醉1天组和间隔麻醉3天组在完成任务方面无统计学差异（分钟：1.32±0.91，1.54±1.05，1.46±0.86，1.38±0.79，均P>0.05）。②通过性别分析发现，仅在正常对照组中，雌性大鼠重复错误次数>0和总臂进入次数>8的百分比显著低于雄性大鼠（5.0%对28.6%，P<0.01；5.0%对19.6%，P<0.05）。暴露组中无明显性别差异。③雌性大鼠组间比较，持续麻醉组、间隔麻醉1天组和间隔麻醉3天组中重复错误次数>0的百分比（25.0%，25.0%，30.0%对5.0%，P<0.05或P<0.01）以及间隔麻醉1天组和间隔麻醉3天组中总臂进入次数>8的百分比显著高于正常对照组（22.5%，25.0%对5.0%，均P<0.05）。四组雄性大鼠在RAM任务方面无显著差异。
新生大鼠异氟烷暴露的不同时间间隔可能会对大鼠造成一定程度的急性脑损伤，其特征为认知功能受损。间隔时间延长可显著增强大鼠的长期记忆。新生大鼠多次暴露于异氟烷比单次暴露导致的认知障碍更严重。此外，异氟烷可显著增加雌性而非雄性大鼠的认知功能障碍。
