Hypertonic saline alleviates experimentally induced cerebral oedema through suppression of vascular endothelial growth factor and its receptor VEGFR2 expression in astrocytes

摘要

Background Cerebral oedema is closely related to the permeability of blood–brain barrier, vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) all of which are important blood–brain barrier (BBB) permeability regulatory factors. Zonula occludens 1 (ZO-1) and claudin-5 are also the key components of BBB. Hypertonic saline is widely used to alleviate cerebral oedema. This study aimed to explore the possible mechanisms underlying hypertonic saline that ameliorates cerebral oedema effectively. Methods Middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and of oxygen–glucose deprivation model in primary astrocytes were used in this study. The brain water content (BWC) was used to assess the effect of 10?% HS on cerebral oedema. The assessment of Evans blue (EB) extravasation was performed to evaluate the protective effect of 10?% HS on blood–brain barrier. The quantification of VEGF, VEGFR2, ZO-1 and claudin-5 was used to illustrate the mechanism of 10?% HS ameliorating cerebral oedema. Results BWC was analysed by wet-to-dry ratios in the ischemic hemisphere of SD rats; it was significantly decreased after 10?% HS treatment ( P Conclusions The results suggest that 10?% HS could alleviate cerebral oedema possibly through reducing the ischemia induced BBB permeability as a consequence of inhibiting VEGF–VEGFR2-mediated down-regulation of ZO-1, claudin-5.