Alterations in Recovery from Spinal Cord Injury in Rats Treated with Recombinant Human Bone Morphogenetic Protein-2 for Posterolateral Arthrodesis
Alterations in Recovery from Spinal Cord Injury in Rats Treated with Recombinant Human Bone Morphogenetic Protein-2 for Posterolateral Arthrodesis
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DOI：
10.2106/jbjs.j.00904
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发表时间：
2011-08-17
影响因子：
5.3
通讯作者：
Symes, Aviva J.
中科院分区：
文献类型：
--
作者：
Dmitriev, Anton E.;Castner, Suzanne;Symes, Aviva J.
背景资料：使用重组人骨形态发生蛋白-2（rhBMP-2）治疗创伤相关的脊柱不稳定可能是一种可行的选择，但rhBMP-2对受损脊髓的直接影响知之甚少。在目前的研究中，我们研究了急性和长期的影响，使用rhBMP-2在后外侧脊柱的水平脊髓injury in rats.Methods：52只大鼠进行了T10背侧半切，并被分配到两组之一：车辆对照组（24只大鼠）或rhBMP-2组（24只大鼠）。在每组中，根据随访期将动物进一步细分：损伤后1周和6周。对于急性期，另外一组4只大鼠接受重组人血白蛋白，以解释跨种属炎症反应。术后，每周使用旷场量表和数字足迹分析评估运动功能。动物被杀死后，他们被灌注和脊髓分析炎症标志物，胶质细胞增生，细胞外基质蛋白与使用免疫组化。结果：在一个星期，有一个显着增加反应性星形胶质细胞，巨噬细胞-小胶质细胞，成纤维细胞免疫反应周围的rhBMP-2治疗的大鼠相对于对照组的病变。此外，硫酸软骨素蛋白聚糖染色增加。相似的组间形态学差异持续到第6周。在功能上，在急性期，rhBMP-2处理的动物表现出相对于对照组更多的开放视野和精细运动控制缺陷。六周后，两组有相同的功能评分，但与rhBMP-2治疗保留显着更大的爪子角度的变化比control animals.Conclusions：我们的研究结果表明，在大鼠模型中，rhBMP-2使用在附近的穿透性脊髓损伤触发有害的变化，脊髓病变的形态和改变功能恢复。
Background: Treatment of trauma-related spinal instability with use of recombinant human bone morphogenetic protein-2 (rhBMP-2) may appear as a viable option, but little is known of the direct effects of rhBMP-2 on the injured spinal cord. In the current study, we investigated the acute and long-term effects of using rhBMP-2 in the posterolateral spine at the level of a spinal cord injury in rats.Methods: Fifty-two rats underwent a T10 dorsal hemisection and were assigned to one of two groups: the vehicle control group (twenty-four rats) or the rhBMP-2 group (twenty-four rats). Within each group, animals were further subdivided according to the follow-up period: one week and six weeks after the lesion. For the acute phase, an additional group of four rats received recombinant human albumin, to account for the cross-species inflammatory response. Postoperatively, locomotor function was assessed on a weekly basis with use of an open field scale and digital footprint analysis. After the animals were killed, they were perfused and the spinal cords analyzed for inflammatory markers, gliosis, and extracellular matrix proteins with use of immunohistochemistry.Results: At one week, there was a significant increase in reactive astrocyte, macrophage-microglia, and fibroblast immunoreactivity around the lesion in the rhBMP-2-treated rats relative to controls. Additionally, there was increased staining for chondroitin sulfate proteoglycans. Similar intergroup morphologic differences persisted at six weeks. Functionally, in the acute phase, rhBMP-2-treated animals demonstrated more open field and fine motor control deficits relative to the controls. By six weeks, both groups had equivalent functional scores, but those treated with rhBMP-2 retained significantly greater paw angle changes than the control animals.Conclusions: Our findings indicate that in a rat model, rhBMP-2 use in the vicinity of a penetrating spinal cord injury triggers detrimental changes in the morphology of the spinal cord lesion and alters functional recovery.