ZW800-1 for Assessment of Blood-Brain Barrier Disruption in a Photothrombotic Stroke Model
Open accessAbstract
Background: Since it is known that serum albumin-bound dyes can cross the blood-brain barrier (BBB) after ischemia, Evans Blue dye is commonly used to assess BBB disruption because of its rapid binding to serum albumin.In addition, indocyanine green (ICG), a clinically available dye, binds to serum proteins that could also be used for assessment of BBB impairment.Unlike these near-infrared (NIR) dyes, zwitterionic NIR fluorophore (ZW800-1) shows no serum binding, ultralow non-specific tissue uptake, and rapid elimination from the body via renal filtration.In this study, we report the use of ZW800-1 as a NIR fluorescence imaging agent for detecting BBB disruption in rat stroke models.Methods: Three types of NIR fluorophores, Evans Blue, ICG, and ZW800-1, were administered intraperitoneally into rat photothrombotic stroke models by using 4% concentration of each NIR dye.The NIR fluorescence signals in the infarcted brain tissue and biodistribution were observed in real-time using the Mini-FLARE ® imaging system up to 24 h post-injection.Results: ZW800-1 provided successful visualization of the ischemic injury site in the brain tissue, while the remaining injected dye was clearly excreted from the body within a certain period of time.Although Evans Blue and ICG provided mapping of the infarcted brain lesions, they exhibited high non-specific uptake in most of the tissues and organs and persisted in the body over 24 h post-injection.Conclusion: Our results suggest the promising application of ZW800-1 as a new strategy in BBB experiments and future therapeutic development.
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
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Synthesis and In Vivo Fate of Zwitterionic Near‐Infrared Fluorophores
Choi, H. S., Nasr, K., Alyabyev, S. B., Feith, D., Lee, J. H., Kim, S. H., Ashitate, Y., Hyun, H., Patonay, G., Strękowski, L., et al. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201102459 · Cited by 381 · see citing works
Self-citationSaunders, N. R., Dzięgielewska, K. M., Møllgård, K., & Habgood, M. D. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00385 · Cited by 308 · see citing works
Saunders, N. R., Dreifuss, J.-J., Dzięgielewska, K. M., Johansson, P. A., Habgood, M. D., MøllgÃ¥rd, K., & Bauer, H. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00404 · Cited by 261 · see citing works
Peripheral markers of blood–brain barrier damage
Marchi, N., Cavaglià, M., Fazio, V. J., Bhudia, S. K., Hallene, K. L., & Janigro, D. (2004) · Clinica Chimica Acta · doi:10.1016/j.cccn.2003.12.008 · Cited by 245 · see citing works
Wiessner, C., Bareyre, F. M., Allegrini, P. R., Mir, A. K., Frentzel, S., Zurini, M., Schnell, L., Oertle, T., & Schwab, M. E. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200302000-00003 · Cited by 209 · see citing works
Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging
Hyun, H., Park, M. H., Owens, E. A., Wada, H., Henary, M., Handgraaf, H. J. M., Vahrmeijer, A. L., Frangioni, J. V., & Choi, H. S. (2015) · Nature Medicine · doi:10.1038/nm.3728 · Cited by 196 · see citing works
Self-citationPhosphonated Near‐Infrared Fluorophores for Biomedical Imaging of Bone
Hyun, H., Wada, H., Bao, K., Gravier, J., Yadav, Y., Laramie, M., Henary, M., Frangioni, J. V., & Choi, H. S. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201404930 · Cited by 125 · see citing works
Self-citationCartilage‐Specific Near‐Infrared Fluorophores for Biomedical Imaging
Hyun, H., Owens, E. A., Wada, H., Levitz, A., Park, G., Park, M. H., Frangioni, J. V., Henary, M., & Choi, H. S. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201502287 · Cited by 115 · see citing works
Self-citationRecent advances in near-infrared fluorescence-guided imaging surgery using indocyanine green
