Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
J Neurotrauma. 2012 Mar 20;29(5):957-70. doi: 10.1089/neu.2010.1423. Epub 2011 Aug 9.
Trauma to the spinal cord creates an initial physical injury damaging neurons, glia, and blood vessels, which then induces a prolonged inflammatory response, leading to secondary degeneration of spinal cord tissue, and further loss of neurons and glia surrounding the initial site of injury. Angiogenesis is a critical step in tissue repair, but in the injured spinal cord angiogenesis fails; blood vessels formed initially later regress. Stabilizing the angiogenic response is therefore a potential target to improve recovery after spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) can initiate angiogenesis, but cannot sustain blood vessel maturation. Platelet-derived growth factor (PDGF) can promote blood vessel stability and maturation. We therefore investigated a combined application of VEGF and PDGF as treatment for traumatic spinal cord injury, with the aim to reduce secondary degeneration by promotion of angiogenesis. Immediately after hemisection of the spinal cord in the rat we delivered VEGF and PDGF and to the injury site. One and 3 months later the size of the lesion was significantly smaller in the treated group compared to controls, and there was significantly reduced gliosis surrounding the lesion. There was no significant effect of the treatment on blood vessel density, although there was a significant reduction in the numbers of macrophages/microglia surrounding the lesion, and a shift in the distribution of morphological and immunological phenotypes of these inflammatory cells. VEGF and PDGF delivered singly exacerbated secondary degeneration, increasing the size of the lesion cavity. These results demonstrate a novel therapeutic intervention for SCI, and reveal an unanticipated synergy for these growth factors whereby they modulated inflammatory processes and created a microenvironment conducive to axon preservation/sprouting.
脊髓创伤会造成初始的物理性神经元、神经胶质细胞和血管损伤，继而引发长期的炎症反应，导致脊髓组织的继发性变性，以及初始损伤部位周围神经元和神经胶质细胞的进一步丧失。血管生成是组织修复的关键步骤，但在受伤的脊髓中，血管生成失败；最初形成的血管随后退化。因此，稳定血管生成反应是改善脊髓损伤（SCI）后恢复的一个潜在目标。血管内皮生长因子（VEGF）可以引发血管生成，但不能维持血管成熟。血小板衍生生长因子（PDGF）可以促进血管稳定性和成熟。因此，我们研究了 VEGF 和 PDGF 的联合应用作为创伤性脊髓损伤的治疗方法，旨在通过促进血管生成来减少继发性变性。在大鼠脊髓半切后，我们立即将 VEGF 和 PDGF 递送到损伤部位。在治疗 1 个月和 3 个月后，与对照组相比，治疗组的损伤大小明显较小，并且损伤周围的神经胶质增生明显减少。该治疗对血管密度没有显著影响，尽管损伤周围的巨噬细胞/小胶质细胞数量显著减少，并且这些炎症细胞的形态和免疫表型分布发生了变化。VEGF 和 PDGF 单独给药加剧了继发性变性，增加了损伤腔的大小。这些结果证明了 SCI 的一种新的治疗干预措施，并揭示了这些生长因子的一种意外协同作用，即它们调节了炎症过程，并创造了有利于轴突保存/发芽的微环境。
