Correlation between serum tight junction proteins with blood brain barrier integrity in ischemic stroke patients

Abstract

Blood brain barrier (BBB) breakdown is a proposed mechanism for ischemic stroke (IS). Platelet-derived growth factor B (PDGFB) and tight junction (TJ) associated proteins; zonula occluden-1 (ZO-1) and claudin-5 (CLDN5), play fundamental roles in keeping BBB integrity. The aim of the present work is to investigate the impact of some modifiable stroke risk factors on serum levels of CLDN5, ZO-1and PDGFB, as non-invasive markers for BBB integrity. The present study was performed on 186 IS patients. Patients were classified into two groups; Group I: small vessel disease (SVD) patients; n= 114, and Group II: large vessel disease (LVD) patients; n= 72. Serum levels of ZO-1, CLDN5 and PDGFB were measured using human ELISA kits. Ischemic heart disease (IHD) was significantly (p<0.05) associated with decreased serum levels of ZO-1 and PDGFB in LVD patients, along with decreased levels of ZO-1 and CLDN5 in SVD patients. Smoking could not be associated with any reliable differences in any of the studied markers. Diabetes mellitus (DM) was significantly (p<0.05) associated with decreased levels of ZO-1 in both LVD and SVD patients, while hypertension (HTN) was significantly (p<0.05) associated with decreased levels of ZO-1 only in SVD patients. IHD, DM and HTN are significantly associated with decreased levels of serum markers of BBB integrity, however, their impacts differ according to stroke subtype. Defining extent of BBB injury associated with each risk factor could both help predict patients’ prognosis and serve as a useful tool in making individualized treatment plans.