The dose-effectiveness of intranasal VEGF in treatment of experimental stroke

The aim of the present study was to assess the dose-effectiveness of intranasal (IN) vascular endothelial growth factor (VEGF)in the treatment of experimental stroke. Sprague-Dawley rats were randomized into four groups as IN low (100 mu g/ml), IN middle (200 mu g/ml) and IN high (500 mu g/ml) VEGF-treated group, and IN saline-treated group (n = 12), given recombinant human VEGF 165 or saline intranasally. Focal cerebral ischemia was induced by transient (90 min) middle cerebral artery occlusion (MCAO) method. Behavioral neurological deficits were assessed 1, 7 and 14 d after the onset of MCAO. Rats were sacrificed at 14 d, the brain sections were stained and an image analysis system was used to calculate the infarct volume. Microvessels were labeled by FITC-dextran and the segment lengths, diameters and number of microvessels were measured by Image Pro-Plus Version 6.0 software. Fourteen days post MCAO, infarct volume significantly reduced (P < 0.01) in rats which received the middle dose of IN VEGF when compared to IN saline. And middle dose of VEGF significantly improved behavioral recovery (P < 0.01). No significant difference in the behavioral recovery and infarct volume was observed between the saline-treated group and the low or high VEGF-treated groups (P > 0.05). Compared to IN saline, middle and high doses of VEGF significantly increased the segment length, diameter and number of microvessels (P < 0.01). No significant difference in the segment length, diameter and number of microvessels was observed between the IN saline-treated group and the low VEGF-treated group (P > 0.05). The middle dose of IN VEGF was most effective on reducing infarct volume, improving behavioral recovery and enhancing angiogenesis in stroke brain, which can be used in the following treatments to further evaluate the effect of VEGF. (C) 2009 Elsevier Ireland Ltd. All rights reserved.