VEGF increases blood-brain barrier permeability to Evans blue dye and tetanus toxin fragment C but not adeno-associated virus in ALS mice
VEGF increases blood-brain barrier permeability to Evans blue dye and tetanus toxin fragment C but not adeno-associated virus in ALS mice
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DOI：
10.1016/j.brainres.2008.07.121
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发表时间：
2008-10-09
期刊：
影响因子：
2.9
通讯作者：
Brown, Robert H., Jr.
中科院分区：
文献类型：
--
作者：
Ay, Ilknur;Francis, Jonathan W.;Brown, Robert H., Jr.
大多数化合物进入CNS受到血脑屏障（BBB）的阻碍。由于血管内皮生长因子（VEGF）在BBB的形成和维持中是重要的，并且已知在新生啮齿动物中调节BBB渗透性，因此我们测试了VEGF可能增强成年小鼠BBB渗透性的假设。我们研究了VEGF对三种不同药物的CNS分布的影响：已知结合血浆蛋白的小分子（伊文思蓝染料）、外源性蛋白（破伤风毒素片段C; TTC）和病毒载体（用lacZ标记的重组腺相关病毒血清型2/5; rAAV 2/S-lacZ）。用VEGF（20 μ g; i.v.）BBB对伊文思蓝染料和TTC的渗透性增加，如通过大脑、脑干和脊髓中这些物质的浓度增加所检测到的。相比之下，VEGF不改变BBB对AAV 2/S-lacZ的渗透性，如通过β-半乳糖苷酶活性测定所定义的。这些数据证明了VEGF用于BBB的药理学调节的潜在效用，并且表明由VEGF介导的BBB渗透性的增加受到递送物质的大小的限制。(C)2008 Elsevier B. V.保留所有权利。
Entry of most compounds into the CNS is impeded by the blood-brain barrier (BBB). Because vascular endothelial growth factor (VEGF) is important in the formation and maintenance of the BBB and is known to modulate BBB permeability in newborn rodents, we tested the hypothesis that VEGF may enhance BBB permeability in adult mice. We examined the effect of VEGF on the CNS distribution of three different agents: a small molecule (Evans blue dye) that is known to bind plasma proteins, an exogenous protein (tetanus toxin fragment C; TTC), and a viral vector (recombinant adeno-associated virus serotype 2/5 marked with lacZ; rAAV2/S-lacZ). Pretreatment with VEGF (20 mu g; i.v.) increased permeability of the BBB to Evans blue dye and TTC as detected by augmented concentrations of these substances in the cerebrum, brainstem, and spinal cord. By contrast, VEGF did not alter BBB permeability to AAV2/S-lacZ, as defined by beta-galactosidase activity assay. These data demonstrate the potential utility of VEGF for pharmacological modulation of the BBB, and indicate that increase in BBB permeability mediated by VEGF is limited by the size of the delivered substance. (C) 2008 Elsevier B.V. All rights reserved.