Ischemic stroke activates the VE-cadherin promoter and increases VE-cadherin expression in adult mice

Abstract

Endothelial cells (ECs) are a key component of the blood-brain barrier (BBB). Healthy ECs in the BBB form inter-endothelial junctions, including adherens junctions (AJs). Under pathological conditions, such as after ischemic stroke, the BBB may be functionally compromised. However, gene and protein expression patterns involving endothelial AJs have not been well studied. Because expression levels of endothelial AJs are considered to be related to BBB functionality, we investigated the expression pattern of a representative endothelial AJ marker, VE-cadherin, in healthy and diseased mice. We first examined the expression of VE-cadherin in developing mouse brains. In addition, using a mouse model of cerebral infarction, we investigated the expression pattern of VE-cadherin in pathologic brains. Furthermore, using the Cre-LoxP system, we established a strain of mice expressing yellow fluorescent protein (YFP) under the control of the VE-cadherin promoter and investigated the expression pattern of YFP-expressing ECs in developing and pathologic murine brains. VE-cadherin protein and YFP expression driven by the VE-cadherin promoter both showed that VE-cadherin expression was weak during embryonic stages, followed by a steady increase postnatally, which then decreased during adulthood. However, following ischemic stroke, imunohistochemistry of VE-cadherin demonstrated an upregulation in ECs within ischemic regions, concomitant with YFP upregulation. These findings reveal that ischemic stroke activates the VE-cadherin promoter and increases VE-cadherin protein expression, which suggests that endothelial VE-cadherin is involved in the reconstruction of the BBB following ischemic stroke.