Development of a mouse model of chronic ventral spinal cord compression: Neurobehavioral, radiological, and pathological changes

IF 3.4 3区医学 Q1 ORTHOPEDICS JOR Spine Pub Date : 2024-07-10 DOI:10.1002/jsp2.1350

Zhongyuan He, Tao Tang, Zhengya Zhu, Fuan Wang, Jianfeng Li, Fu Zhang, Nguyen Tran Canh Tung, Shaoyu Liu, Xizhe Liu, Zhiyu Zhou

{"title":"Development of a mouse model of chronic ventral spinal cord compression: Neurobehavioral, radiological, and pathological changes","authors":"Zhongyuan He, Tao Tang, Zhengya Zhu, Fuan Wang, Jianfeng Li, Fu Zhang, Nguyen Tran Canh Tung, Shaoyu Liu, Xizhe Liu, Zhiyu Zhou","doi":"10.1002/jsp2.1350","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objectives</h3>\n \n <p>The main objective of this study was to establish a mouse model of spinal ligament ossification to simulate the chronic spinal cord compression observed in patients with ossification of the posterior longitudinal ligament (OPLL). The study also aimed to examine the mice's neurobiological, radiological, and pathological changes.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In the previous study, a genetically modified mouse strain was created using Crispr-Cas9 technology, namely, <i>Enpp1</i><sup><i>flox/flox</i></sup>/<i>EIIa-Cre</i> (C57/B6 background), to establish the OPLL model. Wild-type (WT) mice without compression were used as controls. Functional deficits were evaluated through motor score assessment, inclined plate testing, and gait analysis. The extent of compression was determined using CT imaging. Hematoxylin and eosin staining, luxol fast blue staining, TUNEL assay, immunofluorescence staining, qPCR, and Western blotting were performed to evaluate levels of apoptosis, inflammation, vascularization, and demyelination in the study.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The results demonstrated a gradual deterioration of compression in the <i>Enpp1</i><sup><i>flox/flox</i></sup>/<i>EIIa-Cre</i> mice group as they aged. The progression rate was more rapid between 12 and 20 weeks, followed by a gradual stabilization between 20 and 28 weeks. The scores for spinal cord function and strength, assessed using the Basso Mouse Scale and inclined plate test, showed a significant decline. Gait analysis revealed a noticeable reduction in fore and hind stride lengths, stride width, and toe spread. Chronic spinal cord compression resulted in neuronal damage and activated astrocytes and microglia in the gray matter and anterior horn. Progressive posterior cervical compression impeded blood supply, leading to inflammation and Fas-mediated neuronal apoptosis. The activation of Bcl2 and Caspase 3 was associated with the development of progressive neurological deficits (<i>p</i> < 0.05).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The study presents a validated model of chronic spinal cord compression, enabling researchers to explore clinically relevant therapeutic approaches for OPLL.</p>\n </section>\n </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237184/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOR Spine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jsp2.1350","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives

The main objective of this study was to establish a mouse model of spinal ligament ossification to simulate the chronic spinal cord compression observed in patients with ossification of the posterior longitudinal ligament (OPLL). The study also aimed to examine the mice's neurobiological, radiological, and pathological changes.

Methods

In the previous study, a genetically modified mouse strain was created using Crispr-Cas9 technology, namely, Enpp1^flox/flox/EIIa-Cre (C57/B6 background), to establish the OPLL model. Wild-type (WT) mice without compression were used as controls. Functional deficits were evaluated through motor score assessment, inclined plate testing, and gait analysis. The extent of compression was determined using CT imaging. Hematoxylin and eosin staining, luxol fast blue staining, TUNEL assay, immunofluorescence staining, qPCR, and Western blotting were performed to evaluate levels of apoptosis, inflammation, vascularization, and demyelination in the study.

Results

The results demonstrated a gradual deterioration of compression in the Enpp1^flox/flox/EIIa-Cre mice group as they aged. The progression rate was more rapid between 12 and 20 weeks, followed by a gradual stabilization between 20 and 28 weeks. The scores for spinal cord function and strength, assessed using the Basso Mouse Scale and inclined plate test, showed a significant decline. Gait analysis revealed a noticeable reduction in fore and hind stride lengths, stride width, and toe spread. Chronic spinal cord compression resulted in neuronal damage and activated astrocytes and microglia in the gray matter and anterior horn. Progressive posterior cervical compression impeded blood supply, leading to inflammation and Fas-mediated neuronal apoptosis. The activation of Bcl2 and Caspase 3 was associated with the development of progressive neurological deficits (p < 0.05).

Conclusions

The study presents a validated model of chronic spinal cord compression, enabling researchers to explore clinically relevant therapeutic approaches for OPLL.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

慢性腹侧脊髓压迫小鼠模型的开发：神经行为、放射学和病理学变化

研究目的本研究的主要目的是建立脊柱韧带骨化小鼠模型，以模拟后纵韧带骨化（OPLL）患者的慢性脊髓压迫症状。研究还旨在检测小鼠的神经生物学、放射学和病理学变化：在之前的研究中，我们利用 Crispr-Cas9 技术创建了一个转基因小鼠品系，即 Enpp1 flox/flox /EIIa-Cre （C57/B6 背景），以建立 OPLL 模型。无压迫的野生型（WT）小鼠作为对照组。通过运动评分评估、倾斜板测试和步态分析评估功能障碍。通过 CT 成像确定压迫程度。研究中进行了血红素和伊红染色、鲁索快蓝染色、TUNEL检测、免疫荧光染色、qPCR和Western印迹，以评估细胞凋亡、炎症、血管化和脱髓鞘的水平：结果表明，随着年龄的增长，Enpp1 flox/flox /EIIa-Cre 小鼠组的压迫症状逐渐恶化。在12周至20周期间，恶化速度更快，随后在20周至28周期间逐渐趋于稳定。使用巴索小鼠量表和斜板试验评估的脊髓功能和力量评分显示出明显的下降。步态分析显示，前后步长、步幅和脚趾张开度明显下降。慢性脊髓压迫导致神经元损伤，激活了灰质和前角的星形胶质细胞和小胶质细胞。颈椎后部的逐渐压迫阻碍了血液供应，导致炎症和 Fas 介导的神经细胞凋亡。Bcl2 和 Caspase 3 的激活与进行性神经功能缺损的发展有关（p 结论）：该研究提出了一种经过验证的慢性脊髓压迫模型，使研究人员能够探索与临床相关的 OPLL 治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