Cited by 296Barrier Structure and Function StudiesTraumatic Brain Injury and Neurovascular DisturbancesAcute Ischemic Stroke Management

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Blood−brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury

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Prakash, Roshini, Carmichael, S. Thomas·2015·Current Opinion in Neurology

DOI 10.1097/wco.0000000000000248PMC PMC5267616

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Abstract

PURPOSE OF REVIEW: Angiogenesis or vascular reorganization plays a role in recovery after stroke and traumatic brain injury (TBI). In this review, we have focused on two major events that occur during stroke and TBI from a vascular perspective - what is the process and time course of blood-brain barrier (BBB) breakdown? and how does the surrounding vasculature recover and facilitate repair? RECENT FINDINGS: Despite differences in the primary injury, the BBB changes overlap between stroke and TBI. Disruption of BBB involves a series of events: formation of caveolae, trans and paracellular disruption, tight junction breakdown and vascular disruption. Confounding factors that need careful assessment and standardization are the severity, duration and extent of the stroke and TBI that influences BBB disruption. Vascular repair proceeds through long-term neovascularization processes: angiogenesis, arteriogenesis and vasculogenesis. Enhancing each of these processes may impart beneficial effects in endogenous recovery. SUMMARY: Our understanding of BBB breakdown acutely after the cerebrovascular injury has come a long way; however, we lack a clear understanding of the course of BBB disruption and BBB recovery and the evolution of individual cellular events associated with BBB change. Neovascularization responses have been widely studied in stroke for their role in functional recovery but the role of vascular reorganization after TBI in recovery is much less defined.

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Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., de Ferranti, S., Després, J.-P., Fullerton, H. J., Howard, V. J., et al. (2015) · Circulation · doi:10.1161/cir.0000000000000152 · Cited by 5,797
Angiogenesis in health and disease
Carmeliet, P. (2003) · Nature Medicine · doi:10.1038/nm0603-653 · Cited by 4,379
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Pericytes regulate the blood–brain barrier
Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. (2010) · Nature · doi:10.1038/nature09522 · Cited by 2,843
Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452
Traumatic brain injury
Ghajar, J. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02689-1 · Cited by 2,244
Pathophysiology of traumatic brain injury
Werner, C., & Engelhard, K. (2007) · British Journal of Anaesthesia · doi:10.1093/bja/aem131 · Cited by 1,712
Animal models of traumatic brain injury
Xiong, Y., Mahmood, A., & Chopp, M. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3407 · Cited by 1,456
The New Neurometabolic Cascade of Concussion
Giza, C. C., & Hovda, D. A. (2014) · Neurosurgery · doi:10.1227/neu.0000000000000505 · Cited by 1,353
The Neurometabolic Cascade of Concussion.
Giza, C. C., & Hovda, D. A. (2001) · PubMed Central · Cited by 1,342

