Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain
Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain
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DOI：
10.1016/j.neuroscience.2003.07.012
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Olney, JW
中科院分区：
文献类型：
--
作者：
Jevtovic-Todorovic, V;Beals, J;Olney, JW
吸入麻醉剂和N-甲基-D-天冬氨酸(NMDA)拮抗剂一氧化二氮(N2O)短期暴露于成年大鼠后扣带回/脾后皮质(PC/RSC)神经元，可引起可逆性神经毒性空泡反应，与其他低剂量NMDA拮抗剂引起的反应相似。由于高剂量或长时间暴露于其他NMDA拮抗剂可导致神经元死亡，我们评估了长时间暴露N2O是否也可能导致神经细胞死亡。将成年雌性SD大鼠暴露于150%N2O(对大鼠的N2O麻醉的EC50约为50)中，研究了可逆空泡反应开始和消失的时间进程以及引发细胞死亡的时间进程和剂量要求。150%N2O暴露3h后，PC/RSC神经元的空泡反应最强，较长时间的N2O暴露后即可观察到相同程度的空泡反应。3h终止N2O，1h后处死大鼠，空泡反应明显减弱，3h后处死大鼠，空泡反应完全消失。长期暴露于150%N2O(8h或更长时间)可引起神经细胞死亡，32h后银染可见神经元死亡。同时给予GABA能药物地西潘(静脉注射)。我们的研究结果表明，成年大鼠短期暴露于N2O会对PC/RSC神经元造成迅速可逆的损伤，而长期暴露于N2O会导致神经细胞死亡。这些神经毒性效应，包括细胞死亡反应，可以通过联合使用GABA类麻醉剂来预防。NMDA受体阻断的时间似乎是神经元是否受到可逆性损伤或被NMDA拮抗剂药物驱动而导致细胞死亡的重要决定因素。(C)2003年IBRO。爱思唯尔有限公司出版。保留所有权利。
Short-term exposure of adult rats to nitrous oxide (N2O), an inhalational anesthetic and NMDA (N-methyl-D-aspartate) antagonist, causes a reversible neurotoxic vacuole reaction in neurons of the posterior cingulate/retrosplenial cortex (PC/RSC) which resembles that caused by low doses of other NMDA antagonists. Since high doses or prolonged exposure to other NMDA antagonists can cause neurons to die, we assessed whether prolonged N2O exposure might also cause neuronal cell death. Adult female Sprague-Dawley rats were exposed to 150-vol% N2O (approximately EC50 for N2O anesthesia in rats) for various durations from I to 16 h. The time course for onset and disappearance of the reversible vacuole reaction was studied, as was the time course and dose requirement for triggering cell death. A maximum vacuole reaction was observed in PC/RSC neurons in brains examined immediately after 3 h of 150-vol% N2O exposure and the same magnitude of vacuole reaction was observed when brains were examined immediately after a longer period of N2O exposure. When N2O was terminated at 3 h and the rats were killed 1 h later, the vacuole reaction was markedly diminished and if the rats were killed 3 h later the vacuole reaction had completely disappeared. Prolonged exposure to 150-vol% N2O (for 8 h or more) caused neuronal cell death which was detectable by silver staining 32 h later. Concurrently administered GABAergic agents, diazepam (an i.v. anesthetic), or isoflurane (an inhalational anesthetic), prevented this cell death reaction.Our findings demonstrate that short-term exposure of adult rats to N2O causes injury to PC/RSC neurons that is rapidly reversible, and prolonged N2O exposure causes neuronal cell death. These neurotoxic effects, including the cell death reaction, can be prevented by coadministration of GABAmimetic anesthetic agents. Duration of NMDA receptor blockade appears to be an important determinant of whether neurons are reversibly injured or are driven to cell death by an NMDA antagonist drug. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.