The Role of Circulating Tight Junction Proteins in Evaluating Blood Brain Barrier Disruption following Intracranial Hemorrhage.

Xiaoyang Jiao,Xiaolan Chang,Yazhen Li,Qingdong Xie,Mengya Si,Ping He,Zhicheng Fan,Dongyang Huang

doi:10.1155/2015/860120

Xiaoyang Jiao, Xiaolan Chang + Show 6 more

Open Access

https://doi.org/10.1155/2015/860120

Copy DOI

Journal: Disease markers	Publication Date: Jan 1, 2015
Citations: 84	License type: CC BY 3.0

Affiliation: Shantou University Medical College

Abstract

Brain injury after intracranial hemorrhage (ICH) results in significant morbidity and mortality. Blood brain barrier (BBB) disruption is a hallmark of ICH-induced brain injury; however, data mirroring BBB disruption in human ICH are scarce. The aim of this study was to assess the significance of circulating biomarkers in evaluating BBB disruption after ICH. Twenty-two patients with ICH were recruited in this study. Concentrations of the tight junction proteins (TJs) Claudin-5 (CLDN5), Occludin (OCLN), and zonula occludens 1 (ZO-1) and vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were measured by using enzyme-linked immunosorbent assay in serum and cerebrospinal fluid (CSF) samples obtained from patients with ICH. The white blood cell (WBC) count in blood and CSF, albumin (ALB) levels in the CSF (ALBCSF), and the BBB ratio were significantly higher in the ICH than in controls (p < 0.05). Significantly higher levels of CLDN5, OCLN, ZO-1, MMP-9, and VEGF in CSF were observed in the ICH group; these biomarkers were also positively associated with BBB ratio (p < 0.05). Our data revealed that circulating TJs could be considered the potential biomarkers reflecting the integrity of the BBB in ICH.

Highlights

Spontaneous intracranial hemorrhage (ICH) results in significant morbidity and mortality, thirty-day case fatality rates which range from 40% to 50% in most studies [1,2,3]
Blood brain barrier (BBB) disruption is a hallmark of ICH-induced brain injury, which contributes to edema formation, the influx of leukocytes, and the entry of potentially neuroactive agents into the perihematomal brain [7,8,9]
The expressions of ZO1 and OCLN were significantly decreased after subarachnoid hemorrhage (SAH) [15], and degrading zonula occludens 1 (ZO-1) and OCLN in endothelial tight junction can facilitate capillary leakage, which is responsible for the increase in BBB permeability after SAH [16]

Summary

Introduction

Spontaneous intracranial hemorrhage (ICH) results in significant morbidity and mortality, thirty-day case fatality rates which range from 40% to 50% in most studies [1,2,3]. The BBB inhibits transcellular or paracellular passage of molecules across it by an elaborate network of complex tight junctions between the endothelial cells [11]. Tight junction proteins (TJs) are the main components of the BBB [12]. Claudin-5 (CLDN5), ZO-1, and Occludin (OCLN) are the main components of TJs in brain endothelial cells to maintain the BBB integrity. CLDN5 knockout mice presented increased BBB permeability [13]; on the contrary, inhibiting decreased expression of CLDN5 has been shown to reduce brain edema and hemorrhagic transformation [14]. The expressions of ZO1 and OCLN were significantly decreased after subarachnoid hemorrhage (SAH) [15], and degrading ZO-1 and OCLN in endothelial tight junction can facilitate capillary leakage, which is responsible for the increase in BBB permeability after SAH [16]. Presence of TJs in the neurovascular unit is one likely component of the brain’s armamentarium against hemorrhage; the role of TJs in mirroring the BBB disruption in human ICH is scarce

Objectives

Methods

Results

Conclusion