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, ) could be detected. In part two, significant vasospasm was induced in all hemorrhage groups . Analyzing microperfusion, a significant higher amount of perfused vessels could be detected , 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 and saline-treated group . The present study demonstrates the preconditioning impact of systemic intramuscular VEGF injection in animals after major stroke and induced severe vasospasm after SAH. 1. Introduction Cerebral vasospasm and delayed cerebral ischemia contribute the major part of secondary morbidity and mortality after severe subarachnoid hemorrhage (SAH) [1–5]. Despite the current treatment strategies, the rate of related permanent disability is estimated at 10% to 20% [6–9]. Vascular endothelial growth factor (VEGF) is involved in neurogenesis, inhibition of apoptosis, learning, and memory [10]. It can directly promote neuroprotection, but first of all VEGF is the main factor responsible for angiogenesis whereby an indirect neuroprotection is discussed. VEGF expression is increased during cerebral ischemia in humans and animals [11]. However, endogenous VEGF seems to be insufficient to protect the brain from ischemic injury completely. Interestingly, it could be shown that exogenous administrated VEGF induces angiogenic changes that result in a reduction of cerebral ischemic injury [12, 13]. For this reason VEGF was adopted as a potential novel therapeutic approach for the treatment of ischemic vascular disease, particularly in ischemic stroke [14–18]. The aim of the present experimental study was to examine the effect of systemic overexpression of VEGF prior to stroke and SAH with regard to cerebral infarction, vasospasm, and perfusion. 2. Material and Methods This study was carried out in
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