The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
VEGF enhances angiogenesis and promotes blood–brain barrier leakage in the ischemic brain
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As a pleiotropic growth factor, VEGF is responsible for multiple important physiological functions, particularly BBB permeability [44, 50, 51].”
From Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain (2022) · cites this paper as [50]
Experimental — accuracy not yet measuredIn the citing paper
“Similar findings about the importance of timing for administration of a neurorestorative therapy for stroke have been reported for VEGF94 and modulators of matrix metallo proteinases.95”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [94]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Le Bihan, D., Breton, E., Lallemand, D., Grenier, P., Cabanis, E., & Laval-Jeantet, M. (1986) · Radiology · doi:10.1148/radiology.161.2.3763909 · Cited by 3,912
Dvorak, H. F., Brown, L. F., Detmar, M. J., & Dvořàk, A. M. (1995) · Europe PMC (PubMed Central) · Cited by 3,100
FINE STRUCTURAL LOCALIZATION OF A BLOOD-BRAIN BARRIER TO EXOGENOUS PEROXIDASE
Reese, T. S., & Karnovsky, M. J. (1967) · The Journal of Cell Biology · doi:10.1083/jcb.34.1.207 · Cited by 2,629
Magnetic resonance imaging of perfusion using spin inversion of arterial water.
Williams, D. S., Detre, J. A., Leigh, J. S., & Koretsky, A. P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.1.212 · Cited by 1,553
Leakage-Resistant Blood Vessels in Mice Transgenically Overexpressing Angiopoietin-1
Thurston, G., Suri, C., Smith, K., McClain, J., Sato, T. T., Yancopoulos, G. D., & McDonald, D. M. (1999) · Science · doi:10.1126/science.286.5449.2511 · Cited by 1,350
Angiopoietin-1 protects the adult vasculature against plasma leakage
Thurston, G., Rudge, J. S., Ioffe, E., Zhou, H., Ross, L. H., Croll, S. D., Glazer, N. L., Holash, J. A., McDonald, D. M., & Yancopoulos, G. D. (2000) · Nature Medicine · doi:10.1038/74725 · Cited by 1,314
Peptide Growth Factors and Their Receptors
Arai, K., Battey, J. F., Sporn, M. B., & Roberts, A. B. (1991) · Medical Entomology and Zoology · Cited by 1,225
Breier, G., Albrecht, U., Sterrer, S., & Risau, W. (1992) · Development · doi:10.1242/dev.114.2.521 · Cited by 1,087
Takeshita, S., Zheng, L., Brogi, E., Kearney, M., Pu, L. L. Q., Bunting, S., Ferrara, N., Symes, J. F., & Isner, J. M. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117018 · Cited by 1,034
A functional MRI study of subjects recovered from hemiparetic stroke
Cramer, S. C., Nelles, G., Benson, R. R., Kaplan, J. D., Parker, R. A., Kwong, K. K., Kennedy, D. N., Finklestein, S. P., & Rosen, B. R. (1997) · Stroke · doi:10.1161/01.str.28.12.2518 · Cited by 1,019
Flagged first, then by citations
Research works printed but not linked: 8
- Carmeliet, 1997, Am J Physiol, 273, H2091
- Aiello, 1997, Invest Ophthalmol Vis Sci, 38, 1647
- Dvorak, 1995, Am J Pathol, 146, 1029
- Hatashita, 1990, Adv Neurol, 52, 327
- Lyden, 1993, Cerebrovasc Brain Metab Rev, 5, 1
- Dellian, 1996, Am J Pathol, 149, 59
- Cancilla, 1979, Lab Invest, 40, 74
- Criscuolo, 1990, Adv Neurol, 52, 469
Cited by
Sorted by citations
Items 501–600 of 1,000
Diabetes AugmentsIn VivoMicrovascular Blood Flow Dynamics after Stroke
Tennant, K. A., & Brown, C. E. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3513-13.2013 · Cited by 45
“In agreement with histological and acute two-photon imaging studies that showed increased vessel density in the ischemic border zone (Zhang et al., 2000; Brown et al., 2007; Zhang and Chopp, 2009; Gertz et al., 2012), we did find a transient increase in vascular density in peri-infarct cortex, but this was likely rela…”
BackgroundLeBlanc, N. J., Guruswamy, R., & ElAli, A. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0478-6 · Cited by 46
“This relationship is governed by the neurovascular unit (NVU), which comprises tightly sealed endothelial cells, forming the blood-brain barrier (BBB), that interact with extracellular matrix proteins, pericytes, astrocyte end-feet, microglia, and neurons [2] [3].”
