scholarly journals VEGF Protects Brain against Focal Ischemia without Increasing Blood–Brain Permeability When Administered Intracerebroventricularly

2005 ◽  
Vol 25 (9) ◽  
pp. 1111-1118 ◽  
Author(s):  
Dilaver Kaya ◽  
Yasemin Gürsoy-Özdemir ◽  
Muge Yemisci ◽  
Neşe Tuncer ◽  
Sevinç Aktan ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Time Window ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Hemorrhagic Transformation ◽  
Vascular Endothelial ◽  
Blood Brain ◽  
Endothelial Growth Factor

Delayed administration of vascular endothelial growth factor (VEGF) promotes functional recovery after focal cerebral ischemia. However, early intravenous injection of VEGF increases blood–brain barrier (BBB) leakage, hemorrhagic transformation and infarct volume whereas its application to cortical surface is neuroprotective. We have investigated whether or not early intracerebroventricular administration of VEGF could replicate the neuroprotective effect observed with topical application and the mechanism of action of this protection. Mice were subjected to 90 mins middle cerebral artery (MCA) occlusion and 24 h of reperfusion. Vascular endothelial growth factor (8 ng, intracerebroventricular) was administered 1 or 3 h after reperfusion. Compared with the vehicle-treated (intracerebroventricular) group, VEGF decreased the infarct volume along with BBB leakage in both treatment groups. Neurologic disability scores improved in parallel to the changes in infarct volume. Independently of the decrease in infarct size, VEGF also reduced the number of TUNEL-positive apoptotic neurons. Phospo-Akt levels were significantly higher in ischemic hemispheres of the VEGF-treated mice. Contrary to intracerebroventricular route, intravenous administration of VEGF (15 μg/kg) enhanced the infarct volume as previously reported for the rat. In conclusion, single intracerebroventricular injection of VEGF protects brain against ischemia without adversely affecting BBB permeability, and has a relatively long therapeutic time window. This early neuroprotective action, observed well before recovery-promoting actions such as angiogenesis, possibly involves activation of the PI-3-Akt pathway.

scholarly journals Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2844-2853 ◽  
Author(s):  
Su Jing Chan ◽  
Elga Esposito ◽  
Kazuhide Hayakawa ◽  
Emiri Mandaville ◽  
Raymond A.A. Smith ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Blood Brain Barrier ◽  
Neural Progenitor Cells ◽  
Brain Barrier ◽  
Vascular Endothelial ◽  
Brain Endothelial Cell ◽  
Blood Brain ◽  
Endothelial Growth Factor

Background and Purpose: Although VEGF 165 (vascular endothelial growth factor-165) is able to enhance both angiogenesis and neurogenesis, it also increases vascular permeability through the blood-brain barrier. Heparan sulfate (HS) sugars play important roles in regulating VEGF bioactivity in the pericellular compartment. Here we asked whether an affinity-purified VEGF 165 -binding HS (HS7) could augment endogenous VEGF activity during stroke recovery without affecting blood-brain barrier function. Methods: Both rat brain endothelial cell line 4 and primary rat neural progenitor cells were used to evaluate the potential angiogenic and neurogenic effects of HS7 in vitro. For in vivo experiments, male Sprague-Dawley rats were subjected to 100 minutes of transient focal cerebral ischemia, then treated after 4 days with either PBS or HS7. One week later, infarct volume, behavioral sequelae, immunohistochemical markers of angiogenesis and neural stem cell proliferation were assessed. Results: HS7 significantly enhanced VEGF 165 -mediated angiogenesis in rat brain endothelial cell line 4 brain endothelial cells, and increased the proliferation and differentiation of primary neural progenitor cells, both via the VEGFR2 (vascular endothelial growth factor receptor 2) pathway. Intracerebroventricular injection of HS7 improved neurological outcome in ischemic rats without changing infarct volumes. Immunostaining of the compromised cerebrum demonstrated increases in collagen IV/Ki67 and nestin/Ki67 after HS7 exposure, consistent with its ability to promote angiogenesis and neurogenesis, without compromising blood-brain barrier integrity. Conclusions: A VEGF-activating glycosaminoglycan sugar, by itself, is able to enhance endogenous VEGF 165 activity during the post-ischemic recovery phase of stroke.

scholarly journals Vascular Endothelial Growth Factor Increases during Blood-Brain Barrier-Enhanced Permeability Caused byPhoneutria nigriventerSpider Venom

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Monique C. P. Mendonça ◽  
Edilene S. Soares ◽  
Leila M. Stávale ◽  
Evanguedes Kalapothakis ◽  
Maria Alice Cruz-Höfling
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Ion Channels ◽  
Growth Factor ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Blood Brain ◽  
Calbindin D28k ◽  
Endothelial Growth Factor

Phoneutria nigriventerspider accidental envenomation provokes neurotoxic manifestations, which when critical, results in epileptic-like episodes. In rats,P. nigriventervenom (PNV) causes blood-brain barrier breakdown (BBBb). The PNV-induced excitotoxicity results from disturbances on Na+, K+and Ca2+channels and glutamate handling. The vascular endothelial growth factor (VEGF), beyond its angiogenic effect, also, interferes on synaptic physiology by affecting the same ion channels and protects neurons from excitotoxicity. However, it is unknown whether VEGF expression is altered following PNV envenomation. We found that adult and neonates rats injected with PNV showed immediate neurotoxic manifestations which paralleled with endothelial occludin,β-catenin, and laminin downregulation indicative of BBBb. In neonate rats, VEGF, VEGF mRNA, and Flt-1 receptors, glutamate decarboxylase, and calbindin-D28k increased in Purkinje neurons, while, in adult rats, the BBBb paralleled with VEGF mRNA, Flk-1, and calbindin-D28k increases and Flt-1 decreases. Statistically, the variable age had a role in such differences, which might be due to age-related unequal maturation of blood-brain barrier (BBB) and thus differential cross-signaling among components of the glial neurovascular unit. The concurrent increases in the VEGF/Flt-1/Flk-1 system in the cerebellar neuron cells and the BBBb following PNV exposure might imply a cytokine modulation of neuronal excitability consequent to homeostatic perturbations induced by ion channels-acting PNV neuropeptides. Whether such modulation represents neuroprotection needs further investigation.

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