Namikawa, T., Sato, T., & Hanazaki, K. (2015) · Surgery Today · doi:10.1007/s00595-015-1158-7 · Cited by 110 · see citing works
In vivo albumin labeling and lymphatic imaging
Wang, Y., Lang, L., Huang, P., Wang, Z., Jacobson, O., Kiesewetter, D. O., Ali, I., Teng, G., Niu, G., & Chen, X. S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414821112 · Cited by 100 · see citing works
Li, S., Johnson, J. S., Peck, A. S., & Xie, Q. R. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-016-1115-2 · Cited by 100 · see citing works
700-nm Zwitterionic Near-Infrared Fluorophores for Dual-Channel Image-Guided Surgery
Hyun, H., Henary, M., Gao, T., Narayana, L., Owens, E. A., Lee, J. H., Park, G., Wada, H., Ashitate, Y., Frangioni, J. V., et al. (2015) · Molecular Imaging and Biology · doi:10.1007/s11307-015-0870-4 · Cited by 79 · see citing works
Self-citationKlohs, J., Steinbrink, J. M., Bourayou, R., Mueller, S. G., Cordell, R., Licha, K., Schirner, M., Dirnagl, U., Lindauer, U., & Wunder, A. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.03.002 · Cited by 76 · see citing works
Quantitative imaging assessment of blood-brain barrier permeability in humans
Chassidim, Y., Veksler, R., Lublinsky, S., Pell, G. S., Friedman, A., & Shelef, I. (2013) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-10-9 · Cited by 76 · see citing works
Choi, K., Kim, H.-S., Park, M., Kim, J., Kim, J., Cho, K.-A., Lee, M. C., Lee, H.-J., & Cho, K. (2016) · Stroke · doi:10.1161/strokeaha.116.013205 · Cited by 73 · see citing works
Self-citationcGMP‐Compatible preparative scale synthesis of near‐infrared fluorophores
Hyun, H., Bordo, M. W., Nasr, K., Feith, D., Lee, J. H., Kim, S. H., Ashitate, Y., Moffitt, L. A., Rosenberg, M., Henary, M., et al. (2012) · Contrast Media & Molecular Imaging · doi:10.1002/cmmi.1484 · Cited by 67 · see citing works
Self-citationDynamic in vivo imaging of cerebral blood flow and blood–brain barrier permeability
Prager, O., Chassidim, Y., Klein, C., Levi, H., Shelef, I., & Friedman, A. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.08.009 · Cited by 65 · see citing works
Non-invasive visualization of CNS inflammation with nuclear and optical imaging
Wunder, A. P., Klohs, J., & Dirnagl, U. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.005 · Cited by 64 · see citing works
Near-Infrared Illumination of Native Tissues for Image-Guided Surgery
Owens, E. A., Hyun, H., Dost, T. L., Lee, J. H., Park, G., Pham, D.-H., Park, M. H., Choi, H. S., & Henary, M. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00038 · Cited by 62 · see citing works
Self-citationSynthesis and In Vivo Fate of Zwitterionic Near‐Infrared Fluorophores
Choi, H. S., Nasr, K., Alyabyev, S. B., Feith, D., Lee, J. H., Kim, S. H., Ashitate, Y., Hyun, H., Patonay, G., Strękowski, L., et al. (2011) · Angewandte Chemie · doi:10.1002/ange.201102459 · Cited by 50 · see citing works
Self-citationBartmann, H., Fuest, C., la Fougère, C. J., Xiong, G., Just, T., Schlichtiger, J., Winter, P., Böning, G., Wängler, B., Pekcec, A., et al. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02671.x · Cited by 46 · see citing works
COMBINATION OF TOLUIDINE DYE ISOMERS WITH PLASMA ALBUMIN
Allen, T. H., & Orahovats, P. D. (1950) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1950.161.3.473 · Cited by 45 · see citing works
Structure-Inherent Targeting of Near-Infrared Fluorophores for Image-Guided Surgery
Jo, D., & Hyun, H. (2017) · Chonnam Medical Journal · doi:10.4068/cmj.2017.53.2.95 · Cited by 43 · see citing works
Self-citationErgin, A., Wang, M., Zhang, J. Y., Bruce, J. N., Fine, R. L., Bigio, I. J., & Joshi, S. (2011) · Journal of Neuro-Oncology · doi:10.1007/s11060-011-0711-5 · Cited by 41 · see citing works
The Effects of Air Pollution on Ischemic Stroke Admission Rate
Alimohammadi, H., Fakhri, S., Derakhshanfar, H., Hosseini-Zijoud, S.-M., Safari, S., & Hatamabadi, H. (2016) · Chonnam Medical Journal · doi:10.4068/cmj.2016.52.1.53 · Cited by 31 · see citing works
