Chehrehasa Fatemeh, Cobcroft Mitchell, Young Yun Wai, Mackay-Sim Alan, Goss Ben
1 Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane QLD, Australia .
J Neurotrauma. 2014 Nov 1;31(21):1807-13. doi: 10.1089/neu.2013.3294. Epub 2014 Sep 4.
Inflammation of the spinal cord after traumatic spinal cord injury (SCI) leads to destruction of healthy tissue. This "secondary degeneration" is more damaging than the initial physical damage and is the major contributor to permanent loss of functions. In our previous study, we showed that combined delivery of two growth factors, vascular endothelial growth factor and platelet-derived growth factor, significantly reduced secondary degeneration after hemisection injury of the spinal cord in the rat. Growth factor treatment reduced the size of the lesion cavity at 30 days, compared to control animals, and further reduced the cavity at 90 days in treated animals, whereas in control animals the lesion cavity continued to increase in size. Growth factor treatment also reduced astrogliosis and reduced macroglia/macrophage activation around the injury site. Treatment with individual growth factors alone had similar effects to control treatments. The present study investigated whether growth factor treatment would improve locomotor behavior after spinal contusion injury, a more relevant pre-clinical model of SCI. The growth factors were delivered for the first 7 days to the injury site by osmotic minipump. Locomotor behavior was monitored at 1-28 days after injury using the Basso, Beattie and Bresnahan (BBB) score and at 30 days using automated gait analysis. Treated animals had BBB scores of 18; control animals scored 10. Treated animals had significantly reduced lesion cavities and reduced macroglia/macrophage activation around the injury site. We conclude that growth factor treatment preserved spinal cord tissues after contusion injury, thereby allowing functional recovery. This treatment has the potential to significantly reduce the severity of human spinal cord injuries.
创伤性脊髓损伤(SCI)后脊髓的炎症会导致健康组织的破坏。这种“继发性变性”比最初的物理损伤更具破坏性,是导致功能永久性丧失的主要因素。在我们之前的研究中,我们表明联合递送两种生长因子,即血管内皮生长因子和血小板衍生生长因子,可显著减少大鼠脊髓半切损伤后的继发性变性。与对照动物相比,生长因子治疗在30天时减小了损伤腔的大小,并且在治疗动物中90天时进一步减小了损伤腔,而在对照动物中损伤腔的大小持续增加。生长因子治疗还减少了星形胶质细胞增生,并减少了损伤部位周围的大胶质细胞/巨噬细胞活化。单独使用单个生长因子进行治疗与对照治疗具有相似的效果。本研究调查了生长因子治疗是否会改善脊髓挫伤损伤后的运动行为,脊髓挫伤损伤是一种更相关的SCI临床前模型。通过渗透微型泵在损伤后的前7天将生长因子递送至损伤部位。在损伤后1至28天使用Basso、Beattie和Bresnahan(BBB)评分监测运动行为,并在30天时使用自动步态分析。治疗动物的BBB评分为18;对照动物评分为10。治疗动物的损伤腔明显减小,损伤部位周围的大胶质细胞/巨噬细胞活化减少。我们得出结论,生长因子治疗在挫伤损伤后保留了脊髓组织,从而实现了功能恢复。这种治疗方法有可能显著降低人类脊髓损伤的严重程度。