Neuroprotective Effects of Nanocurcumin in Spinal Cord Injury: Modulation of Inflammatory and Inflammasome-Associated Signaling in an Integrated In Vivo , In Silico , and Machine-Learning Study

Spinal cord injury (SCI) triggers secondary neuroinflammatory and inflammasome-associated responses that contribute to tissue damage and functional impairment. This study evaluated nanocurcumin in experimental SCI using integrated experimental, computational, and exploratory machine-learning approaches. Adult male Wistar rats were allocated to Sham, SCI, or SCI + nanocurcumin groups. SCI was induced by T6 contusion, and nanocurcumin (50 mg/kg, intraperitoneally) was administered every 12 hours for 72 hours. Functional, histological, molecular, and inflammatory outcomes were assessed using BBB scoring, Luxol Fast Blue staining, immunofluorescence, RT-qPCR, and ELISA. SCI impaired locomotor function and myelin integrity and increased inflammasome-associated and inflammatory markers. Nanocurcumin significantly improved BBB scores, increased the LFB-positive myelinated area, and attenuated these molecular alterations. Tissue IL-1β, IL-18, HMGB1, and TLR4 levels were also reduced following nanocurcumin treatment compared with untreated SCI. Correlation and hierarchical clustering analyses demonstrated coordinated molecular–functional associations and separation of SCI from control and treated profiles. Exploratory Random Forest/SHAP analyses highlighted NF-κB, Caspase-1, NOX2, and NLRP3 as influential variables for group discrimination. Docking predicted favorable curcumin–target interactions, while MD simulations supported distinct conformational behavior of selected complexes. Overall, nanocurcumin was associated with attenuated inflammatory and inflammasome-associated responses and improved early functional and histological outcomes following SCI.