Association between serum netrin-1 levels and early neurological deterioration after acute ischemic stroke

Abstract

Background and purposes: Experimental studies demonstrated that netrin-1 (NT-1) has anti-inflammatory, tissue regeneration, and immune modulation properties. We aimed to discern the utility of NT-1 as a biomarker for assessing the risk of early neurological deterioration (END) after ischemic stroke.

Methods: This was a prospective study enrolling ischemic stroke patients with symptoms onset <24 h. Serum NT-1 concentrations were measured at admission. The National Institutes of Health Stroke Scale increased by ≥2 points and ≥4 points during the first 72 h after admission and was defined as END2 and END4, respectively.

Results: The study included 268 patients (146 men and 122 women) with a mean age of 63.0 ± 9.6 years. The median NT-1 concentrations were 466.4 pg/ml (interquartile range, 341.4-589.2 pg/ml). During the initial 72 h after admission, END2 was found in 83 (31.0%) patients, and END4 was observed in 48 (17.9%) subjects. After adjusted for potential confounders, multivariate analysis indicated that decreased NT-1 levels is an independent predictor for END2 [odds ratio (OR) 0.62, 95% confidence interval (CI) 0.46-0.84, p < 0.001) and END4 (OR 0.53, 95% CI 0.36-0.76, p < 0.001). Similar results were found when the NT-1 levels were analyzed as a categorical variable. Furthermore, restricted cubic spline analysis showed a linear association between NT-1 concentrations and the risk of END (END2, p = 0.006 for linearity; END4, p < 0.001 for linearity).

Conclusions: Our results suggest that decreased NT-1 levels were significantly associated with a higher risk of END after ischemic stroke.

Keywords: acute ischemic stroke; biomarker; early neurological deterioration; netrin-1; restricted cubic spline.

Figure 1

(A,B) Association was fitted with a restricted cubic spline with 3 knots (at 5th, 50th, and 95th percentiles) adjusted for demographic characteristics, hypertension, baseline NIHSS score, baseline glucose levels, and hyper-sensitive C-reactive protein levels. The reference point for netrin-1 levels is 315.5 pg/ml (lowest quantiles of netrin-1 levels). CI, confidence intervals; OR, odds ratio.