Neuroprotective effects of VEGF administration after focal cerebral ischemia/reperfusion: Dose response and time window

Administration of vascular endothelial growth factor (VEGF) has been shown to increase cerebral blood flow and reduce neurological damage after experimental ischemic brain injury. The purpose of this study was to examine the optimal dose and time window for the neuroprotective effect of VEGF when administrated after focal ischemia/reperfusion injury in rabbits. Focal cerebral ischemia/reperfusion was induced by the middle cerebral artery occlusion (MCAO) method. In a dose response experiment, low (1.25 ng/μL), middle (2.5 ng/μL) and high (5.0 ng/μL) doses of VEGF were administered 2 h after MCAO by the route of perifocal region. The VEGF at a dose of middle (2.5 ng/μL) displayed excellent effects on neuroprotective efficacy for focal cerebral ischemia/reperfusion injury. In another experiment, 2.5 ng/μL VEGF was administered at times varying from 2 to 8 h after MCAO. Infarct volume, water content and neurological deficits were significantly reduced when VEGF was given at 2 and 3 h after injury. The protective effect was less when the same dose was given at the later times. Thus, the present findings indicated that VEGF reduced ischemic neuronal danger with a therapeutic time window within the first 3 h of transient MCAO and may be useful in the treatment of acute ischemic stroke in humans.

► We examine the optimal dose of VEGF when administrated after stroke.
► We examine the neuroprotective time window of VEGF.
► The VEGF at middle dose (2.5 ng/μL) displayed excellent neuroprotective effects.
► VEGF treatment confers a large therapeutic window of at least 3 h of ischemia.
► VEGF may be useful in the treatment of ischemic stroke in humans.