InfluentialWang, H., Zhang, X., Tomiyoshi, G., Nakamura, R., Shinmen, N., Kuroda, H., Kimura, R., Mine, S., Kamitsukasa, I., Wada, T., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.23789 · Cited by 46
“Cerebral infarction (CI), namely ischemic stroke, is the most common cerebrovascular disorder worldwide and is a major cause of fatality and disability [1-3].”
BackgroundNovel pyrazolo[1,5-a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade
Mukaiyama, H., Nishimura, T., Kobayashi, S., Komatsu, Y., Kikuchi, S., Ozawa, T., Kamada, N., & Ohnota, H. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.10.068 · Cited by 46
Santra, M., Santra, S., Zhang, J., & Chopp, M. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05134.x · Cited by 46
Self-citationBix, G. J., Gowing, E. K., & Clarkson, A. N. (2013) · Translational Stroke Research · doi:10.1007/s12975-013-0266-1 · Cited by 46
“An example of this is vascular endothelial growth factor (VEGF), which may further destabilize the blood–brain barrier, promote brain edema, and enhance hemorrhagic transformation and brain infarct size when administered acutely [32] but is neuroprotective and enhances angiogenesis and neurogenesis when given chronica…”
Zhang, L., Li, Y., Romanko, M. J., Kramer, B. C., Gosiewska, A., Chopp, M., & Hong, K. (2012) · Brain Research · doi:10.1016/j.brainres.2012.10.017 · Cited by 45
Self-citationSong, J., Kang, S. M., Lee, W. T., Park, K. A., Lee, K. M., & Lee, J. E. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/639531 · Cited by 45
“During ischemia, VEGF interacts with receptors for VEGF on the ischemic vessels and contributes to disruption of the BBB [43, 44].”
BackgroundQi, H., Su, H., Marchuk, D. A., Rola, R., Wang, Y., Liu, W., Young, W. L., & Yang, G. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00083.2008 · Cited by 45
“the normal diameter of a capillary is between 3 and 8 m (49).”
Refueling the Ischemic CNS: Guidance Molecules for Vascular Repair
Rust, R., Grönnert, L., Weber, R., Mulders, G., & Schwab, M. E. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.05.006 · Cited by 44
Jiang, L., Mu, H., Xu, F., Xie, D., Su, W., Xu, J., Sun, Z., Liu, S., Luo, J., Shi, Y., et al. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20902542 · Cited by 46
Potential Therapies for Cerebral Edema After Ischemic Stroke: A Mini Review
Yao, Y., Zhang, Y., Liao, X., Yang, R., Lei, Y., & Luo, J. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.618819 · Cited by 44
Lennmyr, F., Ericsson, A. B., Gerwins, P., Ahlström, H. K., & Terént, A. (2003) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.2003.00129.x · Cited by 45
“Exogenous VEGF increases vascular leakage and may aggravate ischemic injury if administered in the acute phase (14), and it has been proposed that endogenous VEGF may have similar effects by activating Srcdependent pathways (15).”
BackgroundBogaert, E., Damme, P. V., Bosch, L. V. D., & Robberecht, W. (2006) · Muscle & Nerve · doi:10.1002/mus.20609 · Cited by 45
VEGF: necessary to prevent motoneuron degeneration, sufficient to treat ALS?
Lambrechts, D., Storkebaum, E., & Carmeliet, P. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.04.004 · Cited by 46
Biomarkers Assessing Endothelial Dysfunction in Alzheimer’s Disease
Custodia, A., Aramburu-Núñez, M., Rodríguez‐Arrizabalaga, M., Peleteiro, J. M. P., Vázquez‐Vázquez, L., Camino-Castiñeiras, J., Aldrey, J. M., Castillo, J., Ouro, A., Sobrino, T., et al. (2023) · Cells · doi:10.3390/cells12060962 · Cited by 47
“However, under ischemic conditions, VEGF also has harmful effects on the central nervous system by promoting BBB leakage in the brain [116] (Figure 2).”
BackgroundmiR-376b-5p regulates angiogenesis in cerebral ischemia
Li, L., Huang, Q. B., Zhang, N., WANG, G.-B., & LIU, Y.-H. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2172 · Cited by 44
“Zhang et al (25) revealed that following focal cerebral ischemia, the expression of VEGFA and VEGFR were significantly increased around the infarcted area.”
