Department of Pharmacology, University of Melbourne and Melbourne Brain Centre, Carlton, Victoria, Australia.
Eur J Anaesthesiol. 2012 May;29(5):239-45. doi: 10.1097/EJA.0b013e32835103c1.
Postoperative cognitive dysfunction has been reported in young, middle-aged and elderly patients with greater incidence with increasing age. Neurocognitive deficits are associated with anaesthetic exposure in aged rodents but in younger adult animals the findings are inconsistent and in middle-aged animals they are unknown. We aimed to compare the effects of moderate duration isoflurane anaesthesia in 100% oxygen on Morris water maze performance in young adult and middle-aged rats. We hypothesised that isoflurane would have greater effects on learning and memory in middle-aged compared with young rats.
Young adult (3 months, n = 25) and middle-aged (12 months, n = 20) male Sprague Dawley rats were assigned randomly to isoflurane exposure (1 minimum alveolar concentration, 4 h) or control conditions. Spatial learning (acquisition phase) and memory (probe trial) were tested in the Morris water maze 1 week after exposure. Middle-aged rats were retested in the probe trial 4 weeks after exposure for long-term memory retention. Latency to locate the hidden platform and time spent in the platform quadrant were compared between ages and treatments.
Isoflurane did not affect acquisition of the water maze task in either age group. Isoflurane exposure induced a significant deficit in memory retention in young rats, but not middle-aged rats, in the probe trial 24 h after acquisition. Irrespective of treatment, middle-aged rats took longer to acquire the task than young rats. Four weeks after exposure, isoflurane-treated middle-aged rats showed no preference for target location, compared with sham-exposed rats which retained memory for previous platform location.
Isoflurane exposure impaired retention memory for platform location 1 week after exposure in young adult rats and resulted in a delayed although weak impairment at 4 weeks in middle-aged rats. The great variation in reported effects of isoflurane suggests a complex effect of this agent on memory which warrants further investigation.
术后认知功能障碍已在年轻、中年和老年患者中报道，且随年龄增长发病率增加。在老年啮齿动物中，神经认知缺陷与麻醉暴露有关，但在年轻成年动物中，研究结果不一致，在中年动物中则未知。我们旨在比较 100%氧气中中时效异氟醚麻醉对年轻成年和中年大鼠 Morris 水迷宫表现的影响。我们假设异氟醚对中年大鼠的学习和记忆的影响大于年轻大鼠。
将年轻成年（3 个月，n = 25）和中年（12 个月，n = 20）雄性 Sprague Dawley 大鼠随机分配至异氟醚暴露（1 个最小肺泡浓度，4 小时）或对照条件。暴露后 1 周，在 Morris 水迷宫中测试空间学习（获得阶段）和记忆（探针试验）。中年大鼠在暴露后 4 周的探针试验中进行长期记忆保留测试。比较年龄和处理之间的潜伏期以定位隐藏平台和在平台象限中花费的时间。
异氟醚在两个年龄组均未影响水迷宫任务的获得。异氟醚暴露在获得后 24 小时的探针试验中诱导年轻大鼠的记忆保留显著缺陷，但在中年大鼠中则没有。无论治疗如何，中年大鼠比年轻大鼠花费更长的时间来获得任务。暴露后 4 周，异氟醚处理的中年大鼠与未暴露的大鼠相比，对目标位置没有偏好，而未暴露的大鼠保留了对以前平台位置的记忆。
异氟醚暴露在年轻成年大鼠中损害了对平台位置的保留记忆，在 4 周后导致了延迟但较弱的损害。异氟醚对记忆的影响报告差异很大，这表明该药物对记忆有复杂的影响，需要进一步研究。
