Zhao Ping, Peng Longyun, Li Liaoliao, Xu Xuebing, Zuo Zhiyi
Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, P.O. Box 800710, Charlottesville, Virginia 22908-0710, USA.
Anesthesiology. 2007 Dec;107(6):963-70. doi: 10.1097/01.anes.0000291447.21046.4d.
Preconditioning the brain with relatively safe drugs seems to be a viable option to reduce ischemic brain injury. The authors and others have shown that the volatile anesthetic isoflurane can precondition the brain against ischemia. Here, the authors determine whether isoflurane preconditioning improves long-term neurologic outcome after brain ischemia.
Six-day-old rats were exposed to 1.5% isoflurane for 30 min at 24 h before the brain hypoxia-ischemia that was induced by left common carotid arterial ligation and then exposure to 8% oxygen for 2 h. The neuropathology, motor coordination, and learning and memory functions were assayed 1 month after the brain ischemia. Western analysis was performed to quantify the expression of the heat shock protein 70, Bcl-2, and survivin 24 h after isoflurane exposure.
The mortality was 45% after brain hypoxia-ischemia. Isoflurane preconditioning did not affect this mortality. However, isoflurane preconditioning attenuated ischemia-induced loss of neurons and brain tissues, such as cerebral cortex and hippocampus in the survivors. Isoflurane also improved the motor coordination of rats at 1 month after ischemia. The learning and memory functions as measured by performance of Y-maze and social recognition tasks in the survivors were not affected by the brain hypoxia-ischemia or isoflurane preconditioning. The expression of Bcl-2, a well-known antiapoptotic protein, in the hippocampus is increased after isoflurane exposure. This increase was reduced by the inhibitors of inducible nitric oxide synthase. Inducible nitric oxide synthase inhibition also abolished isoflurane preconditioning-induced neuroprotection.
Isoflurane preconditioning improved the long-term neurologic outcome after brain ischemia. Inducible nitric oxide synthase may be involved in this neuroprotection.
使用相对安全的药物对大脑进行预处理似乎是减少缺血性脑损伤的一种可行选择。作者及其他研究人员已表明，挥发性麻醉药异氟烷能对大脑进行预处理以抵御缺血。在此，作者确定异氟烷预处理是否能改善脑缺血后的长期神经功能结局。
6日龄大鼠在左侧颈总动脉结扎诱导脑缺氧缺血前24小时，暴露于1.5%异氟烷中30分钟，随后暴露于8%氧气中2小时。在脑缺血1个月后测定神经病理学、运动协调性以及学习和记忆功能。在异氟烷暴露24小时后进行蛋白质免疫印迹分析以量化热休克蛋白70、Bcl-2和生存素的表达。
脑缺氧缺血后的死亡率为45%。异氟烷预处理未影响该死亡率。然而，异氟烷预处理减轻了幸存者中缺血诱导的神经元和脑组织（如大脑皮质和海马体）的损失。异氟烷还改善了缺血1个月后大鼠的运动协调性。幸存者中通过Y迷宫表现和社会识别任务测量的学习和记忆功能未受脑缺氧缺血或异氟烷预处理的影响。异氟烷暴露后，海马体中著名的抗凋亡蛋白Bcl-2的表达增加。诱导型一氧化氮合酶抑制剂可降低这种增加。抑制诱导型一氧化氮合酶也消除了异氟烷预处理诱导的神经保护作用。
异氟烷预处理改善了脑缺血后的长期神经功能结局。诱导型一氧化氮合酶可能参与了这种神经保护作用。
