Figure 6.

Summary of findings. Inhibition of HSP90 using 17-AAG improves blood–brain barrier integrity. Our results revealed that preincubation with 17-AAG mitigated the reduction of TEER values caused by the KCl pulse on the monolayer of bEnd.3 cells. The increased uptake of ¹⁴C-sucrose across the same endothelial monolayer induced by the KCl pulse was significantly attenuated after preincubation with the same HSP90 inhibitor. Pre-exposure to 17-AAG significantly reduced the transient BBB leak after CSD induced by cortical KCl injection as determined by in situ brain perfusion in female rats. The pharmacological blockade of HSP90 increased the detection of claudin 5 in cortex and PAG, which can play a part in the effect of HSP90 inhibition to protect BBB integrity.