Isoflurane reduces N-methyl-D-aspartate toxicity in vivo in the rat cerebral cortex
Isoflurane reduces N-methyl-D-aspartate toxicity in vivo in the rat cerebral cortex
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DOI：
10.1097/00000539-199912000-00022
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发表时间：
1999-12-01
影响因子：
5.7
通讯作者：
Patel, PM
中科院分区：
文献类型：
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作者：
Harada, H;Kelly, PJ;Patel, PM
最近的体外数据表明，异氟烷可降低N-甲基-D-天冬氨酸（NMDA）受体介导的反应，从而可能降低兴奋性毒性。然而，异氟烷对体外NMDA受体介导的毒性的影响尚不清楚。我们进行了本研究，以评估异氟醚对损伤产生的皮层注射NMDA在体内，并比较它与地佐环平，NMDA受体拮抗剂。用异氟烷麻醉禁食的Wistar-Kyoto大鼠。将NMDA 50 nmole（5 μ L体积）立体定向注射到四组之一动物的皮质2.8 mm外侧和（2.8 mm吻侧前囟，深度2 mm）。在异氟烷组中，异氟烷的潮气末浓度维持在脑电图（EEG）-爆发抑制（BS）剂量（2.2%-2.3%，n = 12）或1个最小肺泡麻醉浓度（MAC）剂量（n = 10）。地佐环平组（n = 10）在注射NMDA前15 min静脉注射地佐环平10 mg/kg。在清醒组和地佐环平组中，在完成NMDA注射后停止麻醉，并允许动物清醒。对照组（n = 10）皮质内注入人工脑脊液20 μ L。在NMDA注射后2天评价对皮质的损伤。Tn 1 MAC剂量;与清醒状态相比，在EEG-BS剂量下，异氟烷减少了皮层NMDA注射产生的损伤（1.74 +/- 0.49和0.96 +/- 0.46 vs 2.34 +/- 0.56 mm（3）; P = 0.02）。与清醒状态相比，地佐环平减少了皮质损伤（0.56 +/- 0.27; P = 0.01）。对照组的损伤仅限于插管插入造成的创伤。异氟醚EEG-BS组和地佐环平组与对照组相比，损伤程度无明显差异。意义：异氟烷可剂量依赖性地减轻N-甲基-D-天冬氨酸介导的皮质损伤。这些数据与先前证明的异氟烷降低N-甲基-D-天冬氨酸受体介导的体外反应的能力一致。
Recent in vitro data indicate that isoflurane can reduce N-methlyl-D-aspartate (NMDA) receptor-mediated responses and thereby might reduce excitotoxicity. However, the effect of isoflurane on NMDA receptor-mediated toxicity in vitro is not known. We conducted the present study to evaluate the effect of isoflurane on injury produced by cortical injection of NMDA in vivo and to compare it with dizocilpine, an antagonist of the NMDA receptor. Fasted Wistar-Kyoto rats were anesthetized with isoflurane. NMDA 50 nmoles (5-mu L volume) were stereotactically injected into the cortex 2.8 mm lateral and (2.8 mm rostral to the bregma, depth 2 mm) of animals in one of four groups. In the isoflurane groups, the end-tidal concentration of isoflurane was maintained at either electroencephalogram (EEG)-burst suppression (BS) doses (2.2%-2.3%, n = 12) or a 1 minimum alveolar anesthetic concentration (MAC) dose (n = 10). In the dizocilpine group (n = 10), 10 mg/kg dizocilpine was injected IV 15 min before the NMDA injection. In the awake group and the dizocilpine group, anesthesia was discontinued on completion of the NMDA injection, and the animals were allowed to awaken. In the animals in the control group (n = 10), 20 mu L of artificial cerebrospinal fluid was injected into the cortex. Injury to the cortex was evaluated 2 days after the NMDA injection. Tn 1 MAC doses;nd EEG-BS doses, isoflurane reduced the injury produced by a cortical NMDA injection compared with the awake state (1.74 +/- 0.49 and 0.96 +/- 0.46 vs 2.34 +/- 0.56 mm(3); P = 0.02). Dizocilpine reduced cortical injury (0.56 +/- 0.27; P = 0.01) compared with the awake state. Injury in the control group was limited to the trauma produced by cannula insertion. In the isoflurane EEG-BS and dizocilpine groups, the injury was not different from, the control group. Implications: Isoflurane can reduce N-methyl-D-aspartate-mediated cortical injury in vivo in a dose-dependent manner. These data are consistent with the previously demonstrated ability of isoflurane to reduce N-methyl-D-aspartate receptor-mediated responses in vitro.