Surey S, Berry M, Logan A, Bicknell R, Ahmed Z
Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
CRUK Molecular Angiogenesis Group, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK.
Neuroscience. 2014 Sep 5;275:62-80. doi: 10.1016/j.neuroscience.2014.06.003. Epub 2014 Jun 11.
The vascular disruption, blood vessel loss and cavitation that occur at spinal cord injury (SCI) epicenters in mice and rats are different, but few studies have compared the acute SCI response in the two species. This is of interest since key elements of the rat SCI response are shared with humans. In this study, we investigated acute SCI responses and characterized changes in pro- and anti-angiogenic factors and matrix deposition in both species. Cavitation was absent in mouse but the area of the lesion site was 21- and 27-fold larger at 8 and 15 days post-lesion (dpl), respectively, in the rat compared to intact control. The absence of wound cavitation in the mouse was correlated with increased levels of immunoreactive pro-angiogenic, pro-matrix and pro-wound-healing factors, e.g. laminin, matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor-A (VEGF-A) within the wound, which were 6.0-, 2.9-, and 2.8-fold, respectively, higher in the mouse compared to rats at 8 dpl. Increased axonal sparing was observed after dorsal column (DC) injury, detected by higher levels of neurofilament 200 (NF200) immunoreactivity in the dorsal column of mice compared to rats at both T7 and T9 spinal segments. Despite similar post SCI deficits in plantar heat tests at 2h after injury (1.4- and 1.6-fold lower than control mice and rats, respectively), by 7 days the magnitude of these responses were comparable to sham-treated controls in both species, while no post-SCI changes in Von Frey hair filament test response were observed in either species. We conclude that the more robust angiogenesis/wound-healing response in the mouse attenuates post-injury wound cavitation. Although the spinal cord functions that were monitored post-injury were similarly affected in both species, we suggest that the quality of the angiogenesis/wound-healing response together with the diminished lesion size seen after mouse SCI may protect against secondary axon damage and create an environment more conducive to axon sprouting/regeneration. These results suggest the potential therapeutic utility of manipulating the angiogenic response after human SCI.
小鼠和大鼠脊髓损伤（SCI）中心部位发生的血管破坏、血管损失和空洞形成有所不同，但很少有研究比较这两个物种的急性SCI反应。鉴于大鼠SCI反应的关键要素与人类相同，这一点很值得关注。在本研究中，我们调查了两个物种的急性SCI反应，并对促血管生成和抗血管生成因子以及基质沉积的变化进行了特征描述。小鼠未出现空洞形成，但与完整对照组相比，大鼠在损伤后8天（dpl）和15天的损伤部位面积分别大21倍和27倍。小鼠伤口无空洞形成与伤口内免疫反应性促血管生成、促基质和促伤口愈合因子水平升高相关，例如层粘连蛋白、基质金属蛋白酶-1（MMP-1）和血管内皮生长因子-A（VEGF-A），在损伤后8天，小鼠体内这些因子的水平分别比大鼠高6.0倍、2.9倍和2.8倍。在背柱（DC）损伤后观察到轴突保留增加，通过在T7和T9脊髓节段检测发现，与大鼠相比，小鼠背柱中神经丝200（NF200）免疫反应性水平更高。尽管在损伤后2小时的足底热测试中，两个物种的SCI后缺陷相似（分别比对照小鼠和大鼠低1.4倍和1.6倍），但到7天时，两个物种这些反应的幅度与假手术对照组相当，而在两个物种中均未观察到SCI后Von Frey毛发丝测试反应的变化。我们得出结论，小鼠中更强有力的血管生成/伤口愈合反应可减轻损伤后伤口空洞形成。尽管在损伤后监测的脊髓功能在两个物种中受到的影响相似，但我们认为血管生成/伤口愈合反应的质量以及小鼠SCI后较小的损伤尺寸可能会防止继发性轴突损伤，并创造一个更有利于轴突发芽/再生的环境。这些结果表明，在人类SCI后操纵血管生成反应具有潜在的治疗效用。