Berezin, M. B. (2014) · Cited by 30 · see citing works
Phosphonated Near‐Infrared Fluorophores for Biomedical Imaging of Bone
Hyun, H., Wada, H., Bao, K., Gravier, J., Yadav, Y., Laramie, M., Henary, M., Frangioni, J. V., & Choi, H. S. (2014) · Angewandte Chemie · doi:10.1002/ange.201404930 · Cited by 28 · see citing works
Self-citationAnalyzing the blood–brain barrier: The benefits of medical imaging in research and clinical practice
Chassidim, Y., Vazana, U., Prager, O., Veksler, R., Bar‐Klein, G., Schoknecht, K., Fassler, M., Lublinsky, S., & Shelef, I. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.11.007 · Cited by 23 · see citing works
Real-timein vivoimaging of metastatic bone tumors with a targeted near-infrared fluorophore
Lim, W., Sohn, H., Ko, Y., Park, M., Kim, B., Jo, D., Jung, J. S., Yang, D. H., Kim, J., Kim, O. J., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20187 · Cited by 23 · see citing works
Self-citationCartilage‐Specific Near‐Infrared Fluorophores for Biomedical Imaging
Hyun, H., Owens, E. A., Wada, H., Levitz, A., Park, G., Park, M. H., Frangioni, J. V., Henary, M., & Choi, H. S. (2015) · Angewandte Chemie · doi:10.1002/ange.201502287 · Cited by 20 · see citing works
Self-citationCOMBINATION OF TOLUIDINE DYE ISOMERS WITH PLASMA ALBUMIN
Allen, T. H., & Orahovats, P. D. (1950) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1950.162.3.720-s · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Persistent luminescence nanoparticles for cancer theranostics application
Liu, N., Chen, X., Sun, X., Sun, X., & Shi, J. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00862-z · Cited by 97 · see citing works
Yan, B. C., Cao, J., Liu, J., Gu, Y., Xu, Z., Li, D., & Gao, L. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01312 · Cited by 75 · see citing works
Floc’h, J. L., Lu, H. D., Lim, T. L., Demore, C. E. M., Prud’homme, R. K., Hynynen, K., & Foster, F. S. (2019) · Molecular Imaging and Biology · doi:10.1007/s11307-019-01397-4 · Cited by 32 · see citing works
Bioluminescence and near-infrared fluorescence imaging for detection of metastatic bone tumors
Lim, W., Kim, B., Jo, G., Yang, D. H., Park, M. H., & Hyun, H. (2019) · Lasers in Medical Science · doi:10.1007/s10103-019-02801-9 · Cited by 18 · see citing works
Self-citationTumor-targeted near-infrared fluorophore for fluorescence-guided phototherapy
Park, M. H., Jo, G., Kim, E. J., Jung, J. S., & Hyun, H. (2020) · Chemical Communications · doi:10.1039/d0cc01366h · Cited by 17 · see citing works
Self-citationOrganic small-molecule NIR-II fluorophores for tumor phototheranostics
Xiang, D., Wang, Z., Zheng, H., Tang, Y., & Li, Q. (2026) · Light: Science & Applications · doi:10.1038/s41377-026-02212-w · Cited by 22 · see citing works
“13 Chemical structures of organic small-molecule metal complex BBB integrity evaluation, their limited albumin-binding speci fi city often leads to non-selective accumulation and signi fi cant adverse effects 203,204 .”
Sterically Shielded Hydrophilic Analogs of Indocyanine Green
Li, D., Gamage, R. S., & Smith, B. D. (2022) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.2c01229 · Cited by 14 · see citing works
Low-Dose Evans Blue Dye for Near-Infrared Fluorescence Imaging in Photothrombotic Stroke Model
Ryu, H.-W., Lim, W., Jo, D., Kim, S., Park, J., Min, J., Hyun, H., & Kim, H.-S. (2018) · International Journal of Medical Sciences · doi:10.7150/ijms.24257 · Cited by 14 · see citing works
Self-citationLi, J., Chen, Y., Peng, C., Hong, X., Liu, H., Fang, J., Zhuang, R., Pan, W., Zhang, D., Guo, Z., et al. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00177 · Cited by 13 · see citing works
Xu, J., Du, Y., Zhu, N., Li, J., Zhang, Y., Zhou, D., & Zhu, S. (2025) · Advanced Science · doi:10.1002/advs.202500443 · Cited by 10 · see citing works
Ador, T., Fournié, M., Rigollet, S., Counil, C., Stupar, V., Barbier, E., Pichon, C., & Delalande, A. (2025) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2025.02.016 · Cited by 9 · see citing works