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Background
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Background
Donepezil ameliorates oxygen-glucose deprivation/reoxygenation-induced brain microvascular endothelial cell dysfunction via the SIRT1/FOXO3a/NF-κB pathways
Sun, X., & Liu, B. (2022) · Bioengineered · doi:10.1080/21655979.2022.2045833 · Cited by 17
“Additionally, the damage of BBB results in a marked increase in paracellular permeability at the level of the cerebral microvasculature [40,41].”
Background
Longitudinal dynamics of microvascular recovery after acquired cortical injury
Lin, X., Chen, L., Jullienne, A., Zhang, H., Salehi, A., Hamer, M., Holmes, T. C., Obenaus, A., & Xu, X. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01361-4 · Cited by 17
C-Reactive Protein (CRP): A Potent Inflammation Biomarker in Psychiatric Disorders
Orsolini, L., Pompili, S., & Volpe, U. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-19-7376-5_7 · Cited by 19
Systems-level computational modeling in ischemic stroke: from cells to patients
Li, G., Zhao, Y., Ma, W., Gao, Y., & Zhao, C. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1394740 · Cited by 18
“Following the onset of ischemic stroke, the blood-brain barrier is compromised, resulting in increased permeability which allows metabolic by-products to in ﬁ ltrate the central nervous system and cause damage to neural cells (Abbott et al., 2010; Prakash and Carmichael, 2015).”
Background
Cytotoxic and Vasogenic Brain Edema
Keep, R. F., Andjelkovic, A. V., & Xi, G. (2017) · Primer on Cerebrovascular Diseases · doi:10.1016/b978-0-12-803058-5.00029-1 · Cited by 16
A Novel Histological Technique to Assess Severity of Traumatic Brain Injury in Rodents: Comparisons to Neuroimaging and Neurological Outcomes
Frank, D., Gruenbaum, B. F., Shelef, I., Zvenigorodsky, V., Binyamin, Y., Shapoval, O. M., Gal, R., Zlotnik, A. A., Melamed, I., & Boyko, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.733115 · Cited by 16
“It should also be mentioned that this parameter is influenced by many factors, including the size of the brain (Yushmanov et al., 2002; Purushotham et al., 2015), brain region (Yuan et al., 2017), model of the disease under study (Bardutzky et al., 2005; Albrecht et al., 2019) and age-related…”
Background
Exosomes: an innovative therapeutic target for cerebral ischemia-reperfusion injury
Yang, Y., Duan, Y., Yue, J., Yin, Y., Ma, Y., Wan, X., & Shao, J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1552500 · Cited by 15
“This surge in ROS causes oxidative damage to neurons, worsening brain injury, and cerebral infarction (Prakash and Carmichael, 2015; Yang Y. et al., 2015).”
A novel phosphodiesterase 9A inhibitor LW33 protects against ischemic stroke through the cGMP/PKG/CREB pathway
You, J.-Y., Liu, X., Bao, Y.-X., Shen, Z.-N., Wang, Q., He, G.-Y., Lü, J., Zhang, J., Chen, J., & Liu, P. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174987 · Cited by 15
Endothelial progenitor cell transplantation restores vascular injury in mice after whole-brain irradiation
Huang, X., Li, M., Zhou, D., Deng, Z., Guo, J., & Huang, H. (2020) · Brain Research · doi:10.1016/j.brainres.2020.147005 · Cited by 16
PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD
Keasey, M. P., Razskazovskiy, V., Jia, C., Peterknecht, E., Bradshaw, P. C., & Hagg, T. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00794-z · Cited by 15
“Brain endothelial cells have very high concentrations of mitochondria [35, 36], which are important for maintaining the blood–brainbarrier [37, 38].”
Background
Ulinastatin alleviates traumatic brain injury by reducing endothelin-1
Liu, T., Liao, X., & Zhou, M.-T. (2020) · Translational Neuroscience · doi:10.1515/tnsci-2021-0001 · Cited by 15
“TBI-associated brain edema is connectedwith increased expression of aquaporin-4 at the site of injury [5]; however, how aquaporin-4 contributes to the”
Background
Glycosaminoglycan scaffolding and neural progenitor cell transplantation promotes regenerative immunomodulation in the mouse ischemic brain
McCrary, M. R., Jiang, M. Q., Jesson, K., Gu, X., Logun, M. T., Wu, A., Gonsalves, N., Karumbaiah, L., Yu, S. P., & Wei, L. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114177 · Cited by 15
Contribution of Direct Cerebral Vascular Transport in Brain Substance Clearance
Wen, Q., Wang, H., Haacke, E. M., Jiang, Q., & Hu, J. (2023) · Aging and Disease · doi:10.14336/ad.2023.0426 · Cited by 14
Revolutionizing Stroke Care: Nanotechnology-Based Brain Delivery as a Novel Paradigm for Treatment and Diagnosis
Balaji, P. G., Bhimrao, L. S., & Yadav, A. K. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04215-3 · Cited by 17
“Oxidative stress triggered by ischemic events further exacerbates BBB permeability, with decreased expression of tight junction proteins in stroke [41].”
Four‐hour‐delayed 3D ‐ FLAIR MRIs in patients with acute unilateral peripheral vestibulopathy
