The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Imaging matrix metalloproteinase activity in multiple sclerosis as a specific marker of leukocyte penetration of the blood-brain barrier
Abstract
The enzymes gelatinase A/matrix metalloproteinase-2 (MMP-2) and gelatinase B/MMP-9 are essential for induction of neuroinflammatory symptoms in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS); in the absence of these enzymes, the disease does not develop. We therefore investigated the cellular sources and relative contributions of MMP-2 and MMP-9 to disease at early stages of EAE induction. We demonstrated that MMP-9 from an immune cell source is required in EAE for initial infiltration of leukocytes into the central nervous system and that MMP-9 activity is a reliable marker of leukocyte penetration of the blood-brain barrier. We then developed a molecular imaging method to visualize MMP activity in the brain using fluorescent- and radioactive-labeled MMP inhibitors (MMPis) in EAE animals and used the radioactive MMP ligand for positron emission tomography (PET) imaging of MMP activity in patients with MS. In contrast to traditional T1-gadolinium contrast-enhanced MRI, MMPi-PET enabled tracking of MMP activity as a unique feature of early lesions and ongoing leukocyte infiltration. MMPi-PET therefore allows monitoring of the early steps of MS development and provides a sensitive, noninvasive means of following lesion formation and resolution in murine EAE and human MS.
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“Recent studies using radioactive MMP PET found that increased MMP activity localizes around active lesions that associate with leukocyte infiltration (201).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [201]
Citations
Cites
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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
Astrocytes induce blood–brain barrier properties in endothelial cells
Janzer, R. C., & RAFF, M. C. (1987) · Nature · doi:10.1038/325253a0 · Cited by 1,613
The impact of the extracellular matrix on inflammation
Sorokin, L. M. (2010) · Nature reviews. Immunology · doi:10.1038/nri2852 · Cited by 955
Self-citationMatrix 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
Self-citationAgrawal, S., Anderson, P., Durbeej, M., van Rooijen, N., Ivars, F., Opdenakker, G., & Sorokin, L. M. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051342 · Cited by 559
Self-citationSixt, M., Engelhardt, B., Pausch, F., Hallmann, R., Wendler, O., & Sorokin, L. M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.933 · Cited by 504
Self-citationWolburg, H., Wolburg‐Buchholz, K., Kraus, J., Rascher-Eggstein, G., Liebner, S., Hamm, S., Duffner, F., Grote, E.-H., Risau, W., & Engelhardt, B. (2003) · Acta Neuropathologica · doi:10.1007/s00401-003-0688-z · Cited by 454
Targeting leukocyte MMPs and transmigration
Brundula, V., Rewcastle, N. B., Metz, L. M., Bernard, C. C. A., & Yong, V. W. (2002) · Brain · doi:10.1093/brain/awf133 · Cited by 427
Mahad, D., & Ransohoff, R. M. (2002) · Seminars in Immunology · doi:10.1016/s1044-5323(02)00125-2 · Cited by 412
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Research works printed but not linked: 1
- Gijbels K., Steinman L., Gelatinase B producing cells in multiple sclerosis lesions. J. Cell. Biochem. Suppl. 18D, 143 (1994).
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Molecular Imaging of Immunity and Inflammation and Its Impact on Precision Medicine
Wildgruber, M., & Eisenblätter, M. (2021) · Biomedicines · doi:10.3390/biomedicines9010062 · Cited by 1
Onwuha-Ekpete, L. C., & Fields, G. (2022) · Peptide Science · doi:10.1002/pep2.24262
Positron emission tomography imaging of neuroinflammation
(2023) · Advances in magnetic resonance technology and applications · doi:10.1016/b978-0-323-91771-1.00007-1
Anatomy and Microanatomy of Immune Tissues Central Nervous System: Microanatomy
Hannocks, M., Song, J., Burmeister, M., Gerwien, H., Kapupara, K., Samawar, S.-K., Deshpande, T., & Sorokin, L. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-128-24465-4.00007-7
Self-citationThe blood-brain barrier in multiple sclerosis
Zierfuss, B., Charabati, M., MacVicar, B. A., Zandee, S., & Prat, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-823848-6.00011-7
Matrix metallopeptidase-9/gelatinase B
Opdenakker, G., Ugarte-Berzal, E., & Vandooren, J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-28849-4.00094-1
Self-citationSun, H., Ma, D., Zhang, W., Hou, S., Chen, Z., Li, X., Meng, H., & Zhang, D. (2025) · Epilepsia Open · doi:10.1002/epi4.70056
The effects of bacterial and viral infections on microglia
Ermolina, S., & Bowdish, D. M. E. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27340-7.00001-2
Internalization of myelin debris by neutrophils fuels inflammationPreprint
Bondt, M. D., Renders, J., Sterckx, Y., Vandendriessche, S., Broeckhoven, J. V., Berends, A. V. D. W., Pörtner, N., Vanbrabant, L., de Oliveira, V. L. S., Bogie, J. F. J., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9810204/v1
Leukocyte–endothelial interactions and brain capillary function in neurological diseases
Lim, H., Shih, A. Y., & Gust, J. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261441983 · Cited by 1
Mu, Y., Wen, K., Zhou, L., Gu, Z., Wang, T., Li, Y., Yang, X., Liu, X., Zhang, X., Chi, W., et al. (2026) · ACS Nano · doi:10.1021/acsnano.6c11475
Self-citationRagunath, M., Ardra, S., Balde, A., & Nazeer, R. A. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02427-8
Metadata
- Authors
- Gerwien, H., Hermann, S., Zhang, X., Korpos, E., Song, J., Kopka, K., Faust, A., Wenning, C., Gross, C. C., Honold, L., Melzer, N., Opdenakker, G., Wiendl, H., Schäfers, M., & Sorokin, L.
- Affiliations
- University of Münster (DE)
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, DE-48149 Münster, Germany.
- Rega Institute for Medical Research (BE)
- Corresponding author
- Gerwien, Hanna
- Hermann, Sven
- Kopka, Klaus
- Schäfers, Michael
- Sorokin, Lydia
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2016-11-09
- Volume
- 8
- Issue
- 364
- Pages
- 364ra152-364ra152
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W2553357145
- Cited by
- 113
- References
- 45
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 11 · 2023: 10 · 2022: 11 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 29 · 2017: 8 · 2016: 1
- FWCI
- 13.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- German Research Foundation
- Geconcerteerde Onderzoeksacties (GOA 2013/15)
- Charcot Foundation
- Fund for Scientific Research of Flanders
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- multiple sclerosis, MMP-9, MMP-2, experimental autoimmune encephalomyelitis, blood-brain barrier, leukocyte infiltration, matrix metalloproteinase inhibitors, positron emission tomography, molecular imaging, neuroinflammation, disease surveillance
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immune System, Inflammation, Leukocytes, Ligands, Magnetic Resonance Imaging, Male, Mice, Inbred C57BL, Mice, Transgenic, Multiple Sclerosis, Spinal Cord, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Matrix Metalloproteinases, Positron-Emission Tomography, Mice
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