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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.
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“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]
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Shen, D., Ye, X., Li, J., Hao, X., Jin, L., Jin, Y., Tong, L., & Gao, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158552 · Cited by 18
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“Angiogenic processes, possibly driven via VEGF signaling [67], coupled with reduced microglial activation patterns were found alongside pro-injury response signals, suggesting that patterns of damage and healing can occur simultaneously at the brain vasculature.”
BackgroundMonitoring Brain Repair in Stroke Using Advanced Magnetic Resonance Imaging
Sztriha, L., Tuura, R., Modo, M., Barker, G. J., Williams, S., & Kalra, L. (2012) · Stroke · doi:10.1161/strokeaha.111.649244 · Cited by 17
“Angiogenic vessels are permeable during the early stages of development and become less leaky as they mature, potentially allowing new vessels to be distinguished by imaging techniques.(10)”
BackgroundElevation of Autoantibody in Patients with Ischemic Stroke
Yoshida, Y., Hiwasa, T., Machida, T., Kobayashi, E., Mine, S., Matsushima, J., Takiguchi, M., & Iwadate, Y. (2018) · Neurologia medico-chirurgica · doi:10.2176/nmc.ra.2018-0022 · Cited by 18
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“Besides, VEGF administration therapy in post-stroke patients can reduce the extent of cerebral infarction because VEGF will stimulate angiogenesis and neurogenesis in areas near the penumbra [27], [28].”
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Park, J., Seong, H., Jin, H.-B., & Kim, Y. (2016) · Biological Research For Nursing · doi:10.1177/1099800416686179 · Cited by 19
“In one study, researchers administered VEGF intravenously within 2 days after a stroke, which resulted in enhanced angiogenesis in the ischemic penumbra and significantly improved neurological recovery (Zhang et al., 2000).”
BackgroundInfluence of vascular endothelial growth factor on angiogenesis and neurogenesis
Rudko, A. S., Эфендиева, М. Х., Budzinskaya, M. V., & Karpilova, M. A. (2017) · Russian Annals of Ophthalmology · doi:10.17116/oftalma2017133375-80 · Cited by 18
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Permselectivity of Silk Fibroin Hydrogels for Advanced Drug Delivery Neurotherapies
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Retinal Neurovascular Coupling: From Mechanisms to a Diagnostic Window into Brain Disorders
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“Studies in the brain further show that following injury, such as stroke or brain tumors, increased VEGF expression enhances angiogenesis and promotes BBB, which is thought to represent an attempt to repair damaged tissue by enhancing blood supply and nutrient delivery to the affected area [61].”
Garvin, J., Semenikhina, M., Liu, Q., Rarick, K. R., Isaeva, E., Levchenko, V., Staruschenko, A., Palygin, O., Harder, D. R., & Cohen, S. S. (2022) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00315.2020 · Cited by 17
Molecular and anatomical roadmap of stroke pathology in immunodeficient mice
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“Additionally, it is well known that the growth of new capillaries carries the risk for immature vessel formation, which may enhance haemorrhagic transformation and BBB damage; and mature vessels are associated with better functional outcomes [15,35].”
BackgroundTang, L., Wang, D., Chang, H., Liu, Z., Zhang, X., Feng, X., & Han, L. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118372 · Cited by 17
Effects of integrins and integrin αvβ3 inhibitor on angiogenesis in cerebral ischemic stroke
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“In the case of VEGF and MMP, inhibition is only protective for a specific duration following injury, and should be stopped shortly after the acute insult in order to preserve the reparative effects of MMPs and VEGF in the more subacute phases of injury (Mandal et al., 2003; Zhang et al., 2000).”
BackgroundHypoxia-specific VEGF-expressing neural stem cells in spinal cord injury model
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Sokolov, M. E., Bashirov, F. V., Аршалуйсович, М. В., Povysheva, T. V., Fadeev, F., Izmailov, A., Kuztetsov, M. S., Safiullov, Z. Z., Шмаров, М. М., Naroditskyi, B. S., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00111 · Cited by 17
“Thus, VEGF during stroke recovery can support microvascular angiogenesis and may have powerful neuroprotective and neurorestorative effects in the ischemic brain, shown in numerous preclinical studies (Zhang et al., 2000).”
