Liu Mei, Xu Lingling, Cheng Gefei, Yang Yang, Yang Likun, Wang Yuhai
Department of Neurosurgery, Wuxi Clinical College of Anhui Medical University (The 904 th Hospital of PLA), Wuxi, 214044, Jiangsu, China.
BMC Neurosci. 2025 Jul 21;26(1):44. doi: 10.1186/s12868-025-00961-9.
Hemiplegia is characterized by muscle weakness on one side of the body, often resulting from damage to the brain, spinal cord, or associated nerves. This condition commonly occurs due to strokes, traumatic brain injuries (TBI), or spinal cord injuries (SCI), which can damage corticospinal neurons (CSNs) and the corticospinal tract (CST). However, there is still a notable lack of comprehensive studies that systematically characterize the anatomical and behavioral aspects of these hemiplegic animal models.
This study aimed to validate and compare existing models of TBI, stroke, and SCI in order to identify the most suitable preclinical hemiplegia models for future research.
Using viral-based retrograde tracing, we first mapped the cortical distribution of CSNs responsible for hindlimb movement. Anterograde and retrograde viral tracing techniques were then employed to label and evaluate the damage to CSNs and the CST in three models: photothrombotic stroke, Feeney's weight-drop TBI, and T10 hemi-section SCI. We also conducted behavioral tests to assess spontaneous motor function recovery, including open field and rotarod tests for gross motor function, as well as beam walking and irregular ladder walking tasks for assessing skilled motor function.
Our findings revealed that the CSNs controlling hindlimb movement are concentrated in the hindlimb region of the primary somatosensory cortex (S1HL). In the TBI and stroke models, there was complete destruction of ipsilateral CSNs in the S1HL and loss of CST fibers governing hindlimb movement. In the SCI model, ipsilateral CST fibers below T10 were also lost. After 8 weeks post-injury, all three groups of hemiplegic mice showed improvements in motor function, with gross motor function returning to normal levels; however, the recovery of skilled motor function was only modest. Notably, the degree of improvement in fine motor skills varied among the hemiplegia models, with mice subjected to brain injury (stroke and TBI) demonstrating significantly greater recovery in fine motor skills compared to those with SCI.
We confirmed and validated previous hemiplegia models by damaging CSNs or CST controlling hindlimb movement. Post-injury, gross motor function gradually returned to normal levels across all groups, whereas recovery of skilled motor function was limited. Furthermore, there were significant differences in the recovery of skilled motor function between brain injury models and the SCI model. These hemiplegic mouse models are valuable tools for studying post-injury skilled motor functions.
Not applicable.
偏瘫的特征是身体一侧肌肉无力，通常由大脑、脊髓或相关神经受损引起。这种情况常见于中风、创伤性脑损伤（TBI）或脊髓损伤（SCI），这些损伤可损害皮质脊髓神经元（CSN）和皮质脊髓束（CST）。然而，仍然明显缺乏系统描述这些偏瘫动物模型解剖学和行为学方面的综合研究。
本研究旨在验证和比较现有的TBI、中风和SCI模型，以确定最适合未来研究的临床前偏瘫模型。
我们首先使用基于病毒的逆行追踪技术绘制负责后肢运动的CSN的皮质分布。然后采用顺行和逆行病毒追踪技术标记和评估三种模型中CSN和CST的损伤情况：光血栓性中风、Feeney的重物坠落性TBI和T10半横断SCI。我们还进行了行为测试以评估自发运动功能恢复情况，包括用于评估总体运动功能的旷场试验和转棒试验，以及用于评估熟练运动功能的光束行走和不规则阶梯行走任务。
我们的研究结果表明，控制后肢运动的CSN集中在初级体感皮层（S1HL）的后肢区域。在TBI和中风模型中，S1HL同侧的CSN完全被破坏，支配后肢运动的CST纤维丧失。在SCI模型中，T10以下的同侧CST纤维也丧失。损伤后8周，所有三组偏瘫小鼠的运动功能均有改善，总体运动功能恢复到正常水平；然而，熟练运动功能的恢复程度有限。值得注意的是，精细运动技能的改善程度在不同的偏瘫模型中有所不同，与SCI小鼠相比，脑损伤（中风和TBI）小鼠的精细运动技能恢复明显更好。
我们通过损伤控制后肢运动的CSN或CST，证实并验证了先前的偏瘫模型。损伤后，所有组的总体运动功能逐渐恢复到正常水平，而熟练运动功能的恢复有限。此外，脑损伤模型和SCI模型在熟练运动功能恢复方面存在显著差异。这些偏瘫小鼠模型是研究损伤后熟练运动功能的有价值工具。
不适用。
