Automated quantification of axonal and myelin changes in contusion, dislocation, and distraction spinal cord injuries: Insights into targeted remyelination and axonal regeneration
Xuan Li , Yuan He , Fangyao Chen , Xin Tong , Yunlong Fan , Yuzhe Langzhou , Jie Liu , Kinon Chen
{"title":"Automated quantification of axonal and myelin changes in contusion, dislocation, and distraction spinal cord injuries: Insights into targeted remyelination and axonal regeneration","authors":"Xuan Li , Yuan He , Fangyao Chen , Xin Tong , Yunlong Fan , Yuzhe Langzhou , Jie Liu , Kinon Chen","doi":"10.1016/j.brainresbull.2025.111193","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111193"},"PeriodicalIF":3.5000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Research Bulletin","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S036192302500005X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.