Cited by 1,296Barrier Structure and Function StudiesAngiogenesis and VEGF in CancerAcute Ischemic Stroke Management

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VEGF enhances angiogenesis and promotes blood–brain barrier leakage in the ischemic brain

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Zhang, Zheng Gang, Zhang, Li, Jiang, Quan, Zhang, Ruilan, Davies, Kenneth, Powers, Cecylia, Bruggen, Nicholas van, Chopp, Michael·2000·Journal of Clinical Investigation

DOI 10.1172/jci9369PMC PMC517814

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Abstract

VEGF is a secreted mitogen associated with angiogenesis and is also a potent vascular permeability factor. The biological role of VEGF in the ischemic brain remains unknown. This study was undertaken to investigate whether VEGF enhances cerebral microvascular perfusion and increases blood-brain barrier (BBB) leakage in the ischemic brain. Using magnetic resonance imaging (MRI), three-dimensional laser-scanning confocal microscope, and functional neurological tests, we measured the effects of administrating recombinant human VEGF(165) (rhVEGF(165)) on angiogenesis, functional neurological outcome, and BBB leakage in a rat model of focal cerebral embolic ischemia. Late (48 hours) administration of rhVEGF(165) to the ischemic rats enhanced angiogenesis in the ischemic penumbra and significantly improved neurological recovery. However, early postischemic (1 hour) administration of rhVEGF(165) to ischemic rats significantly increased BBB leakage, hemorrhagic transformation, and ischemic lesions. Administration of rhVEGF(165) to ischemic rats did not change BBB leakage and cerebral plasma perfusion in the contralateral hemisphere. Our results indicate that VEGF can markedly enhance angiogenesis in the ischemic brain and reduce neurological deficits during stroke recovery and that inhibition of VEGF at the acute stage of stroke may reduce the BBB permeability and the risk of hemorrhagic transformation after focal cerebral ischemia.

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BackgroundInfluential
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“41, 42 In one prior study which measured VEGF in the plasma and CSF of aSAH patients, the cytokine was found to be elevated in CSF from aSAH patients compared to control CSF and in aSAH patient CSF compared to plasma, but no differences were found between aSAH patient and control plasma.”
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Background
Longshengzhi Capsules Improve Ischemic Stroke Outcomes and Reperfusion Injury via the Promotion of Anti‐Inflammatory and Neuroprotective Effects in MCAO/R Rats
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“+us far, the most compelling argument has been that VEGF increases BBB permeability in the early phase of ischemic stroke and subsequently facilitates neurovascular remodeling [63].”
BackgroundSelf-citation
Missense Variants in Hypoxia-Induced VEGFA/VEGFR2 Signaling Predict the Outcome of Large Artery Atherosclerotic Stroke
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Self-citation
Poly(Ester Amide) Microspheres are Efficient Vehicles for Long-Term Intracerebral Growth Factor Delivery and Improve Functional Recovery after Stroke
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Exogenous endothelial progenitor cells reached the deficient region of acute cerebral ischemia rats to improve functional recovery via Bcl-2
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“Compared with other therapeutic strategies such as the use vascular endothelial growth factor (VEGF) (31,32) and granulocyte-colony stimulating factor (G-CSF) (33-35), EPC transplantation holds more advantages.”
Self-citation
Intra-arterial Transplantation of Human Umbilical Cord Blood Mononuclear Cells in Sub-acute Ischemic Stroke Increases VEGF Expression in Rats
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Protective Effects of Natrii Sulfas on Cerebral Focal Ischemia Induced by MCAO in Rats
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Background
Minimally Invasive Syringe‐Injectable Hydrogel with Angiogenic Factors for Ischemic Stroke Treatment
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BackgroundInfluential
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Aldehyde Dehydrogenase 2 (ALDH2) Glu504Lys Polymorphism Affects Collateral Circulation and Short-Term Prognosis of Acute Cerebral Infarction Patients
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Background
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Background
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BackgroundMethod
Stroke and the Blood‐Brain Interface
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Brain metastasis localized to the same area of infarction: illustrative case
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“VEGF’s main job is to encourage the growth of new blood vessels (angiogenesis) in response to damaged or ischemic (not enough blood flow) tissue.(23) However, this elevated VEGF level may unintentionally help metastatic FIG.”
Background

Authors: Zhang, Z. G., Zhang, L., Jiang, Q., Zhang, R., Davies, K., Powers, C., Bruggen, N. V., & Chopp, M.
Affiliations: Henry Ford Health (US)
Henry Ford Hospital (US)
Genentech (US)
Oakland University (US)
Corresponding author: Chopp, Michael
ORCID: Zhang, Zheng Gang
Zhang, Li
Jiang, Quan
Chopp, Michael
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2000-10-01
Volume: 106
Issue: 7
Pages: 829-838
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci9369
PMC: PMC517814
OpenAlex: W2084498863
Cited by: 1,296
References: 75
Citations by year: 2026: 32 · 2025: 49 · 2024: 53 · 2023: 52 · 2022: 64 · 2021: 73 · 2020: 58 · 2019: 42 · 2018: 59 · 2017: 59 · 2016: 61 · 2015: 49 · 2014: 70 · 2013: 70 · 2012: 64
FWCI: 13.44
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ns033627-08)
National Institute of Neurological Disorders and Stroke (P01NS23393, R01NS-33627, P01NS023393)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Keywords: vascular endothelial growth factor, angiogenesis, blood-brain barrier disruption, cerebral ischemia, hemorrhagic transformation, ischemic penumbra, neurological recovery, VEGF inhibition, stroke
MeSH terms: Animals, Blood-Brain Barrier, Brain Ischemia, Image Processing, Computer-Assisted, Lymphokines, Magnetic Resonance Imaging, Male, Microcirculation, Neovascularization, Pathologic, Regional Blood Flow, Endothelial Growth Factors, Treatment Outcome, Rats, Wistar, Stroke, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Rats

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VEGF enhances angiogenesis and promotes blood–brain barrier leakage in the ischemic brain

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