Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K
Developmental Research Laboratories, Shionogi & Co., Ltd., Toyonaka, Japan.
Brain Res. 1996 Feb 19;709(2):296-302. doi: 10.1016/0006-8993(95)01324-5.
Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.
活化的中性粒细胞产生的氧自由基参与了缺血再灌注期间的脑损伤。血小板活化因子（PAF）是脑缺血再灌注期间中性粒细胞活化的介质之一。最近的证据表明，PAF诱导的中性粒细胞活化是由血栓素A2（TXA2）介导的。为了研究PAF和TXA2在脑缺血再灌注期间自由基产生中的作用，我们评估了PAF拮抗剂Y-24180和TXA2拮抗剂S-1452对大脑中动脉（MCA）闭塞1小时大鼠自由基形成的影响。在本研究中，我们采用了一种结合脑微透析的新电子自旋共振（ESR）方法。该方法使用内源性抗坏血酸自由基（AR）浓度作为氧自由基的标志物，不需要自旋捕获剂。在载体对照组中，缺血脑皮质的细胞外AR在MCA闭塞期间减少。再灌注后，AR在30分钟和1小时时显著增加，在2小时时恢复到接近基础水平，并在再灌注后24小时再次增加。在用S-1452或Y-24180治疗的大鼠中，AR在MCA闭塞期间减少的程度与载体对照组相同。然而，用Y-24180或S-1452预处理显著减弱了再灌注后细胞外AR的增加，而在整个实验期间对细胞外抗坏血酸或组织pO2的变化没有影响。总之，PAF和TXA2可能通过增加氧自由基的产生而导致脑缺血再灌注损伤。