Yuan, Y., Fang, S., Qian, X., Liu, L., Xu, L.-H., Shi, W., Zhang, L., Lu, Y., Zhang, W., & Wei, E.-Q. (2009) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08321fp · Cited by 44
Self-citationCastillo-Meléndez, M., Yawno, T., Sutherland, A. E., Jenkin, G., Wallace, E. M., & Miller, S. (2017) · Developmental Neuroscience · doi:10.1159/000471797 · Cited by 46
Cheng, P., Ma, L., Shaligram, S. S., Walker, E. J., Yang, S., Tang, C., Zhu, W., Zhan, L., Li, Q., Zhu, X., et al. (2019) · Journal of neurosurgery · doi:10.3171/2019.1.jns183112 · Cited by 44
Non-coding RNAs: the extensive and interactive regulators of the blood-brain barrier permeability
Yang, R., Xu, B., Yang, B., Fu, J., Chen, H., & Wang, X. (2021) · RNA Biology · doi:10.1080/15476286.2021.1950465 · Cited by 45
HIF-1 alpha inhibition ameliorates neonatal brain damage after hypoxic-ischemic injury
Chen, W., Jadhav, V. R., Tang, J., & Zhang, J. H. (2008) · Acta neurochirurgica. Supplementum · doi:10.1007/978-3-211-85578-2_77 · Cited by 44
“Some studies have shown that HIF-1α induction by hypoxic preconditioning or HIF-1α inducer such as deferoxamine is required for neuronal protection [2, 15 ].”
BackgroundEffects of vascular endothelial growth factor on isolated fetal alveolar type II cells
Raoul, W., Chailley‐Heu, B., Barlier‐Mur, A., Delacourt, C., Maître, B., & Bourbon, J. R. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00157.2003 · Cited by 44
“Nevertheless, that human recombinant VEGF would have been more efficient in homologous system [human lung explants (5)] but would not have stimulated rat type II cell proliferation because of interspecies differences in responsiveness is unlikely, because 1) it has already been shown previously to exert a variety of b…”
BackgroundHwang, S., Choi, J., & Kim, M. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00357 · Cited by 43
“The VEGF, a key angiogenic and permeability factor (24, 25), increases cerebral microvascular perfusion and induces neurological recovery when administered 48 h after ischemic stroke (38).”
BackgroundThe Molecular Mechanisms of Ferroptosis and Its Role in Blood-Brain Barrier Dysfunction
Chen, X., Pang, X., Yeo, A. J., Xie, S., Xiang, M., Shi, B., Yu, G., & Li, C. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.889765 · Cited by 46
“Iron chelator treatment attenuated iron accumulation and suppressed neuroinflammation, which further decreased the BBB impairment and the damage of dopaminergic neurons (OlmedoDiaz et al., 2017; Tai et al., 2020; Han et al., 2021; Riederer et al., 2021; Zhao et al., 2021).”
BackgroundNeutrophil dynamics and inflammaging in acute ischemic stroke: A transcriptomic review
Bui, T. A., Jickling, G. C., & Winship, I. R. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1041333 · Cited by 46
“Additionally, upon VEGF administration, both rat and mouse models have been shown to have higher new vessel density and better functional recovery (Zhang et al., 2000; Hayashi et al., 2003).”
BackgroundDetrimental Roles of Hypoxia-Inducible Factor-1α in Severe Hypoxic Brain Diseases
Choi, Y. K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084465 · Cited by 45
“Inflammatory factors induce BBB leakage by changing the structures of tight junction proteins [141,142].”
BackgroundMiners, J. S., Moulding, H., de Silva, R., & Love, S. (2014) · Brain Pathology · doi:10.1111/bpa.12130 · Cited by 45
“mechanism which underlie reduced CBF in DLB and found that (i) the levels of ET-1 and ACE, two potent vasoconstrictors that are upregulated in the cerebral cortex in AD, were unchanged in DLB (ii); VEGF, a potent pro-angiogenic factor (41, 64), is reduced in DLB (iii); FVIIIRA level, a good surrogate marker of capilli…”
BackgroundActivation of PI3 Kinase/Akt Signaling in Chronic Subdural Hematoma Outer Membranes
Funai, M., Osuka, K., Usuda, N., Atsuzawa, K., Inukai, T., Yasuda, M., Watanabe, Y., & Takayasu, M. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1498 · Cited by 43
“, 1998), especially in the ischemic brain, improving neurological recovery (Zhang et al., 2000).”
