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Assessing the time course of molecular changes can provide insight into the progression of muscle wasting post\u2010SCI. The goals of this study were (1) to identify potential targets that may prevent the pathologic features of SCI in soleus muscles and (2) to establish therapeutic windows for treating these pathologic changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four\u2010month\u2010old Sprague\u2013Dawley male rats received T9 laminectomy (SHAM surgery) or severe contusion SCI. Hindlimb locomotor function was assessed weekly, with soleus muscles obtained 1\u00a0week, 2\u00a0weeks, 1\u00a0month and 3\u00a0months post\u2010surgery (<jats:italic>n<\/jats:italic>\u00a0=\u00a06\u20137 per group per timepoint). RNA was extracted from muscles for bulk RNA\u2010sequencing analysis (<jats:italic>n<\/jats:italic>\u00a0=\u00a03\u20135 per group per timepoint). Differentially expressed genes (DEGs) were evaluated between age\u2010matched SHAM and SCI animals. Myofiber size, muscle fibre type and fibrosis were assessed on contralateral muscles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SCI produced immediate and persistent hindlimb paralysis, with Basso\u2013Beattie\u2013Bresnahan locomotor scores remaining below 7 throughout the study, contributing to a progressive 25\u201350% lower soleus mass and myofiber atrophy versus SHAM (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 at all timepoints). Transcriptional comparisons of SCI versus SHAM resulted in 184 DEGs (1\u00a0week), 436 DEGs (2\u00a0weeks), 133 DEGs (1\u00a0month) and 1200 DEGs (3\u00a0months). Upregulated atrophy\u2010related genes included those associated with cell senescence, nuclear factor kappa B, ubiquitin proteasome and unfolded protein response pathways, along with upregulated genes that negatively influence muscle growth through the transforming growth factor beta pathway and inhibition of insulin\u2010like growth factor\u2010I\/Akt\/mechanistic target of rapamycin and p38\/mitogen\u2010activated protein kinase signalling. Genes associated with extracellular matrix (ECM), including collagens, collagen crosslinkers, proteoglycans and those regulating ECM integrity, were enriched within upregulated DEGs at 1\u00a0week but subsequently downregulated at 2\u00a0weeks and 3\u00a0months and were accompanied by &gt;50% higher ECM areas and hydroxyproline levels in SCI muscles (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Myofiber remodelling genes were enriched in upregulated DEGs at 2\u00a0weeks and 1\u00a0month and were downregulated at 3\u00a0months. Genes that regulate neuromuscular junction remodelling were evident in muscles post\u2010SCI, along with slow\u2010to\u2010fast fibre\u2010type shifts: 1 week and 2 weeks SCI muscles were composed of 90% myosin heavy chain (MHC) type I fibres, which decreased to only 16% at 3\u00a0months and were accompanied by 50% fibres containing MHC IIX (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Metabolism genes were enriched in upregulated DEGs at 1\u00a0month and were further enriched at 3\u00a0months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results substantiate many known pathologic features of SCI\u2010induced wasting in rat skeletal muscle and identify a progressive and dynamic transcriptional landscape within the post\u2010SCI soleus. Future studies are warranted to consider these therapeutic treatment windows when countering SCI muscle pathology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13476","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T06:03:59Z","timestamp":1716185039000},"page":"1309-1323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transcriptomics reveals transient and dynamic muscle fibrosis and atrophy differences following spinal cord injury in rats"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-9184","authenticated-orcid":false,"given":"Hui Jean","family":"Kok","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology College of Health and Human Performance, University of Florida  Gainesville FL USA"},{"name":"Research Service, Malcolm Randall Department of Veterans Affairs Medical Center North Florida\/South 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