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Figure 3. VEGF protects against ischemia and induces BBB leakage by activating the PI3K/Akt pathway. In ischemic brains of WT mice, both Akt and ERK-1/-2 activities are low, whereas p38 and JNK-1/-2 activities are high. As a consequence, ischemic neurons die and BBB remains functional. In mice constitutively expressing human VEGF (V1tg), on the other hand, Akt and ERK-1/-2 pathways are activated, whereas p38 and JNK-1/-2 pathways are inhibited. Thereby, ischemic neurons remain viable, at the expense of an enhanced BBB permeability. Inhibition of the PI3K/Akt pathway with Wortmannin completely abolishes the tissue protection induced by VEGF, at the same time reversing BBB function.