Near-infrared fluorescent sorbitol probe for tumor diagnosis in vivo
Lee, S., Lim, W., Jo, D., Jung, J. S., Kim, S., Jo, G., Min, J., Choi, E. Y., & Hyun, H. (2018) · Journal of Industrial and Engineering Chemistry · doi:10.1016/j.jiec.2018.02.004 · Cited by 9 · see citing works
Self-citationPhotochemicallly Induced Thrombosis as a Model of Ischemic Stroke
Ostrova, I. V., Babkina, A. S., Lyubomudrov, M. A., Grechko, A. V., & Golubev, A. M. (2023) · General Reanimatology · doi:10.15360/1813-9779-2023-3-54-65 · Cited by 7 · see citing works
Liang, D., Tuo, X., Wang, Q., Zhao, L., Zhang, K., Wang, Y., Xue, F., Yin, P., Guo, L., Liu, Y., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.713583 · Cited by 5 · see citing works
Lysosome‐Targeted Bifunctional Therapeutics Induce Autodynamic Cancer Therapy
Raveendran, A., Ser, J., Park, S. H., Jang, P., Choi, H. S., & Cho, H. (2024) · Advanced Science · doi:10.1002/advs.202401424 · Cited by 5 · see citing works
Analysis of Convolutional Neural Network Segmentation Algorithm of Adenomyoma
Jin, Y., Huang, W., & Qu, Q. (2022) · Computational Intelligence and Neuroscience · doi:10.1155/2022/1629443 · Cited by 3 · see citing works
Human induced pluripotent cells in personalized treatment of monogenic epilepsies
Mohammadi, N. A., Freude, K., Haukedal, H., Tümer, Z., & Møller, R. S. (2020) · Journal of Translational Genetics and Genomics · doi:10.20517/jtgg.2020.29 · Cited by 3 · see citing works
Selective Deletion of NBCe1 in Reactive Astrocytes Attenuates Ischemic Stroke Brain Damage
Capuk, O., Berthold, E., Kaliyappan, K., Avunoori, M., Muduganti, R., Krishna, S., Metwally, S. A. H., McFarland, M., Song, S., Fiesler, V. M., et al. (2025) · Glia · doi:10.1002/glia.70075 · Cited by 2 · see citing works
Mouse Vocal Fold Permeability In Vivo: Effects of Novel Low‐Tech Injury and Instillation Methods
King, R. E., Ward-Shaw, E. T., & Lambert, P. F. (2025) · The Laryngoscope · doi:10.1002/lary.70266 · Cited by 1 · see citing works
Liang, D., Tuo, X., Zhao, L., Zhang, K., Wang, Y., Feng, X., Yin, P., Guo, L., Wei, J., Wang, Q., et al. (2020) · medRxiv · doi:10.1101/2020.02.23.20026948 · Cited by 1 · see citing works
Berdnikov, A. K., Сергеевич, А. А., Komleva, Y. K., Potapenko, I., & Salmina, A. B. (2026) · Annals of Clinical and Experimental Neurology · doi:10.17816/acen.1450
Li, M., Liang, D., Zhao, L., Wang, Y., He, X., Zhang, W., Wang, T., Bin, Y., Liu, Y., Ma, R., et al. (2026) · Technology in Cancer Research & Treatment · doi:10.1177/15330338261488986
- Authors
- Lee, S., Lim, W., Ryu, H.-W., Jo, D., Min, J.-J., Kim, H.-S., & Hyun, H.
- Affiliations
- Chonnam National University (KR)
- Chosun University (KR)
- Corresponding author
- Lee, Sungsu
- Lim, Wonbong
- Venue
- International Journal of Medical Sciences
- Publisher
- Ivyspring International Publisher
- Published
- 2017
- Volume
- 14
- Issue
- 13
- Pages
- 1430-1435
- ISSN
- 1449-1907 (ISSN-L)
- PMC
- PMC5707760
- OpenAlex
- W2770410786
- Cited by
- 22
- References
- 32
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 2
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- International Journal of Medical Sciences (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Ministry of Science, ICT and Future Planning (2015M3C1A3056410)
- National Research Foundation of Korea (NRF-2015R1C1A1A01053168, 2015M3C1A3056410, NRF-2017R1D1A1A02018640, 2017R1D1A1A02018640)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- blood-brain barrier disruption, photothrombotic stroke, Evans blue, indocyanine green, serum albumin binding, near-infrared fluorescence imaging, tissue distribution, renal excretion
- MeSH terms
- Quaternary Ammonium Compounds, Animals, Blood-Brain Barrier, Brain Ischemia, Evans Blue, Humans, Indocyanine Green, Spectrometry, Fluorescence, Sulfonic Acids, Spectroscopy, Near-Infrared, Stroke, 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
