The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
VEGF overexpression induces post-ischaemic neuroprotection, but facilitates haemodynamic steal phenomena
Open accessAbstract
Therapeutic angiogenesis with vascular endothelial growth factor (VEGF) is a clinically promising strategy in ischaemic disease. The pathophysiological consequences of enhanced vessel formation, however, are poorly understood. We established mice overexpressing human VEGF165 under a neuron-specific promoter, which exhibited an increased density of brain vessels under physiological conditions and enhanced angiogenesis after brain ischaemia. Following transient intraluminal middle cerebral artery (MCA) occlusions, VEGF overexpression significantly alleviated neurological deficits and infarct volume, and reduced disseminated neuronal injury and caspase-3 activity, confirming earlier observations that VEGF has neuroprotective properties. Brain swelling was not influenced in VEGF-overexpressing animals, while sodium fluorescein extravasation was moderately increased, suggesting that VEGF induces a mild blood-brain barrier leakage. To elucidate whether enhanced angiogenesis improves regional cerebral blood flow in the ischaemic brain, [14C]iodoantipyrine autoradiography was performed. Autoradiographies revealed that VEGF induces haemodynamic steal phenomena with reduced blood flow in ischaemic areas and increased flow values only outside the MCA territory. Our data demonstrate that VEGF protects neurons from ischaemic cell death by a direct action rather than by promoting angiogenesis, and suggest that strategies aiming at increasing vascular density in the whole brain, e.g. by VEGF overexpression, may worsen rather than improve cerebral haemodynamics after stroke.
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“Acting through VEGF receptor 2 (VEGFR2), which is localised at high concentrations at the tip of newly formed capillaries, VEGF induces endothelial proliferation,4,47–49 and concur rently upregulates the transmembrane ligand delta-like ligand 4, which signals to microvascular cells in the capillary stalk, to downregulate VEGFR2 via interaction with its receptor Notch 1, thus pre venting uncontroll”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [49]
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“After stroke, angiogenic factors are expressed by neurons and astrocytes, which induce microvascular growth.4,47–50”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [49]
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Metadata
- Authors
- Wang, Y.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Wang, Y.
- ORCID
- Wang, Y.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-11-17
- Volume
- 128
- Issue
- 1
- Pages
- 52-63
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2166050160
- Cited by
- 221
- References
- 55
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 14 · 2015: 5 · 2014: 16 · 2013: 20 · 2012: 12
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (67256, 100790, 3200B0)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- VEGF overexpression, therapeutic angiogenesis, cerebral ischemia, neuroprotection, regional cerebral blood flow, middle cerebral artery occlusion, blood-brain barrier disruption, neuronal injury, caspase-3, stroke, VEGF165, cerebral angiogenesis
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Capillaries, Capillary Permeability, Brain Ischemia, Cerebrovascular Circulation, Hemodynamics, Humans, Mice, Transgenic, Necrosis, Neovascularization, Pathologic, Neurons, Stroke, Middle Cerebral Artery, Vascular Endothelial Growth Factor A, Mice
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