Kinetic and inhibitory profiling of serum MMP-9 in acute spinal cord injury: neurochemical links to injury severity and neuroinflammation.

BACKGROUND: Spinal cord injury (SCI) is a devastating neurological condition characterized by pronounced neuroinflammation and progressive neurodegeneration. Matrix metalloproteinase-9 (MMP-9) has emerged as a crucial regulator of inflammatory cascades, yet its role as a predictive biomarker and enzyme kinetic behaviour persists ambiguous. MMP-9 has recently become a key and seemingly distinct contributor to brain physiology and pathology. The local and time-constrained nature of MMP-9 actions may be the reason why it is so specific, even when it is released into the brain by cells of different types, such as neurons, glia, and leukocytes. OBJECTIVES: The aims of the study were to examine the enzymatic kinetics of MMP-9 in acute spinal cord injury, determine how MMP-9-inhibitor-I inhibits MMP-9, and correlate MMP-9 levels with the severity of injury and neuroinflammatory indicators to explore the inhibitory response of MMP-9 inhibitor-I in vitro and evaluate the potential relevance of MMP-9 as a severity-associated biomarker and experimental inhibitory target in acute SCI. METHODS: In this cross-sectional study, 160 patients with confirmed acute SCI were stratified according to the American Spinal Injury Association Impairment Scale into Mild/Moderate and severe groups. Serum concentrations of MMP-9, C-reactive protein (CRP), creatine kinase-BB (CK-BB), and routine biochemical markers were quantified. Multivariable regression analyses were performed to adjust for confounding variables, and receiver operating characteristic (ROC) curve analysis was used to assess the discriminatory performance of MMP-9. RESULTS: MMP-9 levels were significantly elevated in patients with severe SCI compared with Mild/Moderate injury (p < 0.001) and showed a strong positive correlation with injury severity (r = 0.755, p < 0.001) and positive correlation with CK-BB levels (r = 0.223, p = 0.047). MMP-9 remained independently associated with SCI severity in the adjusted model. ROC analysis demonstrated excellent discriminatory performance (AUC = 0.942; 95% CI: 0.878-1.000). Enzymatic kinetic analysis suggested higher apparent catalytic activity in severe cases, Inhibition studies showed a kinetic pattern consistent with non-competitive inhibition by MMP-9 inhibitor-I.