BackgroundThe Dynamics of Impaired Blood-Brain Barrier Restoration in a Rat Model of Co-morbid Injury
Amtul, Z., Yang, J., Nikolova, S., Lee, T., Bartha, R., & Cechetto, D. F. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0904-4 · Cited by 17
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Longitudinal dynamics of microvascular recovery after acquired cortical injury
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“Hemodynamic Improvement After MyoblastMediated VEGF Therapy Previous experimental VEGF gene-therapy studies for cerebral ischemia have mainly focused on the treatment of acute focal stroke and VEGF-induced angiogenesis has been shown to result in structural neuroprotection and functional recovery.(29,30) However, whet…”
Chen, D., Zhao, T., Ni, K., Dai, P., Yang, L., Xu, Y., & Li, F. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.03.074 · Cited by 17
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“A second effect of experimental induction of angiogenesis by VEGF is an increased permeability of the blood–brain barrier (Zhang et al., 2000) resulting in brain edema.”
BackgroundSystemic therapy for lung cancer brain metastases: a rationale for clinical trials.
Oh, Y. W., & Stewart, D. J. (2008) · PubMed · Cited by 17
Hansford, R., Buller, S. A., Tsang, A. H. K., Benoit, S., Roberts, A. G., Erskine, E., Brown, T., Pirro, V., Reimann, F. M., Harada, N., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.07.009 · Cited by 19
“VEGF is a well-known potent inducer of vascular hyperpermeability 44,45 .”
Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma
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“Mannitol and VEGF were injected continuously into the common iliac artery of adult rats for 30 min at 11 h after crush injury of the sciatic nerve (Zhang et al, 2000; Sun et al, 2012), followed by perfusion at 12 h after injury (Fig 3B).”
BackgroundMethodThe Association of Biochemical and Genetic Biomarkers in VEGF Pathway with Depression
Nunes, F. D. D., Ferezin, L. P., Pereira, S. C., Fígaro-Drumond, F. V., Pinheiro, L. C., Menezes, I. C., Baes, C. V. W., Coeli‐Lacchini, F. B., Tanus-Santos, J. E., Juruena, M. F., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14122757 · Cited by 17
“In cerebral ischemia, VEGF was able to increase the permeability of the BBB, causing subsequent edema [23,24].”
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“(Doeppner and Hermann, 2010; Grande et al., 2013; Wan et al., 2013) The first series of successful experiments for MSCs for the treatment of ischemic stroke was reported by Chopp’s group (Chen et al., 2000; Li et al., 2000; Zhang et al., 2000).”
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“Thus, VEGF administration during the acute phase of cerebral ischemia leads to increased edema, increased infarct volume, poor neurological outcomes, and increased mortality (2).”
BackgroundEffect of VEGF receptor antagonist (VGA1155) on brain edema in the rat cold injury model.
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“We also observed that 51/80 patients had a good outcome with NIHSS <15, and 29 patients had a poor outcome with NIHSS >15, which is in congruence with the other report in which 3/29 patients who expressed exceptionally high mean VEGF levels (>1000 pg/ml) presented with the highest improvements in SSS rating.[8] The RO…”
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“Th erefore, our data suggest that r-Hu-EPO may act directly on cerebral endothelial cells that secrete more and more VEGF and BDNF thereby, accelerating angiogenesis and the production of OPCs via a paracrine pathway.”
BackgroundCentral Nervous System Injury and Neuroprotection
Bonifacio, S. L., Gonzalez, F. F., & Ferriero, D. M. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0134-0.10061-7 · Cited by 16
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“after using VEGF in ischemic animal models (Zhang et al. 2000).”
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Bernocchi, F., Bonomi, C. G., Assogna, M., Moreschini, A., Mercuri, N. B., Koch, G., Martorana, A., & Motta, C. (2024) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2024.05.002 · Cited by 15
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“…constant low level of VEGF is necessary: insuÿcient VEGF levels can aect the integrity of the brain, particularly the mesolimbic structures, while abnormally elevated VEGF levels can promote BBB permeability and excessive formation of new leaky blood vessels (Wu et al., 2022; Zhang et al., 2000).”
