Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury
Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury
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DOI：
10.1016/s0306-4522(03)00399-3
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发表时间：
2003-09
期刊：
影响因子：
3.3
通讯作者：
J. Widenfalk;A. Lipson;Marie Jubran;C. Hofstetter;T. Ebendal;Yihai Cao;L. Olson
中科院分区：
文献类型：
--
作者：
J. Widenfalk;A. Lipson;Marie Jubran;C. Hofstetter;T. Ebendal;Yihai Cao;L. Olson
脊髓损伤导致急性局部缺血，这可能有助于继发性变性。缺氧通过一系列事件刺激血管生成，涉及血管生成刺激物质，如血管内皮生长因子（VEGF）。为了测试血管生成对于脊髓损伤中的功能结果和伤口愈合的重要性，在使用NYU撞击器和25 mm重物下落产生的挫伤损伤后立即局部递送VEGF 165（促血管生成）、林格氏液（对照）或血管抑素（抗血管生成）。与对照动物相比，VEGF治疗的大鼠在损伤后6周表现出显著改善的行为，而血管抑素治疗导致行为结果没有统计学显著变化。此外，与对照组相比，VEGF治疗的动物在病变中心的备用组织数量增加，部分伤口区域的血管密度更高。这些影响不太可能是由于溴脱氧尿苷标记确定的细胞增殖增加。此外，VEGF治疗导致细胞凋亡水平降低，如TUNEL检测所示。原位杂交表明，在脊髓的几个重要的细胞室VEGF受体Flt-1，胎肝激酶-1，neuropilin-1和-2的mRNA的存在。不同的实验表明，通过急性VEGF递送观察到的有益效果归因于血管的保护/修复、细胞凋亡的减少，并且还可能归因于对神经胶质细胞或某些神经元群体的其他额外作用。
Spinal cord injury leads to acute local ischemia, which may contribute to secondary degeneration. Hypoxia stimulates angiogenesis through a cascade of events, involving angiogenesis stimulatory substances, such as vascular endothelial growth factor (VEGF). To test the importance of angiogenesis for functional outcome and wound healing in spinal cord injury VEGF165 (proangiogenic), Ringer's (control) or angiostatin (antiangiogenic) were delivered locally immediately after a contusion injury produced using the NYU impactor and a 25 mm weight-drop. Rats treated with VEGF showed significantly improved behavior up to 6 weeks after injury compared with control animals, while angiostatin treatment lead to no statistically significant changes in behavior outcome. Furthermore, VEGF-treated animals had an increased amount of spared tissue in the lesion center and a higher blood vessel density in parts of the wound area compared with controls. These effects were unlikely to be due to increased cell proliferation as determined by bromo-deoxy-uridine-labeling. Moreover, VEGF treatment led to decreased levels of apoptosis, as revealed by TUNEL assays. In situ hybridization demonstrated presence of mRNA for VEGF receptors Flt-1, fetal liver kinase-1, neuropilin-1 and -2 in several important cellular compartments of the spinal cord. The different experiments indicate that beneficial effects seen by acute VEGF delivery was attributable to protection/repair of blood vessels, decreased apoptosis and possibly also by other additional effects on glial cells or certain neuron populations.