Figure 2. The PI3K/Akt pathway mediates VEGF’s neuroprotective function and BBB permeability. Data from wt and V1tg mice that were either untreated or i.c.v. treated with DMSO or DMSO/Wortmannin. Note that LDF during ischemia does not differ between groups (A). Assessments of infarct vol. (B) and neurological deficits (C) reveal that human VEGF significantly reduces brain injury and ameliorates postischemic recovery. Brain swelling (D) is not influenced by human VEGF, whereas IgG extravasation (E) is moderately increased, indicating that VEGF expression promotes BBB leakage. Note that the neuroprotective effects of VEGF are reversed by PI3K/Akt inhibition (B, C), while brain swelling (D) and BBB permeability (E) are reduced, despite the exacerbation of brain infarcts. These data demonstrate that the PI3K/Akt pathway is responsible for VEGF’s neuroprotective function and vascular leakage. Values are means ± SD (n=5–11 animals/ group). *P < 0.05 compared with WT mice; ^#P < 0.05 compared with V1tg mice receiving DMSO.