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挫伤、脱位和牵张性脊髓损伤中轴突和髓鞘变化的自动定量分析:对靶向髓鞘再生和轴突再生的见解

Automated quantification of axonal and myelin changes in contusion, dislocation, and distraction spinal cord injuries: Insights into targeted remyelination and axonal regeneration.

作者信息

Li Xuan, He Yuan, Chen Fangyao, Tong Xin, Fan Yunlong, Langzhou Yuzhe, Liu Jie, Chen Kinon

机构信息

Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University - Yifu Science Hall, 37 Xueyuan Road, Haidian, Beijing 100191, China.

Institute of Trauma & Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, China.

出版信息

Brain Res Bull. 2025 Feb;221:111193. doi: 10.1016/j.brainresbull.2025.111193. Epub 2025 Jan 6.

Abstract

Quantifying axons and myelin is essential for understanding spinal cord injury (SCI) mechanisms and developing targeted therapies. This study proposes and validates an automated method to measure axons and myelin, applied to compare contusion, dislocation, and distraction SCIs in a rat model. Spinal cords were processed and stained for neurofilament, tubulin, and myelin basic protein, with histology images segmented into dorsal, lateral, and ventral white matter regions. Custom MATLAB scripts identified axons and myelin through brightness-based object detection and shape analysis, followed by an iterative dilation process to differentiate myelinated from unmyelinated axons. Validation showed a high correlation with manual counts of total and myelinated axons, with no significant differences between methods. Application of this method revealed distinct injury-specific changes: dislocation caused the greatest axonal loss, while distraction led to the lowest myelin-to-axon-area ratio, indicating preserved axons but severe demyelination. All injuries resulted in increased axon diameter and a decreased myelin-sheath-thickness-to-axon-diameter ratio, suggesting disrupted myelination. These results indicate that remyelination therapies may be most effective for distraction injuries, where preserved axons make remyelination crucial, while axonal regeneration therapies are likely better suited for dislocation injuries with extensive axonal loss. Contusion injuries, involving both axonal and myelin damage, may benefit from a combination of neuroprotective and remyelination strategies. These findings highlight the importance of tailoring treatments to the distinct pathophysiological features of each SCI type to optimize recovery outcomes.

摘要

量化轴突和髓鞘对于理解脊髓损伤(SCI)机制以及开发靶向治疗方法至关重要。本研究提出并验证了一种测量轴突和髓鞘的自动化方法,并将其应用于比较大鼠模型中的挫伤、脱位和牵张性脊髓损伤。对脊髓进行处理,并用神经丝、微管蛋白和髓鞘碱性蛋白进行染色,将组织学图像分割为背侧、外侧和腹侧白质区域。定制的MATLAB脚本通过基于亮度的目标检测和形状分析来识别轴突和髓鞘,随后通过迭代扩张过程区分有髓鞘和无髓鞘轴突。验证结果表明,该方法与手动计数的总轴突和有髓鞘轴突高度相关,两种方法之间无显著差异。应用该方法揭示了不同损伤特异性的变化:脱位导致最大程度的轴突损失,而牵张导致最低的髓鞘与轴突面积比,表明轴突保留但严重脱髓鞘。所有损伤均导致轴突直径增加以及髓鞘厚度与轴突直径之比降低,提示髓鞘形成受到破坏。这些结果表明,髓鞘再生疗法可能对牵张性损伤最为有效,在这种损伤中保留的轴突使髓鞘再生至关重要,而轴突再生疗法可能更适合于轴突广泛损失的脱位性损伤。涉及轴突和髓鞘损伤的挫伤性损伤可能受益于神经保护和髓鞘再生策略的联合应用。这些发现突出了根据每种脊髓损伤类型的不同病理生理特征定制治疗方法以优化恢复结果的重要性。

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