Effects of VEGF-A in cerebral stroke–timeline. Before stroke onset, the upregulation of VEGF-A (large arrow labelled VEGF-A), preconditioning or exercise decreases the risk of stroke as well as the outcome after stroke. The latter is, at least partly, due to the increased formation of collateral (angiogenic effects) and direct neuroprotective effects of VEGF-A. In the acute phase (0–24 h after stroke onset), the systemic administration of VEGF-A at levels leading to angiogenesis, or the intrinsic upregulation of VEGF-A lead to a leaky BBB and corresponding detrimental effects. The application of low non-angiogenic doses (e.g., via a cerebral artery) as well as the intraventricular or topical application of VEGF-A have a neuroprotective effect, even in the acute phase. In the later phase (>24 h) after stroke, increased levels of VEGF-A decrease stroke-induced neural damage.