Caspase-1 and Inflammasome Signaling in Spinal Cord Injury: Mechanistic Insights and Translational Gaps

Abstract

Caspase-1 is a central mediator of canonical inflammasome signaling and drives neuroinflammatory injury through interleukin-1β (IL-1β) 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–spinal cord barrier (BSCB) or blood–brain 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-1β, 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.