VEGF Promotes Angiogenesis and Functional Recovery in Stroke Rats

Abstract

We evaluated the effects of intranasal vascular endothelial growth factor VEGF on neurological function and angiogenesis in ischemic boundary following cerebral ischemia. Sprague-Dawley rats were randomized into sham operation group (n = 9), VEGF group (n = 18), and control group (n = 18). The VEGF and control rats were intranasally administered (IN) with VEGF or saline, starting three days after middle cerebral artery occlusion (MCAO) and daily. Neurological scores were obtained at 1, 7, and 14 days after MCAO. Rats were sacrificed at 14 days, the von Willebrand factor (vWF) immunoreactive, BrdU(+)/vWF(+) cells, and microvessels were evaluated respectively. Compared to the control rats, intranasal administration of VEGF improved behavioral recovery, and increased the number of vWF(+), BrdU(+)/vWF(+) cells, and FITC-dextran perfused microvessels in ischemic boundary (p < .01). Our data suggest that intranasal administration of VEGF may induce angiogenesis in ischemic boundary and improve behavioral recovery following cerebral ischemia in rats, which may provide a powerful strategy for stroke.

Long-term cerebral cortex protection and behavioral stabilization by gonadal steroid hormones after transient focal hypoxia

“…Hypoxic conditions disrupt the BBB and cause a rapid loss of brain equilibrium [26]. VEGF is known to induce angiogenesis in the ischemic boundary and improves behavioral recovery after ischemia [27] but also leads to a leakage of the BBB through its effects on endothelial tight junctions [28]. The duality of VEGF on stroke-related pathophysiological parameters in the brain (disruption of BBB and likewise neuroprotection by the formation of new blood vessels) is another example for the multiplicity of actions of protective agents.…”

Association Between VEGF Polymorphisms and Homocysteine Levels in Patients With Ischemic Stroke and Silent Brain Infarction

“…Intranasal administration of VEGF may induce angiogenesis in the ischemic boundary and improve behavioral recovery after cerebral ischemia in rats. 49 Astrocytes, which morphologically resemble injury-induced VEGF-positive cells, also react to injury by increasing VEGF expression, indicating that VEGF might participate in the central nervous system response to injury. 50 Therefore, VEGF may improve the histological and functional outcomes of stroke through multiple mechanisms.…”

Proof of Concept: Endogenous Antiangiogenic Factors Predict the Occurrence of Symptomatic Vasospasm Post Subarachnoid Hemorrhage

“…It's been hypothesized that VEGF is deleterious for the brain as it induces vascular remodeling and persistent wall stiffening [3]. Alternatively, it has been proposed that VEGF is neuroprotective against cerebrovascular injury as it induces vascular sprouting and angiogenesis, increases brain plasticity, and enhances vascular relaxation probably by boosting endothelial NO levels [22][23][24]. TGF-b in the CSF originates from the extravasated blood and from the choroids plexus.…”