On the other hand, the scHSP-induced downregulation of VEGFR2 and ERK1/2 activation in BLECs exposed to OGD conditions might have a beneficial effect, considering that hypoxia-driven VEGF-A production is the main mechanism inducing BBB leakage (Ma et al. 2012) and that MAPK activation plays a key role in vascular injury induced by ischemia (Narasimhan et al. 2009; Maddahi and Edvinsson 2010). Here, MAPK3 is linked to ischemia.