Department of Medical Biochemistry and Global COE, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Brain Res. 2010 Mar 19;1321:164-8. doi: 10.1016/j.brainres.2010.01.039. Epub 2010 Jan 21.
Ischemia-reperfusion injury is induced by recovery of blood flow after ischemia. This phenomenon is a main cause of ischemic brain injury. The integrity of the blood-brain barrier (BBB) fails after cerebral ischemia and reperfusion. Further elucidation of this phenomenon promotes to develop treatment strategies for ischemia-reperfusion injury. In the present study, we attempted to examine the time-dependent change of ischemia-reperfusion injury in relation to BBB disorders at acute phase in a transient middle cerebral artery occlusion (t-MCAO) model rat as a cerebral infarction and reperfusion model. Brain cell damage after the reperfusion was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. To clarify a time-dependent change of the integrity of BBB, fluorescein isothiocyanate (FITC)-dextran (150 kDa) was injected intravenously into t-MCAO rats, and time-dependent localization of FITC-dextran was monitored in ex vivo. As a result, obvious brain damage was firstly observed at 3 h after reperfusion following 1 h of MCAO. In contrast, the leakage of FITC-dextran from cerebral vessels was observed immediately after the reperfusion. The present data suggest that the integrity of BBB failed prior to the occurrence of serious brain damage induced by ischemia-reperfusion, and that macromolecules such as water-soluble polymers and proteins which cannot pass through the BBB under normal condition would reach brain parenchyma at early stage after reperfusion. These findings would be useful to establish a novel treatment strategy for reperfusion injury after cerebral infarction.
缺血再灌注损伤是由缺血后血流恢复引起的。这种现象是缺血性脑损伤的主要原因。脑缺血再灌注后血脑屏障（BBB）的完整性丧失。进一步阐明这一现象有助于开发缺血再灌注损伤的治疗策略。在本研究中，我们试图在短暂性大脑中动脉闭塞（t-MCAO）模型大鼠作为脑梗死和再灌注模型中，检查与急性相 BBB 紊乱相关的缺血再灌注损伤的时间依赖性变化。通过 2,3,5-三苯基氯化四氮唑（TTC）染色评估再灌注后脑细胞损伤。为了阐明 BBB 完整性的时间依赖性变化，将异硫氰酸荧光素（FITC）-葡聚糖（150 kDa）静脉内注射到 t-MCAO 大鼠中，并在体监测 FITC-葡聚糖的时间依赖性定位。结果，在 MCAO 后 1 小时再灌注后 3 小时首次观察到明显的脑损伤。相比之下，在再灌注后立即观察到 FITC-葡聚糖从脑血管漏出。本数据表明，在缺血再灌注引起的严重脑损伤发生之前，BBB 的完整性已经丧失，并且在再灌注后早期，正常情况下无法通过 BBB 的水溶性聚合物和蛋白质等大分子物质会到达脑实质。这些发现将有助于为脑梗死再灌注损伤建立新的治疗策略。
