McAuliffe John J, Loepke Andreas W, Miles Lili, Joseph Bernadin, Hughes Elizabeth, Vorhees Charles V
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3036, USA.
Anesthesiology. 2009 Sep;111(3):533-46. doi: 10.1097/ALN.0b013e3181b060d3.
The volatile anesthetics desflurane, isoflurane, and sevoflurane have been found to produce neuroprotection in various paradigms. The authors used these agents in a delayed preconditioning model to test the hypothesis that they could provide neuroprotection against neonatal hypoxia-ischemia as assessed by a battery of behavioral tests.
Institutional Animal Care and Use Committee approval was obtained. A total of 140, C57-129T2 F1 hybrid 9-day-old mice were randomized to 3 h of preconditioning with room air (Group Sham and Group HI), 8.4% desflurane in 40% oxygen (Group D), 1.8% isoflurane (Group I), or 3.1% sevoflurane (Group S). Twenty-four hours later, the Group HI, D, I, and S mice had 60 min of hypoxia-ischemia, and Group Sham had 60 min of sham HI. Surviving animals had behavioral testing, including open field activity, acoustic startle, prepulse inhibition, rotorod, novel object recognition, water mazes, and apomorphine challenge. Histologic analysis was also performed.
Mice in Groups D, I, and S performed better than Group HI and similarly to Group Sham on novel object recognition and apomorphine challenge and better than Group HI but not as well as Group Sham on cued maze testing. All mice exposed to hypoxia-ischemia performed worse than Group Sham on the spatially oriented water mazes with no difference among groups. Histologic sections did not show any significant effect of preconditioning on injury scores.
Volatile agent preconditioning partially protects perirhinal cortex and striatal dependent functions against moderate to severe neonatal hypoxia-ischemia.
已发现挥发性麻醉药地氟烷、异氟烷和七氟烷在各种模型中可产生神经保护作用。作者在延迟预处理模型中使用这些药物,以检验以下假设:通过一系列行为测试评估,它们可提供针对新生儿缺氧缺血的神经保护作用。
获得机构动物护理和使用委员会的批准。总共140只C57-129T2 F1杂交9日龄小鼠被随机分为用室内空气预处理3小时(假手术组和缺氧缺血组)、40%氧气中8.4%地氟烷(D组)、1.8%异氟烷(I组)或3.1%七氟烷(S组)。24小时后,缺氧缺血组、D组、I组和S组小鼠进行60分钟的缺氧缺血,假手术组进行60分钟的假缺氧缺血。存活的动物进行行为测试,包括旷场活动、听觉惊吓、前脉冲抑制、转棒试验、新物体识别、水迷宫和阿扑吗啡激发试验。还进行了组织学分析。
在新物体识别和阿扑吗啡激发试验中,D组、I组和S组小鼠的表现优于缺氧缺血组,与假手术组相似;在提示性迷宫测试中,D组、I组和S组小鼠的表现优于缺氧缺血组,但不如假手术组。在空间定向水迷宫中,所有暴露于缺氧缺血的小鼠表现均比假手术组差,各组之间无差异。组织学切片未显示预处理对损伤评分有任何显著影响。
挥发性药物预处理可部分保护鼻周皮质和纹状体依赖性功能免受中度至重度新生儿缺氧缺血的影响。