Zhao, Y., Li, Z., Wang, R., Wei, J., Li, G., & Zhao, H. (2009) · Neurological Research · doi:10.1179/016164109x12445616596562 · Cited by 43
Wu, C., Hu, Q., Chen, J., Yan, F., Li, J., Wang, L., Mo, H., Gu, C., Zhang, P., & Chen, G. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.06.107 · Cited by 44
“The up-regulation of VEGF found in brain tissues after SAH may exacerbate BBB disruption [38,39]; in strong support, several studies showed that inhibition of VEGF significantly attenuated brain edema induced by cerebral ischemia/reperfusion [40] and SAH [4].”
ResultYan, T., Venkat, P., Chopp, M., Zacharek, A., Ning, R., Roberts, C. J., Zhang, Y., Lü, M., & Chen, J. (2016) · Stroke · doi:10.1161/strokeaha.116.014686 · Cited by 43
“the ischemic penumbra and significantly improves neurological functional recovery.(13) Because diabetic rats suffer from vascular damage,(18) which is aggravated after an ischemic insult,(12)”
BackgroundMethodSelf-citationZong, X., Wu, S., Li, F., Lv, L., Han, D. K., Zhao, N., Yan, X., Hu, S., & Xu, T. J. (2017) · Brain Research · doi:10.1016/j.brainres.2017.08.006 · Cited by 43
A Mesenchymal stem cell line (B10) increases angiogenesis in a rat MCAO model
Sheikh, A. M., Yano, S., Mitaki, S., Haque, M. A., Yamaguchi, S., & Nagai, A. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.10.001 · Cited by 43
Yang, H., Luo, Y., Hu, H., Yang, S., Li, Y., Jin, H., Chen, S., He, Q., Hong, C., Wu, J., et al. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202100028 · Cited by 43
Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization
Dhaou, C. B., Mandi, K., Frye, M., Acheampong, A., Radi, A., Becker, B. D., Antoine, M., Baeyens, N., Wittamer, V., & Parmentier, M. (2021) · Angiogenesis · doi:10.1007/s10456-021-09818-1 · Cited by 43
Gene Transfer of Hepatocyte Growth Factor to Subarachnoid Space in Cerebral Hypoperfusion Model
Yoshimura, S., Morishita, R., Hayashi, K., Kokuzawa, J., Aoki, M., Matsumoto, K., Nakamura, T., Ogihara, T., Sakai, N., & Kaneda, Y. (2002) · Hypertension · doi:10.1161/01.hyp.0000017553.67732.e1 · Cited by 43
Kapoor, A., Gaubert, A., Marshall, A. J., Meier, I. B., Yew, B., Ho, J. K., Blanken, A. E., Dutt, S., Sible, I. J., Li, Y., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.711784 · Cited by 42
Extracellular vesicle therapy in neurological disorders
Putthanbut, N., Lee, J.-Y., & Borlongan, C. V. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01075-w · Cited by 44
“Overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) can potentially lead to BBB leakage and brain edema [206, 207].”
BackgroundKlintsova, A. Y., Hamilton, G. F., & Boschen, K. E. (2012) · Brain Sciences · doi:10.3390/brainsci3010001 · Cited by 51
“For example, vascular endothelial growth factor (VEGF) is critical for angiogenesis during development and adulthood, and can affect the permeability of the blood-brain barrier [168].”
BackgroundMagnetic Resonance Imaging in Experimental Stroke and Comparison With Histology
Milidonis, X., Marshall, I., Macleod, M. R., & Sena, E. S. (2015) · Stroke · doi:10.1161/strokeaha.114.007560 · Cited by 43
Lee, J., Tae, H., Kim, I. H., Cho, J.-H., Lee, T.-K., Park, J. H., Ahn, J. H., Choi, S. Y., Bai, H. C., Shin, B.-N., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0219-2 · Cited by 41
“It was demonstrated that VEGF promoted vascular permeability in the brain by altering tight junction proteins under ischemic condition [58].”
BackgroundLigustilide provides neuroprotection by promoting angiogenesis after cerebral ischemia
Ren, C., Li, N., Chen, G., Zhang, W., Yang, Y., Li, S., Ji, X., & Ding, Y. (2020) · Neurological Research · doi:10.1080/01616412.2020.1782122 · Cited by 41
“Notably, intravenous VEGF increased microvessel density in the cortical ischemia penumbra after focal ischemia in rats [8].”
