Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent
Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent
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DOI：
10.1161/01.str.0000020092.41820.58
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发表时间：
2002-07-01
期刊：
影响因子：
8.3
通讯作者：
Dirnagl, U
中科院分区：
文献类型：
--
作者：
Kapinya, KJ;Löwl, D;Dirnagl, U
背景和目的-我们测试是否挥发性麻醉药诱导神经保护，是维持了一个延长的time. Methods-大鼠进行了预处理3小时，1最低麻醉浓度的异氟烷或氟烷在正常空气（麻醉预处理[AP]）。在AP后0、12、24或48小时，对动物进行永久性大脑中动脉闭塞（MCAO）。氟烷预处理的动物在AP后24小时进行MCAO。在MCAO后4天进行梗死体积的组织学评价。在AP后24小时用异氟醚测量脑葡萄糖利用率。将原代皮质神经元培养物暴露于1.4%异氟烷3小时。AP后24小时进行氧糖剥夺（OGD）。24小时后通过测量OGD后24小时释放到培养基中的乳酸脱氢酶来评估损伤。结果MCAO前0、12和24小时的异氟醚麻醉或MCAO前24小时的氟烷麻醉显著减少了梗死体积（分别为125 +/- 42 mm（3），P=0.024; 118 +/- 51 mm（3），P=0.008; 120 +/- 49 mm（3），P=0.009;和121 +/- 48 mm（3），P=0.018）与对照体积（180 +/- 51 mm（3））相比。大鼠3小时异氟烷麻醉对24小时后测量的局部或平均脑葡萄糖利用率没有任何影响。从AP处理的动物的皮质提取物的蛋白质印迹分析显示，诱导型NO合酶（iNOS）蛋白AP后6小时开始增加。iNOS抑制剂氨基胍（200 mg/kg IP）消除AP的梗死保留效应。在培养的皮层神经元，异氟烷暴露24小时OGD前减少OGD诱导的乳酸脱氢酶释放49%（P=0.002）。结论挥发性麻醉剂预处理诱导延长的神经保护在体外和体内，一个过程中，iNOS似乎是至关重要的参与。
Background and Purpose-We tested whether volatile anesthetics induce neuroprotection that is maintained for a prolonged time.Methods-Rats were pretreated for 3 hours with 1 minimal anesthetic concentration of isoflurane or halothane in normal air (anesthetic preconditioning [AP]). The animals were subjected to permanent middle cerebral artery occlusion (MCAO) at 0, 12, 24, or 48 hours after AP. Halothane-pretreated animals were subjected to MCAO 24 hours after AP. Histological evaluation of infarct volumes was performed 4 days after MCAO. Cerebral glucose utilization was measured 24 hours after AP with isoflurane. Primary cortical neuronal cultures were exposed to 1.4% isoflurane for 3 hours. Oxygen-glucose deprivation (OGD) was performed 24 hours after AP. Injury was assessed 24 hours later by measuring the release of lactate dehydrogenase into the medium 24 hours after OGD.Results-Isoflurane anesthesia at 0, 12, and 24 hours before MCAO or halothane anesthesia 24 hours before MCAO significantly reduced infarct volumes (125 +/- 42 mm(3), P=0.024; 118 +/- 51 mm(3), P=0.008; 120 +/- 49 mm(3), P=0.009; and 121 +/- 48 mm(3), P=0.018, respectively) compared with control volumes (180 +/- 51 mm(3)). Three hours of isoflurane anesthesia in rats did not have any effect on local or mean cerebral glucose utilization measured 24 hours later. Western blot analysis from cortical extracts of AP-treated animals revealed an increase of the inducible NO synthase (iNOS) protein beginning 6 hours after AP. The iNOS inhibitor aminoguanidine (200 mg/kg IP) eliminated the infarct-sparing effect of AP. In cultured cortical neurons, isoflurane exposure 24 hours before OGD decreased the OGD-induced release of lactate dehydrogenase by 49% (P=0.002).Conclusions-Pretreatment with volatile anesthetics induces prolonged neuroprotection in vitro and in vivo, a process in which iNOS seems to be critically involved.