Anatomical and behavioral characterization of three hemiplegic animal models.

IF 2.3 4区 医学 Q3 NEUROSCIENCES
Mei Liu, Lingling Xu, Gefei Cheng, Yang Yang, Likun Yang, Yuhai Wang
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引用次数: 0

Abstract

Background: 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.

Objective: 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.

Method: 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.

Results: 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.

Conclusion: 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.

Clinical trial number: Not applicable.

三种偏瘫动物模型的解剖学和行为学特征。
背景:偏瘫的特征是身体一侧的肌肉无力,通常由大脑、脊髓或相关神经的损伤引起。这种情况通常是由于中风、创伤性脑损伤(TBI)或脊髓损伤(SCI)引起的,这些损伤会损害皮质脊髓神经元(csn)和皮质脊髓束(CST)。然而,仍然明显缺乏全面的研究,系统地表征这些偏瘫动物模型的解剖和行为方面。目的:本研究旨在验证和比较现有的TBI、卒中和SCI模型,以确定最适合未来研究的临床前偏瘫模型。方法:采用基于病毒的逆行追踪方法,我们首次绘制了负责后肢运动的中枢神经网络的皮质分布。然后采用顺行和逆行病毒追踪技术标记和评估三种模型(光血栓性卒中、Feeney's体重下降性TBI和T10半断面SCI)对csn和CST的损害。我们还进行了行为测试以评估自发运动功能的恢复,包括大运动功能的开阔场地和旋转杆测试,以及评估熟练运动功能的横梁行走和不规则梯子行走任务。结果:我们发现控制后肢运动的中枢神经网络集中在初级体感皮层(S1HL)的后肢区域。在TBI和卒中模型中,S1HL的同侧csn完全破坏,控制后肢运动的CST纤维丢失。在脊髓损伤模型中,T10以下的同侧CST纤维也丢失。损伤后8周,三组偏瘫小鼠的运动功能均有所改善,大运动功能恢复到正常水平;然而,熟练运动功能的恢复只是适度的。值得注意的是,在偏瘫模型中,精细运动技能的改善程度各不相同,遭受脑损伤(中风和TBI)的小鼠在精细运动技能方面的恢复明显高于脊髓损伤小鼠。结论:我们通过损伤cns或CST控制后肢运动来证实和验证先前的偏瘫模型。损伤后,所有组的大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,脑损伤模型与脊髓损伤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宝贵工具。临床试验号:不适用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Neuroscience
BMC Neuroscience 医学-神经科学
CiteScore
3.90
自引率
0.00%
发文量
64
审稿时长
16 months
期刊介绍: BMC Neuroscience is an open access, peer-reviewed journal that considers articles on all aspects of neuroscience, welcoming studies that provide insight into the molecular, cellular, developmental, genetic and genomic, systems, network, cognitive and behavioral aspects of nervous system function in both health and disease. Both experimental and theoretical studies are within scope, as are studies that describe methodological approaches to monitoring or manipulating nervous system function.
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