BackgroundBahadar, G. A., & Shah, Z. A. (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666210223145112 · Cited by 42
Davis, B., Tang, J., Zhang, L., Mu, D., Jiang, X., Biran, V., Vexler, Z. S., & Ferriero, D. M. (2010) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2010.06.010 · Cited by 42
“Conversely, delayed VEGF administration at 48 h after stroke enhanced angiogenesis and improved neurological outcome (Zhang et al., 2000).”
BackgroundSelf-citationKumai, Y., Ooboshi, H., Ibayashi, S., Ishikawa, E., Sugimori, H., Kamouchi, M., Kitazono, T., Egashira, K., & Iida, M. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600420 · Cited by 41
“…on either luminal or abluminal side by different administration routes may lead to differences in signaling pathways in angiogenesis, intravenous (Zhang et al, 2000), intra-arterial (Abumiya et al, 2005), or intraventricular (Sun et al, 2003) administration of VEGF promotes angiogenesis in…”
BackgroundYoung, P. P., Fantz, C. R., & Sands, M. S. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.03.007 · Cited by 41
Emerging therapeutic targets for cerebral edema
Jha, R. M., Raikwar, S. P., Mihaljević, S., Casabella, A. M., Catapano, J. S., Rani, A., Desai, S. M., Gerzanich, V., & Simard, J. M. (2021) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.2010045 · Cited by 41
“BBB integrity and endothelial cell survival; however, at high levels, it increases vascular permeability and cerebral edema [241,248,249].”
BackgroundAdvancing stroke therapy: A deep dive into early phase of ischemic stroke and recanalization
He, Q., Wang, Y., Fang, C., Feng, Z., Yin, M., Huang, J., Ma, Y., & Mo, Z. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14634 · Cited by 44
“85,86 Possible mechanisms include VEGF-mediated dissociation of tight junction proteins like occludin and ZO-1, increased activity of permeability factors like nitric oxide (NO) and MMPs, and enhanced vesicular transport across endothelial cells.”
BackgroundFan, S., Yan, X., Li, X., Tie, L., Pan, Y., & Li, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.06.019 · Cited by 41
Blood–Brain Barrier and Bilirubin: Clinical Aspects and Experimental Data
Brito, M. A., Palmela, I., Cardoso, F. L., Sá-Pereira, I., & Brites, D. M. T. O. (2014) · Archives of Medical Research · doi:10.1016/j.arcmed.2014.11.015 · Cited by 42
Smagula, S. F., Lotrich, F. E., Aizenstein, H. J., Diniz, B. S., Krystek, J. R., Wu, G. F., Mulsant, B. H., Butters, M. A., Reynolds, C. F., & Lenze, E. J. (2016) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4512 · Cited by 42
“VEGF increases the permeability of the blood brain barrier (Zhang et al., 2000) and might relate to grey matter volume by increasing the brain’s exposure to neurotoxic factors.”
BackgroundCheon, S. Y., Kim, E. J., Kim, J., & Koo, B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/2596043 · Cited by 41
“Previous studies have shown that administration of recombinant human VEGF165 exacerbates the breakdown of BBB integrity, which can be prevented by inhibiting VEGF at an early stage of ischemic stroke [46, 47].”
BackgroundSteroids in Stroke with Special Reference to Progesterone
Guennoun, R., Zhu, X., Fréchou, M., Gaignard, P., Slama, A., Lière, P., & Schumacher, M. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0627-0 · Cited by 41
LncRNA SNHG1 alleviates OGD induced injury in BMEC via miR-338/HIF-1α axis
Yang, X., & Zi, X. (2018) · Brain Research · doi:10.1016/j.brainres.2018.11.003 · Cited by 41
Chan, S. J., Esposito, E., Hayakawa, K., Mandaville, E., Smith, R. A. A., Guo, S., Niu, W., Wong, P. T. ‐., Cool, S. M., Lo, E. H., et al. (2020) · Stroke · doi:10.1161/strokeaha.119.025304 · Cited by 41
Pericytes for Therapeutic Approaches to Ischemic Stroke
Cao, L., Zhou, Y., Chen, M., Li, L., & Zhang, W. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.629297 · Cited by 41
Ex vivo gene therapy: transplantation of neurotrophic factor-secreting cells for cerebral ischemia
Yasuhara, T. (2006) · Frontiers in bioscience · doi:10.2741/1834 · Cited by 41
“Similarly, delayed administration of BDNF conjugated to the anti-transferrin receptor antibody at 2 hours after MCAO also displayed neurorescue effects on the ischemic rat brain (104, 105).”
