Endothelin-1 overexpression leads to blood-brain barrier disruption, more brain edema and increased aquaporin 4 expression in astrocytic processes after experimental stroke

摘要

Under normal condition endothelin-1 (ET-1) is expressed bycerebral endothelial cells. However, increased level of ET-1 wasobserved in both astrocytes and endothelial cells after experimentalischemic stroke and hypoxia/ischemia, suggesting a potentialrole of astrocytic and endothelial ET-1 in ischemic braininjury. Previously, we reported that transgenic mice over-expressingET-1 in astrocytes (GET-1 mice) displayed increased cerebralinfarct size and more severe neurological deficits upon focal cerebralischemia induced by middle cerebral artery occlusion(MCAO). However, the mechanism behind astrocytic ET-1 onischemia-induced brain injury was not clear. Here, we report thatGET mice showed lower occludin levels and increased Evans blueextravasation, suggesting increased blood-brain barrier (BBB)breakdown in GET-1 mice after MCAO. GET-1 mice also displayedincreased brain swelling and brain water content together with decreased occludin and up-regulated aquaporin 4 expression.These results suggested that increased astrocytic ET-1 resultedin BBB disruption leading to increased formation of brainedema and swelling, infarct and neurological deficits and thereforeimposed adverse effects on brain injury after focal cerebralischemia.Acknowledgement: Supported by Research Grants Counciland Area of Excellence from University Grants Council of HongKong (AoE/B-15/01).