Implications of vascular endothelial growth factor for postischemic neurovascular remodeling

Hermann, Dirk Matthias; Zechariah, Anil

doi:10.1038/jcbfm.2009.100

Cited by 162Angiogenesis and VEGF in CancerNeurological Disease Mechanisms and TreatmentsBarrier Structure and Function Studies

Implications of vascular endothelial growth factor for postischemic neurovascular remodeling

Hermann, Dirk Matthias, Zechariah, Anil·2009·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/jcbfm.2009.100

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Abstract

Neurovascular remodeling has been recently recognized as a promising target for neurologic therapies. Hopes have emerged that, by stimulating vessel growth, it may be possible to stabilize brain perfusion, and at the same time promote neuronal survival, brain plasticity, and neurologic recovery. In this review, we outline the role of vascular endothelial growth factor (VEGF) in the ischemic brain, analyzing how this growth factor contributes to brain remodeling. Studies with therapeutic VEGF administration resulted in quite variable results depending on the route and time point of delivery. Local VEGF administration consistently enhanced neurologic recovery, whereas acute intravenous delivery exacerbated brain infarcts due to enhanced brain edema. Future studies should answer the following questions: (1) whether increased vessel density translates into improvements in blood flow in the hemodynamically compromised brain; (2) how VEGF influences brain plasticity and contributes to motor and nonmotor recovery; (3) what are the actions of VEGF not only in young animals with preserved vasculature, on which previous studies have been conducted, but also in aged animals and in animals with preexisting atherosclerosis; and (4) whether the effects of VEGF can be mimicked by pharmacological compounds or by cell-based therapies. Only on the basis of such information can more definite conclusions be made with regard to whether the translation of therapeutic angiogenesis into clinics is promising.

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Brain capillaries sprout and glial cells are activated to create a favourable cerebral environment for neuronal growth and plasticity.
“Additionally, brain capillaries sprout, and glial cells are activated to create a favourable cerebral environment for neuronal growth and plasticity.3,4”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [4]
After stroke, angiogenic factors are expressed by neurons and astrocytes, which induce microvascular growth.
“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 [4]
VEGF acting through VEGFR2 induces endothelial proliferation and concurrently upregulates delta-like ligand 4, which signals to microvascular cells in the capillary stalk to downregulate VEGFR2 via Notch 1, preventing uncontrolled capillary sprouting.
“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 [4]
Enhanced perfusion directly provides for the metabolic needs of the tissue.
“This enhanced perfusion directly provides for the metabolic needs of the tissue.4”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [4]

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Περιεγχειρητική διακύμανση του αυξητικού παράγοντα αγγειακού ενδοθηλίου (vascular endothelial growth factor/VEGF) σε ασθενείς με καρκίνο παχέος εντέρου και ασθενείς με καρκίνο μαστού
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Authors: Hermann, D. M., & Zechariah, A.
Affiliations: Essen University Hospital (DE)
Corresponding author: Hermann, Dirk Matthias
ORCID: Hermann, Dirk Matthias
Zechariah, Anil
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2009-08-05
Volume: 29
Issue: 10
Pages: 1620-1643
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1038/jcbfm.2009.100
OpenAlex: W1970165453
Cited by: 162
References: 165
Citations by year: 2026: 4 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 12 · 2015: 12 · 2014: 15 · 2013: 16 · 2012: 14
FWCI: 0.79
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: vascular endothelial growth factor, neurovascular remodeling, ischemic brain, therapeutic angiogenesis, postischemic recovery, neuroplasticity, cerebral edema, atherosclerosis, aging, cell therapy, neurological recovery
MeSH terms: Animals, Brain Ischemia, Humans, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A

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Implications of vascular endothelial growth factor for postischemic neurovascular remodeling

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