Betz A L, Ren X D, Ennis S R, Hultquist D E
Department of Neurology, University of Michigan, Ann Arbor.
Acta Neurochir Suppl (Wien). 1994;60:314-7. doi: 10.1007/978-3-7091-9334-1_84.
Oxidized irwN has been proposed as a mediator of the free radical-induced damage that occurs during cerebral ischemia. Dihydroriboflavin, a compound produced from riboflavin (B2) by NADPH-dependent flavin reductase, rapidly reduces oxidized iron. Since treatment with riboflavin offers protection from ischemic injury in other tissues, we tested the effect of pretreatment with B2 on brain edema formation during focal ischemia. Two different models of middle cerebral artery occlusion (MCAO) in rats were tested: transcranial electrocautery and intracarotid occlusion with a nylon thread. Groups of 6-8 animals were treated with 7.5 mg of B2/kg or saline vehicle 1 h before MCAO and brain water content was determined after 4 h of ischemia. Pretreatment with B2 reduced total hemisphere edema formation from 0.37 +/- 0.05 to 0.19 +/- 0.05 mg/g dry wt. (48% protection, p < 0.01) following transcranial MCAO. Edema was greater following MCAO with the intra-carotid thread (0.54 +/- 0.05 ml/g) but protection by B2 was less (21%). We conclude that pretreatment with B2 reduces ischemic brain injury, perhaps by reacting with oxidized iron. However, the larger stroke produced by the thread MCAO method makes it more difficult to observe protection following brief ischemia in this model.
氧化型铁离子已被认为是脑缺血期间自由基诱导损伤的介质。二氢核黄素是由核黄素（B2）通过NADPH依赖性黄素还原酶产生的一种化合物，它能迅速还原氧化型铁离子。由于用核黄素治疗可使其他组织免受缺血性损伤，我们测试了用B2预处理对局灶性缺血期间脑水肿形成的影响。我们测试了大鼠大脑中动脉闭塞（MCAO）的两种不同模型：经颅电灼和用尼龙线进行颈内动脉闭塞。在MCAO前1小时，将6 - 8只动物分为一组，分别用7.5 mg/kg的B2或生理盐水处理，缺血4小时后测定脑含水量。经颅MCAO后，用B2预处理可使全脑半球水肿形成从0.37±0.05降至0.19±0.05 mg/g干重（保护率48%，p<0.01）。用颈内动脉线进行MCAO后的水肿更严重（0.54±0.05 ml/g），但B2的保护作用较小（21%）。我们得出结论，用B2预处理可减轻缺血性脑损伤，可能是通过与氧化型铁离子反应。然而，线栓法MCAO产生的较大梗死灶使得在该模型中短暂缺血后更难观察到保护作用。
