Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Cell. 2018 Mar 22;173(1):153-165.e22. doi: 10.1016/j.cell.2018.02.004. Epub 2018 Mar 1.
CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.
中枢神经系统损伤常导致轴突断裂。损伤部位局部形成的疤痕组织被认为会阻碍轴突再生，导致永久性功能缺陷。我们报告称，抑制一小部分周细胞的后代生成会导致小鼠脊髓损伤后纤维化和细胞外基质沉积减少。损伤后，减少周细胞来源的疤痕形成会增强中缝核脊髓束和皮质脊髓束轴突的再生，改善感觉运动功能恢复。通过光遗传刺激，我们证明再生的皮质脊髓束轴突整合到损伤部位下方的局部脊髓回路中。再生轴突的数量与感觉运动功能恢复的改善相关。总之，减少周细胞来源的纤维化是一种很有前途的治疗方法，可以促进中枢神经系统损伤后的恢复。
