Photodynamic Therapy Mediated by Upconversion Nanoparticles to Reduce Glial Scar Formation and Promote Hindlimb Functional Recovery After Spinal Cord Injury in Rats.
Photodynamic Therapy Mediated by Upconversion Nanoparticles to Reduce Glial Scar Formation and Promote Hindlimb Functional Recovery After Spinal Cord Injury in Rats.
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DOI：
10.1166/jbn.2016.2300
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发表时间：
2016-11
影响因子：
2.9
通讯作者：
Yang Liu;D. Ban;Chao Ma;Zhi-guo Zhang;Jiayin Zhang;Shijie Gao;S. Feng
中科院分区：
文献类型：
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作者：
Yang Liu;D. Ban;Chao Ma;Zhi-guo Zhang;Jiayin Zhang;Shijie Gao;S. Feng
胶质瘢痕形成是脊髓损伤后的主要后果之一，它阻碍再生轴突通过损伤区并形成有效的突触连接。本研究采用聚乙二醇（PEG）和光敏剂（UCNPs-PEGM 540）上转换纳米粒子介导的光动力学疗法（PDT）治疗脊髓损伤后胶质瘢痕形成。体外实验结果表明，近红外光激发后，上转换纳米粒子可杀死培养的星形胶质细胞。将UCNPs-PEG-M540移植于脊髓损伤中心区边缘区，采用Basso、Beattie、Bresnahan运动功能评定量表评价大鼠后肢功能恢复情况。通过胶质细胞酸性蛋白染色、神经纤维素染色、生物素葡聚糖胺顺行追踪和蛋白质印迹法评价损伤脊髓微环境的改善。实验结果表明，将UCNPs-PEG-M540移植到损伤脊髓内，可使更多的皮质脊髓束再生轴突环绕并穿过损伤腔到达尾髓。总之，我们的研究结果强烈表明，上转换纳米粒子结合光动力疗法可以通过减少胶质瘢痕的形成和促进受损轴突的髓鞘再生来促进大鼠后肢的功能恢复。
Glial scar formation is one of the major consequences of spinal cord injury, which prevents the regenerated axons passing the injured area and forming effective synaptic connection. In this paper, we used photodynamic therapy (PDT), which was mediated by the upconversion nanoparticles coated with polyethylene glycol (PEG) and photosensitizer (UCNPs-PEGM540), to reduce the glial scar formation after spinal cord injury. The in vitro experimental results indicated that cultured astrocytes could be killed by using upconversion nanoparticles after excitation with near infrared light. By transplanting UCNPs-PEG-M540 into the margin area of injured epicenter of spinal cord, the recovery of rat's hindlimb function was evaluated in Basso, Beattie, Bresnahan locomotor rating scale, respectively. The improvement in microenvironment of the injured spinal cord was also evaluated by glial fibrillary acidic protein staining, neurofiliment staining, biotinylated dextran amine anterograde tracing and western blotting. Our results demonstrated that more regenerative axons of corticospinal tract were found to surround and pass through the injured cavity to the caudal cord with transplanting UCNPs-PEG-M540 into the injured spinal cord. In conclusion, our results strongly suggested that upconversion nanoparticles combined with photodynamic therapy can promote functional recovery in rats' hindlimbs by reducing the formation of glial scar and promoting remyelination of injured axons.