Systemic Inflammation and Central Neuronal Damage: The Relationship Between Neutrophil‐to‐Lymphocyte Ratio and Neuron‐Specific Enolase in Acute Ischemic Stroke

Background and Purpose The systemic inflammatory response, quantified by the neutrophil‐to‐lymphocyte ratio (NLR), and central neuronal injury, reflected by serum neuron‐specific enolase (NSE), are implicated in the pathogenesis of acute ischemic stroke (AIS). However, the association between these two processes remains inadequately explored at the population level. This study aimed to investigate the relationship between NLR and neuronal injury via circulating biomarkers in AIS. Methods In this cross‐sectional study, 4272 consecutively enrolled AIS patients from a single center in China were included. Serum NSE levels were measured, and NLR was calculated from peripheral blood counts and log₂‐transformed for analysis. The association between log 2 (NLR) and elevated NSE (≥ 16.3 μg/L) was evaluated using multivariable logistic regression models adjusted for potential confounders, smooth curve fitting, and cumulative incidence analysis. Results Serum NSE levels and the prevalence of high NSE both increased significantly across tertiles of log 2 ‐transformed NLR (both p < 0.001). A linear relationship was observed between log 2 (NLR) and NSE levels. After full adjustment for covariates, each unit increase in log 2 (NLR) was associated with a 38% increased risk of high NSE (OR = 1.38, 95% CI: 1.25–1.53, p < 0.001). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.62 (95% CI: 0.60–0.64) for log 2 (NLR) in discriminating patients with high NSE. Conclusion Elevated NLR is independently associated with higher levels of serum NSE in patients with AIS, supporting a link between systemic inflammation and the extent of central neuronal injury. These findings provide epidemiological evidence for an interaction between circulatory inflammatory responses and brain damage following ischemic stroke. However, due to the cross‐sectional design, causality cannot be inferred, and the modest discriminatory ability of NLR limits its potential as a standalone clinical marker.