Takatani Hirohide, Fujita Naoki, Imai Fumiyasu, Yoshida Yutaka
Burke Neurological Institute, White Plains, New York, United States.
Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States.
bioRxiv. 2024 Jun 27:2024.06.22.600167. doi: 10.1101/2024.06.22.600167.
Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. Here, we propose the combinatorial approach of deleting extrinsic and intrinsic factors paired with neural stimulation, will enhance adaptive axonal growth and motor recovery after SCI. We previously showed the deletion of and in corticospinal neurons inhibits axon dieback and promotes axon sprouting after lumbar SCI. Here, we examined the effects of deletion coupled with neural stimulation after cervical SCI. This combinatorial approach promoted more boutons on injured corticospinal neurons in the spinal cord compared to sole ; deletion. Although ; deletion does not promote motor recovery in the forelimb after SCI, stimulating corticospinal neurons in those mice results in partial motor recovery. These results demonstrate that a combinatorial approach that pairs genetic modifications with neuronal stimulation can promote axon sprouting and motor recovery following SCI.
人们已经尝试了多种促进脊髓损伤（SCI）后轴突再生和运动恢复的单一策略，但成效有限。在此，我们提出一种组合方法，即去除外在和内在因素并结合神经刺激，这将增强SCI后适应性轴突生长和运动恢复。我们之前表明，在皮质脊髓神经元中去除[具体因子1]和[具体因子2]可抑制腰段SCI后轴突回缩并促进轴突发芽。在此，我们研究了颈段SCI后去除[具体因子]并结合神经刺激的效果。与单纯去除[具体因子]相比，这种组合方法在脊髓中促进了损伤皮质脊髓神经元上更多的轴突终扣。虽然在SCI后去除[具体因子]并不能促进前肢的运动恢复，但刺激这些小鼠的皮质脊髓神经元会导致部分运动恢复。这些结果表明，将基因修饰与神经元刺激相结合的组合方法可促进SCI后的轴突发芽和运动恢复。
