{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:58:20Z","timestamp":1790852300054,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Caspase-1 is a central mediator of canonical inflammasome signaling and drives neuroinflammatory injury through interleukin-1\u03b2 (IL-1\u03b2) and interleukin-18 (IL-18) maturation, gasdermin D (GSDMD)-mediated pyroptosis, and secondary inflammatory cascades. In spinal cord injury (SCI) and other neurologic disorders, experimental evidence links caspase-1 activation to blood\u2013spinal cord barrier (BSCB) or blood\u2013brain barrier (BBB) disruption, glial activation, neuronal and oligodendroglial injury, and worse functional outcomes. However, despite mechanistic rationale, the clinical role of caspase-1 as a biofluid biomarker remains incompletely defined. This review summarizes preclinical and clinical evidence regarding caspase-1 and inflammasome-associated proteins across cerebrospinal fluid (CSF), serum, plasma, and other biofluids, emphasizing SCI and translational neuroinflammation. Human studies suggest that inflammasome-associated markers may reflect acute inflammatory activity and injury severity, but direct caspase-1 measurement is limited by small cohorts, heterogeneous sampling windows, variable assay platforms, and inconsistent correlations with neurologic outcomes. Overall, caspase-1 remains a biologically plausible but not clinically established biomarker. Future studies should incorporate longitudinal sampling, standardized assays, paired measurement of IL-1\u03b2, IL-18, GSDMD, and other pyroptosis-related markers, and integration with imaging and functional outcomes. Such work may clarify whether caspase-1 can serve as a clinically actionable biomarker, prognostic indicator, or therapeutic monitoring target in SCI and related neuroinflammatory conditions.<\/jats:p>","DOI":"10.3390\/ijms27198802","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:25:44Z","timestamp":1790850344000},"page":"8802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Caspase-1 and Inflammasome Signaling in Spinal Cord Injury: Mechanistic Insights and Translational Gaps"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2812-6623","authenticated-orcid":false,"given":"Adonicah Y.","family":"Cummings","sequence":"first","affiliation":[{"name":"Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-9657","authenticated-orcid":false,"given":"Adham M.","family":"Khalafallah","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8725-771X","authenticated-orcid":false,"given":"Bhavjeet S.","family":"Sanghera","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6610-0288","authenticated-orcid":false,"given":"Isabella R.","family":"Chamma","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7497-3173","authenticated-orcid":false,"given":"Emily L.","family":"Errante","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7582-0877","authenticated-orcid":false,"given":"Adam S.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-2595","authenticated-orcid":false,"given":"Hisham F.","family":"Bahmad","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Dalton","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5460-8834","authenticated-orcid":false,"given":"Juan Pablo","family":"de Rivero Vaccari","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-627X","authenticated-orcid":false,"given":"S. Shelby","family":"Burks","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2012). Spinal cord injury facts and figures at a glance. J. Spinal Cord. Med., 35, 197\u2013198.","DOI":"10.1179\/1079026812Z.00000000063"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.13004\/kjnt.2024.20.e44","article-title":"Surgical and Neurointensive Management for Acute Spinal Cord Injury: A Narrative Review","volume":"20","author":"Kwon","year":"2024","journal-title":"Korean J. 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