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Int J Med Sci 2017; 14(13):1430-1435. doi:10.7150/ijms.22294 This issue Cite

Research Paper

ZW800-1 for Assessment of Blood-Brain Barrier Disruption in a Photothrombotic Stroke Model

Sungsu Lee^1*, Wonbong Lim^2*, Hye-Won Ryu³, Danbi Jo⁴, Jung-Joon Min⁵, Hyung-Seok Kim^3✉, Hoon Hyun^4✉

1. Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School, Gwangju 61469, South Korea;
2. Department of Premedical Program, School of Medicine, Chosun University, Gwangju 61452, South Korea;
3. Department of Forensic Medicine, Chonnam National University Medical School, Gwangju 61469, South Korea;
4. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, South Korea;
5. Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju 61469, South Korea.
* These authors contributed equally to this work.

✉ Corresponding authors: Hoon Hyun, Ph.D., 160 Baekseo-ro, Dong-gu, Gwangju 61469, South Korea Office: +82-61-379-2652; Fax: +82-61-379-8455 Email: hhyunac.kr Hyung-Seok Kim, M.D., Ph.D., 160 Baekseo-ro, Dong-gu, Gwangju 61469, South Korea Office: +82-62-220-4092; Fax: +82-62-223-4250 Email: veritasac.kr More

Abstract

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.

Keywords: ZW800-1, photothrombotic stroke model, blood-brain barrier, near-infrared fluorescence.

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