VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain
VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain
复制标题
DOI：
10.1172/jci9369
复制
发表时间：
2000-10-01
影响因子：
15.9
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Zhang, ZG;Zhang, L;Chopp, M
VEGF是一种与血管生成相关的分泌型有丝分裂原，也是一种有效的血管通透性因子。VEGF在缺血性脑中的生物学作用仍然未知。本研究旨在探讨VEGF是否增强脑微血管灌注和增加缺血脑中血脑屏障（BBB）渗漏。利用磁共振成像（MRI）、三维激光扫描共聚焦显微镜和功能神经学测试，我们观察了给予重组人VEGF（165）（rhVEGF（165））对局灶性脑栓塞性缺血大鼠模型血管生成、功能神经学结果和BBB渗漏的影响。对缺血大鼠晚期（48小时）给予rhVEGF（165）增强了缺血半暗带的血管生成，并显著改善了神经恢复。然而，缺血后早期（1小时）给予缺血大鼠rhVEGF（165）显著增加了BBB渗漏、出血性转化和缺血性病变。rhVEGF（165）对缺血大鼠对侧脑血脑屏障通透性和脑血浆灌注无明显影响。我们的研究结果表明，VEGF可以显着增强缺血性脑血管生成，减少中风恢复过程中的神经功能缺损，在中风的急性期抑制VEGF可能会降低BBB通透性和局灶性脑缺血后出血性转化的风险。
VEGF is a secreted mitogen associated with angiogenesis and is also a potent vascular permeability factor. The biological role of VEGF in the ischemic brain remains unknown. This study was undertaken to investigate whether VEGF enhances cerebral microvascular perfusion and increases blood-brain barrier (BBB) leakage in the ischemic brain. Using magnetic resonance imaging (MRI), three-dimensional laser-scanning confocal microscope, and functional neurological tests, we measured the effects of administrating recombinant human VEGF(165) (rhVEGF(165)) On angiogenesis, functional neurological outcome, and BBB leakage in a rat model of focal cerebral embolic ischemia. Late (48 hours) administration of rhVEGF(165) to the ischemic rats enhanced angiogenesis in the ischemic penumbra and significantly improved neurological recovery. However, early postischemic (1 hour) administration of rhVEGF(165) to ischemic rats significantly increased BBB leakage, hemorrhagic transformation, and ischemic lesions. Administration of rhVEGF(165) to ischemic rats did not change BBB leakage and cerebral plasma perfusion in the contralateral hemisphere. Our results indicate that VEGF can markedly enhance angiogenesis in the ischemic brain and reduce neurological deficits during stroke recovery and that inhibition of VEGF at the acute stage of stroke may reduce the BBB permeability and the risk of hemorrhagic transformation after focal cerebral ischemia.