The Janus Face of VEGF in Stroke.
The Janus Face of VEGF in Stroke.
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DOI：
10.3390/ijms19051362
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发表时间：
2018-05-04
影响因子：
5.6
通讯作者：
Morland C
中科院分区：
文献类型：
--
作者：
Geiseler SJ;Morland C
血管内皮生长因子 (VEGF) 家族以其对血管形成的调节而闻名。在大脑中，VEGF 是血管生成、神经保护和神经发生的重要调节因子。 VEGF 失调与大量神经退行性疾病和急性神经损伤（包括中风）有关。中风是获得性残疾的主要原因，通常由脑动脉闭塞或出血引起，两者都会导致局灶性缺血。缺血核心的神经元迅速坏死。半暗带中的细胞处于缺血状态，但如果及时恢复足够的灌注，则可能会得到挽救。理论上，VEGF 的神经保护和血管生成作用将使 VEGF 成为中风药物治疗的理想候选者。然而，与人们的预期相反，内源性上调的 VEGF 水平以及外源性 VEGF 的施用对急性中风是有害的。这可能是由于 VEGF 介导的血脑屏障破坏和血管渗漏，导致水肿、颅内压升高以及神经炎症。理解中风中 VEGF 功能的两面性的关键可能在于时间。 VEGF 对血管完整性的有害影响是短暂的，因为 VEGF 预处理和急性期后增加 VEGF 都具有神经保护作用。本综述讨论了 VEGF 在中风预防和治疗中的多方面作用。
The family of vascular endothelial growth factors (VEGFs) are known for their regulation of vascularization. In the brain, VEGFs are important regulators of angiogenesis, neuroprotection and neurogenesis. Dysregulation of VEGFs is involved in a large number of neurodegenerative diseases and acute neurological insults, including stroke. Stroke is the main cause of acquired disabilities, and normally results from an occlusion of a cerebral artery or a hemorrhage, both leading to focal ischemia. Neurons in the ischemic core rapidly undergo necrosis. Cells in the penumbra are exposed to ischemia, but may be rescued if adequate perfusion is restored in time. The neuroprotective and angiogenic effects of VEGFs would theoretically make VEGFs ideal candidates for drug therapy in stroke. However, contradictory to what one might expect, endogenously upregulated levels of VEGF as well as the administration of exogenous VEGF is detrimental in acute stroke. This is probably due to VEGF-mediated blood–brain-barrier breakdown and vascular leakage, leading to edema and increased intracranial pressure as well as neuroinflammation. The key to understanding this Janus face of VEGF function in stroke may lie in the timing; the harmful effect of VEGFs on vessel integrity is transient, as both VEGF preconditioning and increased VEGF after the acute phase has a neuroprotective effect. The present review discusses the multifaceted action of VEGFs in stroke prevention and therapy.
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影响因子：
82.9
作者：
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发表时间：
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影响因子：
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