The Role of Fibrinogen in Mediating NGAL-Associated Neuronal Damage in Acute Ischemic Stroke: A Moderated Mediation Analysis.

BACKGROUND: Both neutrophil gelatinase-associated lipocalin (NGAL) and fibrinogen are involved in the inflammation in acute ischemic stroke (AIS), but the interaction among them is unknown. Clarifying this issue will contribute to a better understanding of the mechanisms of injury in AIS. This study aimed to explore the association between NGAL, fibrinogen and neuronal damage in AIS. METHODS: This study is a cross-section study. One hundred ninety-six successively hospitalized AIS patients in Renji Hospital in China between January 1, 2023, and May 31, 2023, were included. Circulating NGAL and fibrinogen were measured, and neuron-specific enolase (NSE) was detected to evaluate central neuronal damage. All data were analyzed by linear curve fitting analysis, multiple linear regression analysis, and moderated mediation analysis, respectively. RESULTS: There are linear relationships between log2-transformed NGAL, NSE, and fibrinogen, respectively. The β (95%) for the positive association between log2-transformed NGAL and NSE was 2.24 (1.15-3.32, p < 0.01), between log2-transformed NGAL and fibrinogen was 0.37 (0.19-0.56, p < 0.01), and between fibrinogen and NSE was 1.16 (0.48-1.85, p < 0.01) adjusting for potential confounders. These associations remained consistent in sensitivity analysis and hierarchical analysis. Increased fibrinogen significantly (p < 0.01) mediated 14.28% of log2-transformed NGAL-associated increased NSE risk. CONCLUSION: The NGAL levels were associated with NSE, and the NGAL-associated neuronal damage might be partially mediated by fibrinogen, suggesting that the inflammatory response among NGAL, fibrinogen, and NSE should be intervened to reduce neuronal damage after ischemic stroke. Further animal experiments are needed to clarify their specific mechanisms and precise relationships.