Increased Expression of EMMPRIN and VEGF in the Rat Brain after Gamma Irradiation
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“VEGF-induced increases in microvessel permeability have been demonstrated not only in normal brain endothelial cells but also in disease conditions, such as in tissues surrounding brain tumors (14) and ischemia lesions (15).”
Huang, T., Chang, C., Chang, S., Lin, K., & Tsai, R. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15999 · Cited by 15
“Antagonism of VEGF has been shown to reduce ischemia/reperfusion-related brain edema and injury, implicating VEGF in the pathogenesis of stroke and related disorders.(30,31) However, in a rat model of focal cerebral embolic ischemia, the systemic administration of VEGF after a longer period (after 48 hours) was found…”
BackgroundIschemic Brain Injury and Hepatocyte Growth Factor
Takeo, S., Takagi, N., & Takagi, K. (2007) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.127.1813 · Cited by 15
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Perfusion and Permeability MRI Predicts Future Cavernous Angioma Hemorrhage and Growth
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“In addition, VEGF, which is expressed on macrophages, neurons, glia, and vascular endothelial cells, promotes angiogenesis during tissue repair [54], and because DPSCs are secreted in high numbers, the angiogenic effect of DPSCs may also be related to their protective effect in the brain.”
BackgroundCeccariglia, S., D’Altocolle, A., Fà, A. D., Silvestrini, A., Barba, M., Pizzolante, F., Repele, A., Michetti, F., & Gangitano, C. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.047 · Cited by 15
“…studies have shown that the VEGF/VEGFR-2 pathway can also increase vascular permeability, thereby disrupting the BBB, and promote inflammatory cell infiltration in the nervous system (Proescholdt et al., 1999; van Bruggen et al., 1999; Zhang et al., 2000; Kilic et al., 2006; Lafuente et al., 2006).”
BackgroundResultExtract of Ginkgo Biloba Promotes the Expression of VEGF Following Subarachnoid Hemorrhage in Rats
Sun, B., Hu, D., Yuan, H., Ye, W., Wang, X., Xia, Z., Zhang, S., & Wang, L. (2009) · International Journal of Neuroscience · doi:10.1080/00207450902815842 · Cited by 15
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“However, it has been proposed that, besides its beneficial effects, producing vasodilation and increased blood flow, eNOS is also involved in vascular endothelial growth factor (VEGF) induced vascular hyperpermeability [33], which contributes to disruption of the blood-brain barrier, resulting in vascular leakage [34,…”
BackgroundTargeted delivery of growth factors in ischemic stroke animal models
Rhim, T., & Lee, M. (2016) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1144588 · Cited by 17
“[8,34,35] VEGF facilitates new blood vessel formation in the ischemic region.”
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“Hypoxia-induced angiogenesis increases blood flow and oxygen delivery to ischemic tissues, which contributes to the recovery after stroke[28].”
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“Although VEGF has potent and diverse effects on endothelial cells and neurons, there are significant concerning effects of this agent, such us its actions on vasculature causing hyper-permeable capillaries and larger vessels with questionable functionality, changes on the ependymal cells and hydrocephalus in rodents,…”
BackgroundAPX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats
Yan, T., Venkat, P., Chopp, M., Zacharek, A., Yu, P., Ning, R., Qiao, X., Kelley, M. R., & Chen, J. (2018) · Aging and Disease · doi:10.14336/ad.2017.1130 · Cited by 15
“It has been previously demonstrated that in the acute phase of stroke in non-DM rodents, administration of VEGF enhances cerebral microvascular perfusion, increases BBB leakage, induces cerebral hemorrhage and expands infarction volume after stroke [78].”
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Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke
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The role of vascular endothelial growth factor in cerebral oedema formation.
