The impact of experimental preconditioning using vascular endothelial growth factor in stroke and subarachnoid hemorrhage

Abstract

Vascular endothelial growth factor (VEGF) stimulating angiogenesis was shown to be a potential novel therapeutic approach for the treatment of ischemic vascular diseases. The goal of the present study was to examine whether transfection of VEGF before occurrence of major stroke (part I) and cerebral vasospasm after experimental subarachnoid hemorrhage (SAH; part II) develops neuroprotective qualities. A total of 25 (part I) and 26 (part II) brains were analyzed, respectively. In part one, a significant reduction of infarct volume in the VEGF-treated stroke animals (43% reduction, P < 0.05) could be detected. In part two, significant vasospasm was induced in all hemorrhage groups (P < 0.02). Analyzing microperfusion, a significant higher amount of perfused vessels could be detected (P < 0.01), whereas no significant effect could be detected towards macroperfusion. Histologically, no infarctions were observed in the VEGF-treated SAH group and the sham-operated group. Minor infarction in terms of vasospasm-induced small lesions could be detected in the control vector transduced group (P = 0.05) and saline-treated group (P = 0.09). The present study demonstrates the preconditioning impact of systemic intramuscular VEGF injection in animals after major stroke and induced severe vasospasm after SAH.

Figure 1

Cresyl violet staining after 45 minutes of tMCAO and 24 h reperfusion time. (a) Distinct ischemic brain injury after i.m. injection with saline. (b) Attenuated ischemic brain injury after i.m. injection with VEGF. (c) Infarct volume in the three different groups in mm³.

Figure 2

(A) The brain cross-sectional vessel area in mm in the three SAH groups and the sham group. Displayed are the lowest, highest, and median values of brain cross-sectional vessel area (in mm), with upper (75%) and lower (25%) quartiles. (B) Digital subtraction angiography of rat number 11 demonstrating the internal carotid artery (b) to stapedial artery (a) ratio.

Figure 3

Minimum intense projection of cortical (without angiographic visible vessels) and major ROIs (with angiographic visible vessels): values of minimal intense projection are inversely correlated with the amount of perfused vessels. Displayed are the lowest, highest, and median pix² values, with upper (75%) and lower (25%) quartiles.

Figure 4

H&E stained section with cortical microinfarct in the cortical layers in a nontreated animal (a). At higher magnification mononuclear infiltration can be distinguished (b, arrow). Scale bar corresponds to 1000 μm (a) and 200 μm (b), respectively.