Hanasaki Takuto, Hanaki Keita, Sako Yukito, Uchiyama Yasushi, Lee-Hotta Sachiko
Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
Division of Creative Physical Therapy, Department of Integrated Health Sciences, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
Sci Rep. 2025 Jul 3;15(1):23764. doi: 10.1038/s41598-025-09397-x.
Spasticity is defined as the velocity-dependent hyperexcitability of the stretch reflex that develops after a central nervous system injury. Spasticity is caused by plastic neuronal changes following injury. Current treatments that block spastic muscle contractions do not promote recovery from motor dysfunction. We aimed to confirm that Ia fibre activity suppression, comprising the stretch reflex, reduces spasticity-related hyperreflexia and improves pathological neuronal plastic changes and motor dysfunction. In this study, we created a hemi-transected spinal cord injury mouse model and continued Ia fibre suppression for 2 weeks. The effects of Ia fibre suppression were evaluated electrophysiologically and histologically. In electrophysiology, spasticity-related rate-dependent depression of Hoffman's reflex improved from 0.6 to 0.2 in terms of the rate of amplitude change with reference to 0.1 Hz electrical stimulation. Histologically, the number of synapse buttons of Ia fibres per an α motor neuron reduced from 4.2 to 2.6. However, the α motor neuron activity was still higher than that in the sham mice, possibly due to other residual pathological mechanisms of spasticity. Additionally, motor dysfunction was observed in grid walk and single-reach tasks in vehicle- and drug-administered groups. This study confirmed that continuous Ia fibre suppression partly improved the maladaptive synaptic connections in the spinal cord and relieved spasticity-related hyperreflexia.
痉挛被定义为中枢神经系统损伤后出现的牵张反射速度依赖性过度兴奋。痉挛是由损伤后神经元可塑性变化引起的。目前阻断痉挛性肌肉收缩的治疗方法并不能促进运动功能障碍的恢复。我们旨在证实，抑制构成牵张反射的Ia纤维活动，可减少与痉挛相关的反射亢进，并改善病理性神经元可塑性变化和运动功能障碍。在本研究中，我们创建了半横断脊髓损伤小鼠模型，并持续抑制Ia纤维2周。通过电生理学和组织学方法评估Ia纤维抑制的效果。在电生理学方面，相对于0.1Hz电刺激，与痉挛相关的霍夫曼反射的频率依赖性抑制在幅度变化率方面从0.6提高到了0.2。在组织学上，每个α运动神经元的Ia纤维突触纽扣数量从4.2减少到2.6。然而，α运动神经元活动仍高于假手术小鼠，这可能是由于痉挛的其他残留病理机制所致。此外，在给予载体和药物的组中，在网格行走和单次伸手任务中均观察到运动功能障碍。本研究证实，持续抑制Ia纤维可部分改善脊髓中适应性不良的突触连接，并缓解与痉挛相关的反射亢进。
