Conclusion
The aforementioned findings demonstrated that SAL could protect BBB integrity through Notch-ITGB1 signaling path in CSVD, which indicated that SAL could be a potential medicine candidate for CSVD treatment.
Methods
We established a rat model of SHR via 2-vessel gradual occlusion (SHR-2VGO) to mimic the CSVD. Subsequently, the MRI, pathomorphism, as well as Morriss water maze test were conducted to determine CSVD-related indicators. 8 weeks post-surgery, animals were randomly administered SAL, DAPT, ATN161 or saline.The aim was to explore the protective effects of SAL in CSVD as well as its possible mechanism.
Results
Here we found that SAL could attenuate cerebral hypoperfusion-induced BBB disruption, promote the pro-angiogenesis through enhancing the cell budding. Further investigations demonstrated that SAL could significantly increase the expression of Notch1, Hes1, Hes5, and ITGB1. In addition, we confirmed that SAL could activate Notch signal path, and then up-regulate ITGB1 to promote pro-angiogenesis and thus protect BBB from disruption.