Kim, K., Park, S., Lee, S., Park, E., Kim, B., Kim, B., & Kim, J. (2024) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.52123 · Cited by 14
Histochemistry of microinfarcts in the mouse brain after injection of fluorescent microspheres into the common carotid artery
Bai, W., Shen, Y., Yao, M., Su, Y., Xu, D., Wang, J., Wang, G.-R., Cui, J., & Zhang, J. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.322470 · Cited by 14
“, 2021), therefore it is reasonable to examine the alteration of the cellular components of the BBB or NVU with a vascular blockage model (Abbott et al., 2006; Prakash and Carmichael, 2015; Jiang et al., 2018; Freitas-Andrade et al., 2020).”
Background
Blood-brain barrier permeability for the first 24 hours in hypoxic-ischemic brain injury following cardiac arrest
You, Y., Park, J. S., Min, J. H., Jeong, W., Ahn, H. J., In, Y. N., Jeon, S., Lee, J. K., & Kang, C. (2024) · Resuscitation · doi:10.1016/j.resuscitation.2024.110150 · Cited by 13
Oxygen-glucose deprivation in neurons: implications for cell transplantation therapies
Rizzo, S. A., Bartley, O. J. M., Rosser, A., & Newland, B. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102126 · Cited by 13
“For example, following ischaemic stroke, angiogenesis and functional vascularisation can take up to 21 days [32], hampering neurogenesis and neurite outgrowth [33].”
Background
Mild Traumatic Brain Injury Induces Time- and Sex-Dependent Cerebrovascular Dysfunction and Stroke Vulnerability
Whitehead, B. J., Velazquez-Cruz, R., Albowaidey, A. A., Zhang, N., Karelina, K., & Weil, Z. M. (2022) · Journal of Neurotrauma · doi:10.1089/neu.2022.0335 · Cited by 13
“30,53 BBB function is critical to the regulation of cerebral vascular coagulation.”
Eveningness chronotype and depressive affective temperament associated with higher high-sensitivity C-reactive protein in unipolar and bipolar depression
Orsolini, L., Ricci, L., Pompili, S., Cicolini, A., & Volpe, U. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.04.004 · Cited by 14
Plasma brain‐derived tau correlates with cerebral infarct volume
González‐Ortiz, F., Holmegaard, L., Andersson, B., Brännmark, C., Blomstrand, C., Zetterberg, H., Jood, K., Blennow, K., Jern, C., & Stanne, T. M. (2024) · Journal of Internal Medicine · doi:10.1111/joim.20041 · Cited by 12
“Further, blood levels of BD-tau were established to be elevated in acute ischemic stroke patients compared to healthy controls [29], a likely reﬂection of neuronal death and BBB break-down following cerebral ischemia [17].”
Influential
Phased blood-brain barrier disruption in ischaemic stroke: implications for therapy?
Blase, A., di Girasole, C. G., Benjamin, L. A., & Turowski, P. (2025) · Fluids and Barriers of the CNS · doi:10.1186/s12987-025-00701-5 · Cited by 15
“Despite its complex pathophysiology, both clinical and experimental findings consistently highlight sustained oedema as a hallmark feature, contributing to dysfunction and destruction of neuronal tissue, neuroinflammation and adverse prognoses and clinical outcomes [94, 95].”
Proteomic profiling reveals age-related changes in transporter proteins in the human blood–brain barrier
Zhou, X., Azimi, M., Handin, N., Riselli, A. M., Vora, B., Chun, E., Dang, Z., Huang, E. J., Yee, S. W., Artursson, P., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-31224-6 · Cited by 13
VEGF mimic peptides: Potential applications in central nervous system therapeutics
D’Andrea, L. D., Rosa, L. D., Vigliotti, C., & Cataldi, M. (2016) · European Journal of Molecular & Clinical Medicine · doi:10.1016/j.nhtm.2016.12.002 · Cited by 12
Beta-caryophyllene in psychiatric and neurological diseases: Role of blood-brain barrier
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Safe focused ultrasound-mediated blood-brain barrier opening is driven primarily by transient reorganization of tight junctions
Noel, R. L., Kugelman, T., Karakatsani, M. E., Shahriar, S., Willner, M. J., Jimenez, D. A., Choi, C. S., Niimi, Y., Ji, R., Agalliu, D., et al. (2026) · Communications Engineering · doi:10.1038/s44172-026-00597-5 · Cited by 14
“D); however, BBB leakage in these vessels has been found in ischemic stroke and TBI leading to persistent brain damage 55,56 .”
Effect of low-frequency but high-intensity noise exposure on swine brain blood barrier permeability and its mechanism of injury
Wang, X., Lai, Y., Zhang, X., & Zhao, J. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.09.040 · Cited by 11
Neuroprotective and neuroregenerative potential of pharmacologically-induced hypothermia with D-alanine D-leucine enkephalin in brain injury
Liska, M., Crowley, M. G., Tuazon, J. P., & Borlongan, C. V. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.241427 · Cited by 11
“TBI and stroke have many post-injury cell death mechanisms in common, and thus the therapeutic research into one disorder state is often times applicable to the other (Sayeed and Stein, 2009; Albert-Weissenberger et al., 2013; Prakash and Carmichael, 2015).”
Background