BackgroundSakanaka, M., Zhu, P., Zhang, B., Wen, T., Cao, F., Ma, Y.-J., Samukawa, K., Mitsuda, N., Tanaka, J., Kuramoto, M., et al. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2006.0182 · Cited by 41
“Early treatment with VEGF (1 h post-ischemia) increased brain-blood barrier leakage, hemorrhagic transformation and ischemic lesions, while late treatment with VEGF (48 h post-ischemia) enhanced angiogenesis and significantly improved neurological recovery (Zhang et al., 2000).”
Extracellular proteolytic pathophysiology in the neurovascular unit after stroke
Lee, S.-R., Wang, X., Tsuji, K., & Lo, E. H. (2004) · Neurological Research · doi:10.1179/016164104x3806 · Cited by 43
MLC901 Favors Angiogenesis and Associated Recovery after Ischemic Stroke in Mice
Gandin, C., Widmann, C., Lazdunski, M., & Heurteaux, C. (2016) · Cerebrovascular Diseases · doi:10.1159/000444810 · Cited by 41
Serial cytokine alterations and abnormal neuroimaging in newborn infants with encephalopathy
O'Hare, F. M., Watson, R. W. G., O’Neill, A., Segurado, R., Sweetman, D., Downey, P., Mooney, E. E., Murphy, J., Donoghue, V. B., & Molloy, E. J. (2017) · Acta Paediatrica · doi:10.1111/apa.13745 · Cited by 40
“Topical application of VEGF reduces brain infarct size (18), and intravenous VEGF improves neurological outcome from ischaemia (19).”
BackgroundDynamic modulation of the blood–brain barrier in the healthy brain
Friedman, A., Prager, O., Serlin, Y., & Kaufer, D. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00976-5 · Cited by 48
Yang, Z., Cai, X., Xu, A., Xu, F., & Qin, L. (2015) · Cytotherapy · doi:10.1016/j.jcyt.2015.06.005 · Cited by 40
Palmela, I., Cardoso, F. L., Bernas, M. J., Correia, L., Vaz, A. R., Silva, R. F. M., Fernandes, A. M. A., Kim, K. S., Brites, D. M. T. O., & Brito, M. A. (2011) · Current Neurovascular Research · doi:10.2174/156720211795495358 · Cited by 40
“Other cytokines, such as the vascular endothelial growth factor (VEGF), also known as vascular permeability factor [20], may increase barrier permeability and disturb barrier function [21-23].”
BackgroundHuang, Y., Mao, Y. Q., Li, H., Shen, G., & Nan, G. (2018) · Biochemistry and Cell Biology · doi:10.1139/bcb-2017-0291 · Cited by 40
Prodjohardjono, A., Vidyanti, A. N., Susianti, N. A., Sudarmanta, Sutarni, S., & Setyopranoto, I. (2020) · PLoS ONE · doi:10.1371/journal.pone.0239370 · Cited by 39
“Intravenous administration of VEGF given at 48 hours after ischemia showed attenuation of neurobehavioral function in rats [16].”
MethodRole of diabetes in stroke: Recent advances in pathophysiology and clinical management
Bradley, S., Spring, K. J., Beran, R. G., Chatzis, D., Killingsworth, M. C., & Bhaskar, S. M. M. (2021) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3495 · Cited by 42
“leakage and haemorrhagic transformation, in the early phase of hyper‐acute stroke (1 h), and aids angiogenesis in the ischaemic penumbra in the subacute post‐stroke phase (48 h).(76) This is important as BBB disruption can cause parenchymal damage.”
BackgroundHaris, M., Husain, N., Singh, A. K., Husain, M., Srivastava, S., Srivastava, C., Behari, S., Rathore, R. K. S., Saksena, S., & Gupta, R. K. (2008) · Journal of Computer Assisted Tomography · doi:10.1097/rct.0b013e31816200d1 · Cited by 40
“It has been reported that high VEGF expression in enhancing tumor is associated with increased BBB permeability.(42,43) Earlier, Maia et al(44) have reported high VEGF expression in nonenhancing HGA as well as LGA.”
BackgroundInhibition of integrin αvβ3 reduces blood–brain barrier breakdown in focal ischemia in rats
Shimamura, N., Matchett, G. A., Solaroğlu, İ., Tsubokawa, T., Ohkuma, H., & Zhang, J. H. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21073 · Cited by 40
“Several studies have shown that VEGF worsens early outcomes in focal ischemia (Zhang et al., 2000; Kaya et al., 2005) and that VEGF is up-regulated immediately after ischemic stroke (Fig.”
