The DOI matches its Crossref record; 52 of the 54 references it cites were found in a registry or an index.
Reversal of West Nile virus-induced blood–brain barrier disruption and tight junction proteins degradation by matrix metalloproteinases inhibitor
Open accessAbstract
Though compromised blood-brain barrier (BBB) is a pathological hallmark of WNV-associated neurological sequelae, underlying mechanisms are unclear. We characterized the expression of matrix metalloproteinases (MMP) in WNV-infected human brain microvascular endothelial cells (HBMVE) and human brain cortical astrocytes (HBCA), components of BBB and their role in BBB disruption. Expression of multiple MMPs was significantly induced in WNV-infected HBCA cells. Naïve HBMVE cells incubated with the supernatant from WNV-infected HBCA cells demonstrated loss of tight junction proteins, which were rescued in the presence of MMP inhibitor, GM6001. Further, supernatant from WNV-infected HBCA cells compromised the in vitro BBB model integrity. Our data suggest astrocytes as one of the sources of MMP in the brain, which mediates BBB disruption allowing unrestricted entry of immune cells into the brain, thereby contributing to WNV neuropathogenesis. Because of the unavailability of WNV antivirals and vaccines, use of MMP inhibitors as an adjunct therapy to ameliorate WNV disease progression is warranted.
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“Viral infections in general downregulate TJ proteins and promote chemokine production and vascular cell adhesion molecule 1 (VCAM-1) expression in brain endothelial cells, thereby weakening the BBB and facilitating entry into the brain (5, 212, 399, 613).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [613]
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Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis
Wang, T., Town, T., Alexopoulou, L., Anderson, J. F., Fikrig, E., & Flavell, R. A. (2004) · Nature Medicine · doi:10.1038/nm1140 · Cited by 1,142
Blood–brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions
Persidsky, Y., Ramirez, S. H., Haorah, J., & Kanmogne, G. D. (2006) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-006-9025-3 · Cited by 922
Matrix metalloproteinases in neuroinflammation
Rosenberg, G. A. (2002) · Glia · doi:10.1002/glia.10108 · Cited by 868
Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases
Hu, J., den Steen, P. E. V., Sang, Q. A., & Opdenakker, G. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2308 · Cited by 806
Multiple roles for MMPs and TIMPs in cerebral ischemia
Cunningham, L. A., Wetzel, M. K., & Rosenberg, G. A. (2005) · Glia · doi:10.1002/glia.20169 · Cited by 412
West Nile Virus: Epidemiology and Clinical Features of an Emerging Epidemic in the United States
Hayes, E. B., & Gubler, D. J. (2005) · Annual Review of Medicine · doi:10.1146/annurev.med.57.121304.131418 · Cited by 366
Junctional complexes of the blood–brain barrier: permeability changes in neuroinflammation
Petty, M. A., & Lo, E. H. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00128-4 · Cited by 361
Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia
Rosenberg, G. A., & Yang, Y. R. (2007) · Neurosurgical FOCUS · doi:10.3171/foc.2007.22.5.5 · Cited by 358
A model for monocyte migration through the blood-brain barrier during HIV-1 encephalitis
Persidsky, Y., Stins, M. F., Way, D., Witte, M., Weinand, M. E., Kim, K. S., Bock, P., Gendelman, H. E., & Fiala, M. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.7.3499 · Cited by 316
Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke
Anthony, D. C., Ferguson, B., Matyzak, M. K., Miller, K., Esiri, M. M., & Perry, V. H. (1997) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1997.tb01315.x · Cited by 268
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Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
Modern methods for delivery of drugs across the blood–brain barrier
Chen, Y., & Liu, L. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.11.010 · Cited by 1,038
Virus Infections in the Nervous System
Koyuncu, O. O., Hogue, I. B., & Enquist, L. W. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.03.010 · Cited by 594
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Suthar, M. S., Diamond, M., & Gale, M. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2950 · Cited by 432
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Metadata
- Authors
- Verma, S., Kumar, M., Gurjav, U., Lum, S., & Nerurkar, V. R.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- Corresponding author
- Nerurkar, Vivek R.
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 397
- Issue
- 1
- Pages
- 130-138
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC3102050
- OpenAlex
- W1968754528
- Cited by
- 151
- References
- 54
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 14 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 5 · 2015: 15 · 2014: 14 · 2013: 9 · 2012: 16
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1262 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Virology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Hawaii Community Foundation (20050405)
- Research Centers in Minority Institutions Program (G12RR003061)
- Centers of Biomedical Research Excellence (P20RR018727)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- West Nile virus, blood-brain barrier disruption, matrix metalloproteinases, tight junction proteins, astrocytes, brain microvascular endothelial cells, GM6001, matrix metalloproteinase inhibitors, neuroinflammation
- MeSH terms
- Astrocytes, Blood-Brain Barrier, Dipeptides, Humans, Membrane Proteins, Phosphoproteins, Protease Inhibitors, West Nile virus, Tight Junctions, Matrix Metalloproteinases, Gene Expression Profiling, Endothelial Cells, Matrix Metalloproteinase Inhibitors, Claudin-1, Zonula Occludens-1 Protein
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