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Hydrogels and Nanogels - Applications in Medicine
Umeyor, C., Uronnachi, E., & Kakade, P. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.1000374 · Cited by 14
Cuccurullo, S. J., Fleming, T. K., Petrosyan, H. A., Hanley, D. F., & Raghavan, P. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1376616 · Cited by 14
“For example, it was shown that increased VEGF levels are central to stimulating angiogenesis around the lesion and facilitating neurological recovery post-acute stroke (63, 64).”
BackgroundLi, K., Wang, K., Xu, S., Xie, X., Tang, Y., Zhang, L., & Liu, Z. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.09.073 · Cited by 14
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Cheng, L., Ma, L., Ren, H., Zhao, H., PANG, Y., Wang, Y., & WEI, M. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2520 · Cited by 14
“VEGF-induced increases in microvessel permeability have been demonstrated not only in normal brain endothelial cells, but also in diseased conditions, including in tissue surrounding brain tumors (27) and the ischemia lesion area (28).”
Gallego, I., Villate-Beitia, I., Soto‐Sánchez, C., Menéndez, M., Grijalvo, S., Eritja, R., Martı́nez, G., Humphreys, L., López-Méndez, T. B., Puras, G., et al. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.9b01213 · Cited by 15
VEGI Improves Outcomes in the Early Phase of Experimental Traumatic Brain Injury
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The Effects of Atorvastatin on Global Cerebral Ischemia-Induced Neuronal Death
Kho, A. R., Hong, D. K., Kang, B. S., Park, W.-J., Choi, K. C., Park, K., & Suh, S. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094385 · Cited by 16
“Under ischemic conditions, activated glial and endothelial cells produce cytokines and chemokines that induce lymphocyte migration across the BBB as well as enhance the permeability of the brain blood vessels; as a result, brain edema severely worsens, leading to neurological disorders [44,45].”
BackgroundNeuroprotection by the cannabidiol aminoquinone VCE-004.8 in experimental ischemic stroke in mice
Lavayen, B. P., Yang, C., Larochelle, J., Liu, L., Tishko, R. J., de Oliveira, A. C. P., Muñóz, E., & Candelario‐Jalil, E. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105508 · Cited by 14
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The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia
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“VEGF has been reported to reduce infarct size (Bellomo et al., 2003; Stowe et al., 2007; Stowe et al., 2008; Wang et al., 2005) and brain edema (Harrigan et al., 2002; Kimura et al., 2005; van Bruggen et al., 1999; Zhang et al., 2000) after cerebral ischemia.”
BackgroundMethodEffects of deferoxamine on blood–brain barrier disruption and VEGF in focal cerebral ischemia
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Shimamura, M. (2006) · Frontiers in bioscience · doi:10.2741/1833 · Cited by 15
“Similarly, late (48 hrs) intravenous administration of rhVEGF165 to ischemic rats also enhances angiogenesis in the ischemic penumbra and significantly improves neurological recovery (8).”
BackgroundLi, Z., Wang, R., Li, S., Wei, J., Zhang, Z., Li, G., Dou, W., Wei, Y.-K., & Feng, M. (2008) · Neurological Research · doi:10.1179/174313208x309720 · Cited by 14
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Vasogenic edema and VEGF expression in a rat two-vein occlusion model
Kimura, R., Nakase, H., Sakaki, T., Taoka, T., & Tsuji, T. (2003) · Springer eBooks · doi:10.1007/978-3-7091-0651-8_46 · Cited by 14
Autocrine VEGF drives neural stem cell proximity to the adult hippocampus vascular niche
Dause, T. J., Denninger, J. K., Osap, R., Walters, A. E., Rieskamp, J. D., Kirby, E. D., & Kirby, E. D. (2024) · Life Science Alliance · doi:10.26508/lsa.202402659 · Cited by 14
“In addition to its role in regulating endothelial migration and proliferation, VEGF also stimulates shedding of BBB associated proteins on endothelial cells, thereby increasing BBB permeability (Zhang et al, 2000).”