Salvianolate lyophilized injection (SLI) strengthens blood-brain barrier function related to ERK1/2 and Akt signaling pathways
Zhao, C., Li, X., Li, X., Xu, Y., Ma, M., Wang, S., Chai, L., Guo, H. W., & Hu, L. (2019) · Brain Research · doi:10.1016/j.brainres.2019.06.014 · Cited by 11
Vascular Dysfunction after Modeled Traumatic Brain Injury Is Preserved with Administration of Umbilical Cord Derived Mesenchymal Stromal Cells and Is Associated with Modulation of the Angiogenic Response
Barretto, T. A., Park, E., Telliyan, T., Liu, E., Gallagher, D., Librach, C. L., & BAKER, A. J. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2021.0158 · Cited by 11
“This may reﬂect that, after injury, there are stronger signals that result in vasoconstriction and the effects related to post-injury edema 6 independent of the role of pericytes in maintaining vascular integrity. was associated with a reduction in cells expressing PDGFR-b as well as a loss of…”
Inhibition of Heat Shock Protein 90 Attenuates the Damage of Blood‐Brain Barrier Integrity in Traumatic Brain Injury Mouse Model
Zhang, J., Yao, J., Wang, K., Jiao, J., Xu, J., Shi, J., Ji, D., Lu, S., Li, X.-D., Zhang, Y., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5585384 · Cited by 10
“The damage of BBB was often found after TBI, cerebral ischemic stroke, and so on [18] which led to the formation of cerebral edema.”
In-vivo time course of organ uptake and blood-brain-barrier permeation of poly(L-lactide) and poly(perfluorodecyl acrylate) nanoparticles with different surface properties in unharmed and brain-traumatized rats
Bechinger, P., Serrano, L. E., Grützner, V., Musyanovych, A., Jussen, D., Krenzlin, H., Eldahaby, D., Riede, N., Kempski, O. S., Ringel, F. A., et al. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.994877 · Cited by 10
Perspective insights into versatile hydrogels for stroke: From molecular mechanisms to functional applications
Wu, X., Zhang, T., Jia, J., Chen, Y., Zhang, Y., Fang, Z., Zhang, C., Bai, Y., Li, Z., & Li, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116309 · Cited by 11
Complement C3 activation in the ICU: Disease and therapy as Bonnie and Clyde
Mannes, M., Mastellos, D. C., Ekdahl, K. N., Nilsson, B., Yancopoulou, D., Lambris, J. D., & Huber-Lang, M. S. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101640 · Cited by 11
Lipid nanoparticles hijack neutrophils for enhanced anti-inflammatory and stroke therapy
Cheng, Q., Zhang, Y., Su, G., Xue, Y., Zou, X., Syeda, M. Z., Jie, R., Wan, J., Yang, L., Bi, Q., et al. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.09.015 · Cited by 9
Mechanisms of Endothelial Injury and Blood–Brain Barrier Dysfunction in Stroke
Ronaldson, P. T., & Davis, T. P. (2017) · Primer on Cerebrovascular Diseases · doi:10.1016/b978-0-12-803058-5.00045-x · Cited by 9
Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown
Zhang, Y., Warden, A. R., Ahmad, K. Z., Liu, Y., He, X., Zheng, M.-Q., Huo, X., Zhi, X., Ke, Y., Li, H., et al. (2021) · Research · doi:10.34133/2021/9873545 · Cited by 9
“Central nervous system diseases, including brain injury, stroke [1, 2], brain tumors [3, 4], neurodegenerative diseases [5], and cognitive dysfunction associated with aging [6, 7], commonly occur via the destruction of the blood-brain barrier (BBB).”
Background
Systemic Oxidative Stress in Subacute Stroke Patients Undergoing Rehabilitation Treatment
Cocco, C., Siotto, M., Guerrini, A., Germanotta, M., Galluccio, C., Cipollini, V., Cortellini, L., Pavan, A., Lattanzi, S., Insalaco, S., et al. (2024) · Antioxidants · doi:10.3390/antiox13030354 · Cited by 10
“In this context, it is possible that the presence of systemic oxidative stress could contribute to further BBB and neuronal damage [54,55].”
Background

Authors: Prakash, R., & Carmichael, S. T.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Prakash, Roshini
ORCID: Prakash, Roshini
Carmichael, S. Thomas
Venue: Current Opinion in Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2015-12
Volume: 28
Issue: 6
Pages: 556-564
ISSN: 1350-7540 (ISSN-L)
DOI: 10.1097/wco.0000000000000248
PMC: PMC5267616
OpenAlex: W2341136898
Cited by: 296
References: 134
Citations by year: 2026: 16 · 2025: 27 · 2024: 32 · 2023: 29 · 2022: 33 · 2021: 38 · 2020: 36 · 2019: 31 · 2018: 24 · 2017: 19 · 2016: 11
FWCI: 1.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Current Opinion in Neurology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS081055, R01NS053957)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Keywords: blood-brain barrier disruption, neovascularization, stroke, traumatic brain injury, angiogenesis, arteriogenesis, vasculogenesis, vascular repair, caveolae, tight junction disruption, paracellular permeability, functional recovery
MeSH terms: Blood-Brain Barrier, Brain Injuries, Humans, Neovascularization, Physiologic, Stroke

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Blood−brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury

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