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Systemic muscle wasting caused muscle weakness, affected fast type 2 myofibers preferentially, and became exacerbated after high (T3) compared with low (T9) thoracic paraplegia, indicating lesion level\u2013dependent (\u201cneurogenic\u201d) mechanisms. The wasting of nonparalyzed muscle and its rapid onset and severity beyond what can be explained by disuse implied unknown systemic drivers. Muscle transcriptome and biochemical analysis revealed a glucocorticoid-mediated catabolic signature early after T3 SCI. SCI-induced systemic muscle wasting was mitigated by (i) endogenous glucocorticoid ablation (adrenalectomy) and (ii) pharmacological glucocorticoid receptor (GR) blockade and was (iii) completely prevented after T3 relative to T9 SCI by genetic muscle-specific GR deletion. These results suggest that neurogenic hypercortisolism contributes to a rapid systemic and functionally relevant muscle wasting syndrome early after paraplegic SCI in mice.<\/jats:p>","DOI":"10.1126\/scitranslmed.adh2156","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T13:58:11Z","timestamp":1703080691000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Lesion level\u2013dependent systemic muscle wasting after spinal cord injury is mediated by glucocorticoid signaling in mice"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3809-1951","authenticated-orcid":true,"given":"Markus E.","family":"Harrigan","sequence":"first","affiliation":[{"name":"Department of Neurology, Spinal Cord Injury Division (Paraplegiology), College of Medicine, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Medical Scientist Training 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