Shen, L., Ye, M., DING, X. S., HAN, Q., Zhang, C., Liu, X., Huang, H., Wu, E., Huang, H., & Gu, X. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.001 · Cited by 13
“Stem cells can differentiate into neural lineages to replace lost neurons (Zhang et al., 2000; Scotto-Lomassese et al., 2003), provide trophic support to neurons at risk near the infarct area and promote survival and differentiation of endogenous precursor cells after stroke (Chang et al., 2007),…”
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Gene therapy for stroke: 2006 overview
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“For example, delayed treatment (48 hours) using vascular endothelial growth factor (VEGF) resulted in neuroprotection after focal cerebral ischemia, whereas early administration (1 hour) induced edema [9].”
BackgroundMa, C., Zhou, J., Xu, X., Wang, L., Qin, S., Hu, C., Nie, L., & Tu, Y. (2019) · Medical Science Monitor · doi:10.12659/msm.917537 · Cited by 13
“A previous study also reported that treatment of rats in the early stage of cerebral ischemia with VEGF protein can increase blood-brain barrier permeability and even cerebral hemorrhage, whereas the use of VEGF inhibitors can reduce blood-brain barrier permeability [13].”
BackgroundIslamov, R. R., Bashirov, F. V., Sokolov, M. E., Izmailov, A., Fadeev, F., Аршалуйсович, М. В., Davleeva, M., Zubkova, O. V., Smarov, M. M., Logunov, D. Y., et al. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.290902 · Cited by 13
“The expression of VEGF, as a neuroprotective and angiogenic factor (Zhang et al., 2000), and NCAM in WBCs is proposed to increase homing of the gene-modified leucocytes in the CNS (Islamov et al.”
BackgroundZhuang, H., Wang, H., Yang, H., & Li, H. (2020) · Cancer Management and Research · doi:10.2147/cmar.s259077 · Cited by 13
RetractedLi, N., Zhang, X., Zhai, J., Yin, J., Ma, K., Wang, R., Qin, X., Li, Y., Dong, X.-W., & Wang, S. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114028 · Cited by 13
Myagmar, B.-O., Chen, R., Zhang, X., Xu, R., Jiang, W., Cao, W., Ji, H., & Zhang, X. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120568 · Cited by 13
Testai, F. D., Aiyagari, V., Hillmann, M. L., Amin‐Hanjani, S., Dawson, G., & Gorelick, P. B. (2011) · Neurocritical Care · doi:10.1007/s12028-011-9559-y · Cited by 13
“Alternatively, it has been proposed that VEGF is neuroprotective against cerebrovascular injury as it induces vascular sprouting and angiogenesis, increases brain plasticity, and enhances vascular relaxation probably by boosting endothelial NO levels [22–24].”
BackgroundCheng, D., Lo, C., & Sefton, M. V. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31716 · Cited by 13
Placental growth factor: a tissue modelling factor with therapeutic potentials in neurology?
Chaballe, L., Schoenen, J. E., & Franzen, R. (2011) · PubMed · Cited by 13
Zhao, J., Bai, Y., Jin, L., Weng, Y., Wang, Y., Wu, H., Li, X., Huang, Y., & Wang, S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172709 · Cited by 13
“For example, intravenous VEGF increases microvessel density in the cortical ischemia penumbra [13], and intracerebroventricular VEGF enhances the delayed survival of newborn neurons in the dentate gyrus and subventricular zone [14].”
Baek, S. J., Hammock, B. D., Hwang, I. K., Li, Q. X., Moustaïd‐Moussa, N., Park, Y., Safe, S. H., Suh, N., Yi, S.-S., Zeldin, D. C., et al. (2021) · Nutrients · doi:10.3390/nu13061881 · Cited by 15
“Vascular endothelial growth factor (VEGF) is one of the angiogenic factors in vascular endothelial cells, enhancing vascular permeability in the brain after ischemia [137,138].”
BackgroundBiotechnology-based therapeutics for management of cerebral stroke
Patel, D., & Wairkar, S. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174638 · Cited by 13
Angiogenesis Dysregulation in Term Asphyxiated Newborns Treated with Hypothermia
Shaikh, H., Boudes, E., Khoja, Z., Shevell, M. I., & Wintermark, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128028 · Cited by 13
“VEGF-C expression was decreased in all asphyxiated newborns, which may represent a mechanism for protecting against vascular permeability-related edema [46–48].”
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Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic brain injury
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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
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