BackgroundRole of blood vessels in the neuronal migration
Saghatelyan, A. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.04.006 · Cited by 45
Neuroprotection and neuroplasticity – A holistic approach and future perspectives
Muresanu, D. F. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.041 · Cited by 42
“Vascular endothelial growth factor (VEGF) exacerbates cerebral edema in the acute phase after a stroke and is responsible for vascular remodelling in the late phase [23].”
BackgroundRen, C., Wang, B. Z., Li, N., Jin, K., & Ji, X. (2015) · Aging and Disease · doi:10.14336/ad.2014.1126 · Cited by 39
“Intravenous VEGF-A also increased microvessel density in the cortical ischemia penumbra [36].”
BackgroundPark, H. W., Moon, H.-E., Kim, H. R., Paek, S. L., Kim, Y., Chang, J. W., Yang, Y. S., Kim, K., 오원일, Hwang, J. H., et al. (2015) · Journal of Neuroscience Research · doi:10.1002/jnr.23616 · Cited by 39
“…ischemia, topical administration of VEGF to the brain surface reduces the infarct size (Hayashi et al., 1998), intravenous application of VEGF improves neurological outcome (Zhang et al., 2000), and intraparenchymal administration of the anti-VEGF Ab increases the infarct size (Bao et al., 1999).”
BackgroundMolecular and Cellular Responses to Interleukin-4 Treatment in a Rat Model of Transient Ischemia
Lively, S. S., Hutchings, S., & Schlichter, L. C. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw081 · Cited by 40
“VEGF-A regulates angiogenesis, vascular permeability (64), neutrophil transmigration (42, 43), and increases blood vessel leakiness after ischemia (65).”
BackgroundLin, R., Cai, J., Kenyon, L. C., Iozzo, R. V., Rosenwasser, R. H., & Iacovitti, L. (2018) · Stem Cells · doi:10.1002/stem.2947 · Cited by 40
Stowe, A. M., Plautz, E. J., Nguyen, P., Frost, S. B., Eisner‐Janowicz, I., Barbay, S., Dancause, N., Sensarma, A., Taylor, M. D., Zoubina, E. V., et al. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600560 · Cited by 38
“One transcriptional target of post-stroke HIF-1a is the gene encoding VEGF, which has been implicated in the post-stroke recovery processes of angiogenesis and neuroprotection (Sun et al, 2003; Wang, 2003; Zhang et al, 2000).”
BackgroundProtective effect of albumin on VEGF and brain edema in acute ischemia in rats
Yao, X., Miao, W., Li, M., Wang, M., Ma, J., Wang, Y., Li, M., & Feng, H. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.02.002 · Cited by 39
Wang, W., Dong, J., Liu, X., Wang, Y., Ying, G. X., Ni, Z.-M., & Zhou, C. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.04.064 · Cited by 39
Komitova, M., Johansson, B. B., & Eriksson, P. S. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.03.010 · Cited by 39
Stankovic, I., Notaras, M. J., Wolujewicz, P., Lu, T. M., Lis, R., Ross, M. E., & Colak, D. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02740-2 · Cited by 38
“Both CTRL and SCZ iPSCs successfully yielded pure BMECs (Fig.”
BackgroundActivation of estrogen receptor β reduces blood–brain barrier breakdown following ischemic injury
Shin, J. A., Yang, S., Jeong, S. I., Park, H. J., Choi, Y., & Park, E. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.031 · Cited by 40
Dynamic regulation of aquaporin-4 water channels in neurological disorders
Hsu, Y., Tran, M., & Linninger, A. A. (2015) · Croatian Medical Journal · doi:10.3325/cmj.2015.56.401 · Cited by 38
Kim, E., Yang, J., Park, K. W., & Cho, S. (2017) · Translational Stroke Research · doi:10.1007/s12975-017-0601-z · Cited by 38
Vila, E., Solé, M., Masip, N., Puertas-Umbert, L., Amaro, S., Dantas, A. P., Unzeta, M., D’Ocón, P., Planas, A. M., Chamorro, Á., et al. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.04.002 · Cited by 38
“Among them, the human VEGF-A is a Janus-faced molecule, since together with its proangiogenic and neuroprotective effects, it disrupts the BBB integrity, leading to edema, hemorrhage, and brain damage [[4], [13], [14], [15]].”
