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血管内皮生长因子治疗实验性创伤性脊髓损伤的效果:体内纵向评估。

Effect of vascular endothelial growth factor treatment in experimental traumatic spinal cord injury: in vivo longitudinal assessment.

机构信息

Department of Diagnostic and Interventional Imaging, University of Texas Medical School at Houston, Houston, Texas 77030, USA.

出版信息

J Neurotrauma. 2011 Apr;28(4):565-78. doi: 10.1089/neu.2010.1533. Epub 2011 Mar 24.

Abstract

Vascular endothelial growth factor (VEGF) is thought to provide neuroprotection to the traumatically injured spinal cord. We examined whether supplementing the injured environment with VEGF(165) via direct intraspinal injection into the lesion epicenter during the acute phase of spinal cord injury (SCI) results in improved outcome. The effect of treatment was investigated using longitudinal multi-modal magnetic resonance imaging (MRI), neurobehavioral assays, and end-point immunohistochemistry. We observed on MRI that rats treated with VEGF(165) after SCI had increased tissue sparing compared to vehicle-treated animals at the earlier time points. However, these favorable effects were not maintained into the chronic phase. Histology revealed that VEGF(165) treatment resulted in increased oligodendrogenesis and/or white matter sparing, and therefore may eventually lead to improved functional outcome. The increase in spared tissue as demonstrated by MRI, coupled with the possible remyelination and increased neurosensory sensitivity, suggests that VEGF(165) treatment may play a role in promoting plasticity in the sensory pathways following SCI. However, VEGF-treated animals also demonstrated an increased incidence of persistent allodynia, as indicated on the von Frey filament test.

摘要

血管内皮生长因子(VEGF)被认为可以对创伤性脊髓损伤提供神经保护作用。我们通过在脊髓损伤(SCI)的急性期向损伤中心直接进行椎管内注射,研究了向损伤环境中补充 VEGF(165)是否会改善结果。通过纵向多模态磁共振成像(MRI)、神经行为学检测和终点免疫组织化学,我们对治疗效果进行了研究。我们在 MRI 上观察到,与接受载体治疗的动物相比,SCI 后接受 VEGF(165)治疗的大鼠在早期时间点有更多的组织保留。然而,这些有利的效果并没有维持到慢性期。组织学显示,VEGF(165)治疗导致少突胶质细胞增生和/或白质保留增加,因此最终可能导致功能结果改善。MRI 显示的组织保留增加,再加上可能的髓鞘再生和增加的神经感觉敏感性,表明 VEGF(165)治疗可能在 SCI 后促进感觉通路的可塑性中发挥作用。然而,接受 VEGF 治疗的动物也表现出持续性触诱发痛的发生率增加,这在 von Frey 纤维试验中有所表明。

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