Elevated Serum Levels of CXC Chemokine Ligand-12 Are Associated with Unfavorable Functional Outcome and Mortality at 6-Month Follow-up in Chinese Patients with Acute Ischemic Stroke

Abstract

The aim of this study was to examine whether the circulating CXC chemokine ligand-12 (CXCL12) level can predict a 6-month outcome in Chinese patients with acute ischemic stroke (AIS). In a prospective study, CXCL12 levels were measured on admission in the serum of 304 consecutive patients with AIS. The prognostic value of CXCL12 to predict the functional outcome and mortality within 1 year was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. A receiver operating characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in predicting functional outcome and mortality. Patients with an unfavorable outcome and non-survivors had significantly increased CXCL12 levels on admission (P < 0.0001 and P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that CXCL12 (≥12.4 ng/mL; third quartile) was an independent predictor of functional outcome (odds ratio [OR] = 8.81; 95 % confidence interval [CI] 4.92-24.79) and mortality (OR = 10.15; 95 %CI 2.44-27.98). The area under the receiver operating characteristic curve of CXCL12 was 0.84 (95 % CI 0.76-0.92) for functional outcome and 0.87 (95 % CI 0.80-0.93) for mortality. Circulating CXCL12 serum levels at admission is a useful and complementary biomarker to predict functional outcome and mortality 6 months after acute ischemic stroke.

Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models

“…Arac described that interleukin 6 and chemokine (C-C motif) ligand 7, contributed to stroke pathology [ 23 ]. A six month follow up study in Chinese stroke patients indicated the association between the high levels of CXC chemokine ligand 12 and unfavorable outcomes and mortality [ 24 ]. A blockade of CXCR1/2 chemokine receptors and ELR CXC chemokine antagonism protected mice in ischemic stroke [ 25 , 26 ].…”

CCL23: a new CC chemokine involved in human brain damage

“…Similar to CCL23, the abovementioned CXCL12 and CC chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein 1, increase in circulation after stroke, and higher blood levels indicate poor long-term outcome and stroke recurrence [30][31][32]. These results support the hypothesis that specific pro-inflammatory chemokines may potentially reflect the stroke-related inflammatory response, which is a key factor predicting patient outcome, and high circulating CCL23 levels during the first days after stroke may influence the disease course, as well as patient prognosis and survival.…”

Evaluation of Gene Therapy as an Intervention Strategy to Treat Brain Injury from Stroke

“…Adenoviral or rAAV gene delivery of CXCL-12 into mice and rats, administered from 3 days pre-ischemia to 7 days post-ischemia reduced brain atrophy, maintained myelin sheath integrity, increased oligodendrocyte progenitor cell proliferation and migration, and the promotion of angiogenesis ( Yoo et al, 2012 ; Li et al, 2014 , 2015 ). Further contrast is seen in clinical studies, with a positive correlation between increased serum CXCL-12 levels and poor outcome in stroke patients in a Chinese cohort, but increases in CXCL-12 serum levels in patients transplanted with autologous mesenchymal stem cells correlating to improved outcome ( Lee et al, 2010 ; Liu et al, 2015 ; Cheng et al, 2016 ).…”