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.

HIF‐1α Mediates Isoflurane‐Induced Vascular Protection in Subarachnoid Hemorrhage

“… 8 Another possibility – though not mutually exclusive from HIF-1 α 's effects on vascular ECs – is that one or more HIF-1 α -driven secreted proteins exert paracrine protective effects on neighboring cells. Potential target molecules here include iNOS (which, as mentioned above, has been implicated in the vascular protection afforded by isoflurane in cerebral ischemia 45 ) and vascular endothelial growth factor (which has been previously linked to vasospasm protection 56 ). Third is the neurovascular protection afforded by postconditioning present across SAH model systems (endovascular perforation, cisterna magna injection, prechiasmatic injection), species (lissencephalic vs. gyrencephalic), gender (male vs. female), age (young vs. old), comorbidities (hypertension, diabetes, etc.…”

Evaluation of Vascular Endothelial Growth Factor A and Selected Parameters of Coagulation and Fibrinolysis in a Group of Patients with Subarachnoid Haemorrhage

“…In this study, by analysing the cerebrovascular microperfusion, vasospasm induction was observed immediately after the SAH incident. The increase in the concentration of VEGF-A was also observed, which is associated with neoangiogenesis increase in cerebral vessels [29].…”

“…So far two receptors specific for VEGF: VEGFR-1 (Flt1) and VEGFR-2 (KDR/Flt-1), have been identified. Most effects at the cellular level result from interaction of VEGFR-2 receptor with its ligand VEGF-A [17, 18]. VEGF-A is produced by T lymphocytes, macrophages, and platelets.…”

“…One of the important physiological functions of VEGF-A is its “participation” in the regulation of angiogenesis and proliferation of lymphatic vessels. At the same time an increasingly important role is attributed to VEGF-A in terms of its function as the increasing vascular permeability factor, as well as an important element in the process of vascular endothelial growth [18, 19]. Various studies concerning the processes of angiogenesis and factors involved in it have become the key to the origins of disease entities evoked by different reasons including, for instance, hypoxia and ischemia of the brain [4, 17, 20].…”