Bickler P E, Buck L T, Feiner J R
Department of Anesthesia, University of California School of Medicine, San Francisco 94143-0542, USA.
Anesthesiology. 1995 Dec;83(6):1233-40. doi: 10.1097/00000542-199512000-00014.
Extracellular accumulation of the excitatory neurotransmitter L-glutamate during cerebral hypoxia or ischemia contributes to neuronal death. Anesthetics inhibit release of synaptic neurotransmitters but it is unknown if they alter net extrasynaptic glutamate release, which accounts for most of the glutamate released during hypoxia or ischemia. The purpose of this study was to determine if different types of anesthetics decrease hypoxia-induced glutamate release from rat brain slices.
Glutamate released from cortical brain slices was measured fluorometrically with the glutamate dehydrogenase catalyzed formation of the reduced form of nicotinamide adenine dinucleotide phosphate. Glutamate release was measured in oxygenated (PO2 = 400 mmHg), hypoxic ((PO2 = 20 mmHg), and anoxic ((PO2 = 20 mmHg plus 100 microM NaCN) solutions and with clinical concentrations of anesthetics (halothane 325 microM, enflurane 680 microM, propofol 200 microM, sodium thiopental 50 microM). The source of glutamate released during these stresses was defined with toxins inhibiting N and P type voltage-gated calcium channels, and with calcium-free medium.
Glutamate released during hypoxia or anoxia was 1.5 and 5.3 times greater, respectively, than that evoked by depolarization with 30 mM KCl. Hypoxia/anoxia-induced glutamate release was not mediated by synaptic voltage-gated calcium channels, but probably by the reversal of normal uptake mechanisms. Halothane, enflurane, and sodium thiopental, but not propofol, decreased hypoxia-evoked glutamate release by 50-70% (P < 0.05). None of the anesthetics alter basal glutamate release.
The authors conclude that halothane, enflurane, and sodium thiopental but not propofol, at clinical concentrations, decrease extrasynaptic release of L-glutamate during hypoxic stress.
在脑缺氧或缺血期间，兴奋性神经递质L-谷氨酸在细胞外的蓄积会导致神经元死亡。麻醉剂可抑制突触神经递质的释放，但它们是否会改变突触外谷氨酸的净释放尚不清楚，而突触外谷氨酸的释放占缺氧或缺血期间释放的谷氨酸的大部分。本研究的目的是确定不同类型的麻醉剂是否会减少缺氧诱导的大鼠脑片谷氨酸释放。
用谷氨酸脱氢酶催化烟酰胺腺嘌呤二核苷酸磷酸还原形式的形成，通过荧光法测量从皮质脑片释放的谷氨酸。在含氧（PO2 = 400 mmHg）、缺氧（PO2 = 20 mmHg）和无氧（PO2 = 20 mmHg加100 μM NaCN）溶液中，以及在临床浓度的麻醉剂（氟烷325 μM、恩氟烷680 μM、丙泊酚200 μM、硫喷妥钠50 μM）存在的情况下测量谷氨酸释放。用抑制N型和P型电压门控钙通道的毒素以及无钙培养基确定这些应激期间释放的谷氨酸的来源。
缺氧或无氧期间释放的谷氨酸分别比用30 mM KCl去极化诱发的谷氨酸高1.5倍和5.3倍。缺氧/无氧诱导的谷氨酸释放不是由突触电压门控钙通道介导的，可能是由正常摄取机制的逆转介导的。氟烷、恩氟烷和硫喷妥钠，但不是丙泊酚，使缺氧诱发的谷氨酸释放减少了50 - 70%（P < 0.05）。没有一种麻醉剂改变基础谷氨酸释放。
作者得出结论，在临床浓度下，氟烷、恩氟烷和硫喷妥钠，但不是丙泊酚，会减少缺氧应激期间L-谷氨酸的突触外释放。
