Effect of hyperthermia on tight junctions of endothelial cells in the in vitro blood-brain barrier model and its molecular mechanism

Objective To discuss the effect of hyperthermia on tight junctions of the endothelial cells in the blood-brain barrier and explore the molecular mechanism. Methods An in vitro blood-brain barrier model was established by coculture of ECV304 and astrocytes. Transendothelial resistance (TER) of in vitro blood-brain barrier was determined by Millicell-ERS system. The morphological change of tight junctions of the endothelial cells in the in vitro blood-brain barrier was determined by the method of silver staining. The expression levels of zonula occluden 1 (ZO-1) and occludin were analyzed by means of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western bloting. Results After two hours at 43℃, the mean value of TER was decreased from (321.30± 58.59) Ω·cm2 to (65.67±6.02) Ω·cm2. The integrity of tight junctions was destroyed and the expressions of ZO-1 and occludin decreased significantly. Conclusions Hyperthermia can destroy the tight junctions of the endothelial cells in the in vitro blood-brain barrier. The expression decrease of ZO-1 and occludin induced by hyperthermia is one of the most important molecular mechanisms.