BackgroundThe role of non-coding RNAs in neuroprotection and angiogenesis following ischemic stroke
Heydari, E., Alishahi, M., Ghaedrahmati, F., Winlow, W., Khoshnam, S. E., & Anbiyaiee, A. (2019) · Metabolic Brain Disease · doi:10.1007/s11011-019-00485-2 · Cited by 39
Liu, Y., Xue, Q., Li, A., Li, K., & Qin, X. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.112688 · Cited by 38
Astrocyte Gliotransmission in the Regulation of Systemic Metabolism
Murat, C. D. B., & García‐Cáceres, C. (2021) · Metabolites · doi:10.3390/metabo11110732 · Cited by 38
Experimental therapy with tissue kallikrein against cerebral ischemia
Chao, J. (2006) · Frontiers in bioscience · doi:10.2741/1886 · Cited by 38
VEGF regulates the blood‑brain barrier through MMP‑9 in a rat model of traumatic brain injury
Wu, M., Gong, Y., Jiang, L., Zhang, M., Gu, H., Shen, H., & Dang, B. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11664 · Cited by 37
Endothelial Cells and Astrocytes: A Concerto en Duo in Ischemic Pathophysiology
Bérézowski, V., Fukuda, A. M., Cecchelli, R., & Badaut, J. (2012) · International Journal of Cell Biology · doi:10.1155/2012/176287 · Cited by 37
“Perlecan domain V increased expression of vascular endothelial growth factor (VEGF), thus promoting angiogenesis, and interestingly did not lead to increased BBB permeability [73] even though VEGF is known to increase BBB permeability after ischemia [74].”
BackgroundZhu, M., Bi, X., Jia, Q., & Shangguan, S. (2009) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2009.08.005 · Cited by 36
Vascular endothelial growth factor in neonates with perinatal asphyxia
Aly, H. Z., Hassanein, S. M. A., Nada, A., Mohamed, M. H., Atef, S. H., & Atiea, W. (2008) · Brain and Development · doi:10.1016/j.braindev.2008.09.004 · Cited by 37
“Thus, a proposed therapeutic regimen could potentially consist of the early inhibition of VEGF function to minimize the formation of brain edema, followed by later active VEGF treatment leading to angiogenesis and neuro-protection [25].”
BackgroundXiao, X., Mruk, D. D., Wong, E. W. P., Lee, W. M., Han, D., Wong, C. K. C., & Cheng, C. Y. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00176.2014 · Cited by 37
“To corroborate this, c-Yes-knockout mice, although fertile, have defects in pIgApIgR transcytosis (21, 39), whereas in c-Src-knockout mice, which are infertile (14), VEGF, which is known to promote blood-brain barrier leakage (53), fails to compromise the blood-brain barrier (14).”
BackgroundZhou, Y., Li, P., Wu, J., Haslam, J., Mao, L., Xia, Y., He, Q., Wang, X., Lei, H. C., Lan, X., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.06.003 · Cited by 37
Inflammatory Markers and Severity of Intracerebral Hemorrhage
Bernstein, J. E., Savla, P., Dong, F., Zampella, B., Wiginton, J., Miulli, D. E., Wacker, M. R., & Menoni, R. (2018) · Cureus · doi:10.7759/cureus.3529 · Cited by 37
Kunze, R., & Marti, H. H. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.03.004 · Cited by 38
Meng, Z., Li, M., He, Q., Jiang, S. S., Zhang, X., Xiao, J.-F., & Bai, Y. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.02.036 · Cited by 37
“Late restoration of cerebral microcirculatory flow may involve increased collateral circulation and angiogenesis in the penumbra (Zhang et al., 2000; Zhang and Chopp, 2002; Nishimura et al., 2010).”
Basic Mechanisms in Intracranial Large-Artery Atherosclerosis: Advances and Challenges
Arenillas, J. F., & Álvarez‐Sabín, J. (2005) · Cerebrovascular Diseases · doi:10.1159/000089359 · Cited by 37
CREB activation mediates VEGF‐A’s protection of neurons and cerebral vascular endothelial cells
Lee, H., Chang, Y., Tu, Y., & Huang, C. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06584.x · Cited by 36
Metadata
- 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
- Venue
- Journal of Clinical Investigation
- Published
- 2000-10-01
- Volume
- 106
- Issue
- 7
- Pages
- 829-838
- ISSN
- 0021-9738 (ISSN-L)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
