中国神经再生研究(英文版) ›› 2021, Vol. 21 ›› Issue (5): 2011-2020.doi: 10.4103/NRR.NRR-D-24-01060

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

脊髓损伤后兴奋性和抑制性网状脊髓纤维可塑性差异:对功能恢复的意义

  

  • 出版日期:2026-05-15 发布日期:2025-08-23

Differential plasticity of excitatory and inhibitory reticulospinal fibers after spinal cord injury: Implication for recovery

Rozaria Jeleva1, 2, Carmen Denecke Muhr1, 2, 3, Alina P. Liebisch1, 2, Florence M. Bareyre1, 2, 4, *   

  1. 1 Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, Munich, Germany;  2 Biomedical Center Munich (BMC), Medical Faculty, LMU Munich, Planegg-Martinsried, Germany;  3 Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universitaet Munich, Planegg-Martinsried, Germany;  4 Munich Cluster of Systems Neurology (SyNergy), Munich, Germany
  • Online:2026-05-15 Published:2025-08-23
  • Contact: Florence M. Bareyre, PhD, florence.bareyre@med.uni-muenchen.de.
  • Supported by:
    This study was supported by the Deutsche Forschungsgemeinschaft (DFG), TRR274 (Project ID 408885537; SyNergy; EXC 2145 / ID 390857198; to FMB).

摘要:

损伤后轴突连接的重塑是推动功能恢复的一个重要特征。网状脊髓束(ReST)是一种下降运动束,它同时包含兴奋纤维和抑制纤维。虽然脊髓损伤后网状脊髓束特别容易发生轴突生长和可塑性,但兴奋性纤维和抑制性纤维在可塑性方面的不同能力仍不清楚。由于适应性轴突可塑性涉及兴奋性和抑制性输入之间复杂的相互作用,实验探讨了谷氨酸能神经纤维(vGlut2)和GABA能神经纤维(vGat)的可塑性潜能,这两种纤维起源于巨细胞核(Gi)和外侧旁巨细胞核(LPGi),这两个核对运动功能非常重要。实验采用病毒追踪、化学沉默和基于人工智能的运动学分析相结合的方法,研究了损伤后前三周内的可塑性及其对功能恢复的影响,这一时期容易发生神经元重塑。实验结果显示,在这一时期,颈脊髓损伤后,巨细胞核和外侧旁巨细胞核内的谷氨酸能神经纤维会明显重新接线,而GABA能神经纤维则对损伤反应迟钝。实验还发现,兴奋性轴索纤维在脊髓损伤后重联,其急性沉默会导致功能恢复恶化。通过运动学分析,还确定了在功能恢复期间与巨细胞核或外侧旁巨细胞核相关的运动特征。总之,此研究加深了对脊髓损伤后功能恢复过程中巨细胞核和外侧旁巨细胞核作用的理解。

https://orcid.org/0000-0002-0917-1725 (Florence M. Bareyre)

关键词: 谷氨酸能神经纤维, GABA能神经纤维, 网状脊髓束, 可塑性, 脊髓损伤, 功能恢复, 步态特征

Abstract: The remodeling of axonal connections following injury is an important feature driving functional recovery. The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers. While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord, the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear. As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input, we investigated in this study the plastic potential of glutamatergic (vGlut2) and GABAergic (vGat) fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus, two nuclei important for locomotor function. Using a combination of viral tracing, chemogenetic silencing, and AI-based kinematic analysis, we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury, a period prone to neuronal remodeling. We demonstrate that, in this time frame, while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury, vGat-positive fibers are rather unresponsive to injury. We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery. Using kinematic analysis, we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery. Overall, our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.

Key words: GABAergic (vGat) fibers, gait features, glutamatergic (vGlut2) fibers, plasticity, recovery of function, reticulospinal tract, spinal cord injury