Acute leakage patterns of fluorescent plasma flow markers after transient focal cerebral ischemia suggest large openings in blood-brain barrier
Acute leakage patterns of fluorescent plasma flow markers after transient focal cerebral ischemia suggest large openings in blood-brain barrier
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DOI：
10.1080/10739680701409811
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发表时间：
2008-01-01
期刊：
影响因子：
2.4
通讯作者：
Knight, Robert A.
中科院分区：
文献类型：
--
作者：
Nagaraja, Tavarekere N.;Keenan, Kelly A.;Knight, Robert A.
目的：本研究验证了急性再灌注期间血脑屏障（BBB）开放允许较小的大分子通过而不允许较大的大分子通过的假设，并且这种分子大小限制随着时间的推移而消失。Wistar大鼠（n = 42）在单侧大脑中动脉闭塞3小时（h）和再灌注3或21小时后，注射伊文思蓝（Evans blue（EB，一种荧光染料，其立即结合到血浆白蛋白，产生EB标记的白蛋白，EB-Alb），并且具有尺寸范围从77-至2000-kDa的三种荧光葡聚糖之一。在闭塞和再灌注过程中，通过磁共振成像（MRI）确认受影响组织的缺血状态。结果：再灌注3 ~ 21小时，EB-白蛋白渗漏量显著增加（占检查视野的40-60%~ 80-90%; p < 0.05）。在3+3 h时，仅在40%的视野中观察到使用的最大葡聚糖2000-kDa与EB-Alb的共渗漏，但在3 + 21 h时几乎在所有视野中观察到共渗漏（p < 0.01）。示踪剂的实质分布不同的领域之间，包括相当大的细胞摄取EB-白蛋白和一些dextrans.Conclusions：支持这一假设，开放的血脑屏障是不足以让最大的葡聚糖通过在3 + 3小时，在约40%的微血管网络。3 + 3 h和3 + 21 h之间总渗漏微血管床的数量增加了近50%。
Objective: This study tested the hypothesis that blood-brain barrier (BBB) opening during acute reperfusion permits the passage of smaller macromolecules but not larger ones and that this molecular size restriction disappears over time.Methods: Following 3 hours (h) of unilateral middle cerebral artery occlusion and either 3 or 21 h of reperfusion, Wistar rats (n = 42) were injected with Evans blue (EB, a fluorescent dye that binds instantly to plasma albumin yielding EB-tagged albumin, EB-Alb) and with one of three fluorescent dextrans ranging in size from 77- to 2000-kDa. During occlusion and reperfusion, ischemic status of the affected tissue was confirmed by magnetic resonance imaging (MRI). Blood-to-brain transfer of the dextrans relative to that of EB-Alb was examined by fluorescence microscopy within three regions with ischemic damage.Results: Increase in EB-Alb leakage from 3 to 21 h of reperfusion was significant (from 40-60% to 80-90% of fields examined; p < 0.05). Co-leakage of the largest dextran used 2000-kDa, with EB-Alb was observed in only 40% of the fields at 3+3 h, but nearly in all at 3 + 21 h (p < 0.01). Parenchymal distribution of the tracers differed among the fields and included considerable cellular uptake of EB-Alb and some of dextrans.Conclusions: Supporting the hypothesis, opening of the BBB was insufficient to allow passage of the largest dextran at 3 + 3 h in about 40% of the microvascular networks viewed. The number of total leaky microvascular beds increased by nearly 50% between 3 + 3 h and 3 + 21 h.