Concentration‐Dependent Increase in the Expression of Junctional Adhesion Molecule‐A in Brain Microvascular Endothelial Cells in Response to Proinflammatory Cytokines and Hyperthermic Decrease in the Expression of Vascular Endothelial Cadherin in The

ABSTRACT Objective The mechanisms underlying therapeutic hypothermia, which protects neurons after severe brain damage, are not completely understood. Based on a previous study, hypothermia reduced the release of tumor necrosis factor (TNF)‐α and interleukin (IL)‐17. Meanwhile, hyperthermia promoted the release of TNF‐α and IL‐17. Leukocyte transmigration via the endothelium is mediated by endothelial cell junctional molecules, such as junctional adhesion molecule (JAM)‐A and vascular endothelial cadherin (VE‐cadherin), positively and negatively, respectively. In the ischemic brain, the diapedesis of leukocytes into the tissues results in enhanced postischemic brain inflammation and intensified brain injury. The current study aimed to evaluate the mechanisms underlying this treatment by assessing the effects of TNF‐α and IL‐17 on brain microvascular endothelial cell (BMVEC) junctional molecule and the effects of hypothermia and hyperthermia on its expression. Methods The expression of JAM‐A and VE‐cadherin, which are BMVEC junctional molecules, was measured at the protein level via immunocytochemistry. Results TNF‐α and IL‐17 increased the expression of JAM‐A in BMVECs in a concentration‐dependent manner. Compared with normothermia, hypothermia did not affect the expression of JAM‐A and VE‐cadherin in BMVECs stimulated with TNF‐α or IL‐17. Meanwhile, hyperthermia reduced the basal expression of VE‐cadherin in BMVECs, with this expression being further reduced by stimulation with IL‐17. Conclusions The hypothermic suppression of TNF‐α and IL‐17 release may decrease JAM‐A expression in BMVECs. Meanwhile, hyperthermia itself may decrease VE‐cadherin expression in BMVECs. The former may contribute to suppressing, while the latter may promote, leukocyte extravasation.