Lee Bradley H, Chan John Thomas, Kraeva Ekaterina, Peterson Katherine, Sall Jeffrey W
Department of Anesthesia and Perioperative Care, University of California, San Francisco, 513 Parnassus Ave., Box 0542, Med Sci S261, San Francisco, CA 94143, USA.
University of Arizona College of Medicine, 550 E Van Buren St., Phoenix, AZ 85004, USA.
Neuropharmacology. 2014 Aug;83:9-17. doi: 10.1016/j.neuropharm.2014.03.011. Epub 2014 Apr 1.
Volatile anesthetics are used widely for achieving a state of unconsciousness, yet these agents are incompletely understood in their mechanisms of action and effects on neural development. There is mounting evidence that children exposed to anesthetic agents sustain lasting effects on learning and memory. The explanation for these behavioral changes remains elusive, although acute neuronal death after anesthesia is commonly believed to be a principal cause. Rodent models have shown that isoflurane exposure in newborns induces acute neuroapoptosis and long-term cognitive impairment. However, the assessment of predisposing factors is lacking. We investigated the role of sex by delivering isoflurane to postnatal day (P)7 male and female Sprague Dawley rats for 4 h. Brain cell death was assessed 12 h later using FluoroJade C staining in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. Behavior was assessed separately using a series of object recognition tasks and a test of social memory beginning at P38. We found that isoflurane exposure significantly increased neuronal death in each brain region with no difference between sexes. Behavioral outcome was also equivalent in simple novel object recognition. However, only males were impaired in the recognition of objects in different locations and contexts. Males also exhibited deficient social memory while females were intact. The profound behavioral impairment in males relative to females, in spite of comparable cell death, suggests that males are more susceptible to long-term cognitive effects and this outcome may not be exclusively attributed to neuronal death.
挥发性麻醉剂被广泛用于诱导意识丧失状态，然而这些药物的作用机制及其对神经发育的影响尚未完全明确。越来越多的证据表明，接触麻醉剂的儿童会对学习和记忆产生持久影响。尽管通常认为麻醉后急性神经元死亡是主要原因，但这些行为变化的原因仍不明确。啮齿动物模型显示，新生动物接触异氟烷会诱导急性神经细胞凋亡和长期认知障碍。然而，目前缺乏对易感因素的评估。我们通过给出生后第7天（P7）的雄性和雌性Sprague Dawley大鼠吸入异氟烷4小时来研究性别因素的作用。12小时后，使用FluoroJade C染色法评估丘脑、海马体CA1-3区和齿状回的脑细胞死亡情况。从P38开始，分别使用一系列物体识别任务和社交记忆测试来评估行为。我们发现，接触异氟烷会显著增加每个脑区的神经元死亡，且两性之间无差异。在简单的新物体识别中，行为结果也相当。然而，只有雄性在识别不同位置和情境中的物体时受损。雄性还表现出社交记忆缺陷，而雌性则正常。尽管细胞死亡情况相当，但雄性相对于雌性存在严重的行为损伤，这表明雄性更容易受到长期认知影响，而且这种结果可能不完全归因于神经元死亡。
