Neuroprotective effects of lactate in brain ischemia: Dependence on anesthetic drugs

被引:59
作者
Horn, Tobias [1 ]
Klein, Jochen [1 ]
机构
[1] Goethe Univ Frankfurt, Coll Pharm, Dept Pharmacol, Bioctr, D-60438 Frankfurt, Germany
关键词
Isoflurane; Ketamine-xylazine; Lactate; Middle cerebral artery occlusion; Pentobarbital; CEREBRAL-ISCHEMIA; ENERGY SUBSTRATE; IN-VIVO; MICRODIALYSIS; MECHANISMS; RAT; METABOLISM; CORTEX;
D O I
10.1016/j.neuint.2012.12.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Lactate is a major energy source for the brain, especially when glucose is not available in sufficient amounts. In the present study, we administered sodium L-lactate (250 mg/kg) to mice before or after middle cerebral artery occlusion (MCAO) to test whether lactate can be neuroprotective in brain ischemia. Permanent ischemia for 24 h caused a large hemispheric lesion and a severe loss of body weight. Administration of lactate shortly (15-30 min) before MCAO strongly reduced cell death and weight loss, but only when isoflurane was used for anesthesia. Under pentobarbital anesthesia, lactate was inactive. After transient ischemia, when isoflurane or ketamine-xylazine were used as anesthetic drugs, lactate was effective when given immediately after reperfusion. In separate experiments, we found that plasma lactate levels are also strongly influenced by anesthetic drugs. Thus, isoflurane anesthesia as well as lactate administration caused strongly increased plasma levels of lactate whereas pentobarbital anesthesia significantly reduced plasma lactate. We conclude that exogenous lactate is neuroprotective in an in vivo-model of brain ischemia, but that its action is strongly influenced by the type of anesthetic agent used. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:251 / 257
页数:7
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