Accumulation of macromolecules in brain parenchyma in acute phase of cerebral infarction/reperfusion
Accumulation of macromolecules in brain parenchyma in acute phase of cerebral infarction/reperfusion
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DOI：
10.1016/j.brainres.2010.01.039
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发表时间：
2010-03-19
期刊：
影响因子：
2.9
通讯作者：
Oku, Naoto
中科院分区：
文献类型：
--
作者：
Ishii, Takayuki;Asai, Tomohiro;Oku, Naoto
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）的完整性下降。对这一现象的进一步阐明有助于制定缺血再灌注损伤的治疗策略。在本研究中，我们试图研究缺血-再灌注损伤的时间依赖性变化与血脑屏障障碍在急性期在短暂的大脑中动脉闭塞（t-MCAO）模型大鼠作为脑梗死和再灌注模型。再灌注后通过氯化三苯四氮唑（TTC）染色评估脑细胞损伤。为了阐明血脑屏障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，并在体外监测FITC-葡聚糖的时间依赖性定位。结果表明，MCAO 1h后再灌注3 h即出现明显的脑损伤。相反，在再灌注后立即观察到FITC-葡聚糖从脑血管中渗漏。提示在缺血再灌注引起严重脑损伤之前，血脑屏障的完整性已经丧失，而在正常情况下不能通过血脑屏障的水溶性聚合物和蛋白质等大分子物质在再灌注后早期就能到达脑实质。这些发现将有助于建立一种新的治疗策略，脑梗死后再灌注损伤。(C)2010爱思唯尔有限公司版权所有。
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. (C) 2010 Elsevier B.V. All rights reserved.