Year-end Sale % OFF 
Abstract
The blood–brain barrier (BBB) is necessary for maintaining brain homeostasis, but it also represents a major challenge for drug delivery to the brain tumors. A suitable in vivo Glioblastoma Multiforme (GBM) model is needed for efficient testing of BBB crossable pharmaceuticals. In this study, we firstly confirmed the BBB functionality in 3dpf zebrafish embryos by Lucifer Yellow, Evans Blue and DAPI microinjection. We then transplanted human GBM tumor cells into the zebrafish brain, in which implanted GBM cells (U87 and U251) were highly mitotic and invasive, mimicking their malignancy features in rodents’ brain. Interestingly, we found that, although extensive endothelial proliferation and vessel dilation were observed in GBM xenografts, the BBB was still not disturbed. Next, using the zebrafish orthotopic GBM xenograft model as an in vivo visual readout, we successfully identified a promising small compound named TNB, which could efficiently cross the zebrafish BBB and inhibit the progression of orthotopic GBM xenografts. These results indicate that TNB is a promising BBB crossable GBM drug worth to be further characterized in human BBB setting, also suggest the zebrafish orthotopic GBM model as an efficient visual readout for the BBB penetrating anti-GBM drugs.
Highlights
BBB is essential for maintaining brain homeostasis and protecting the brain from toxic substances[8,9]
With Glioblastoma Multiforme (GBM) micro-xenografts growing in the zebrafish brain, we found that the cerebral capillaries dilation and brain microvascular endothelial cells (BMECs) proliferation were intensive, the functionality of BBB in the GBM xenografts were generally not disturbed
At last, using this zebrafish orthotopic GBM model, we discovered one of our previously synthesized compounds—TNB, which could readily cross the zebrafish BBB and inhibit the growth of GBM xenografts in the brain
Summary
BBB is essential for maintaining brain homeostasis and protecting the brain from toxic substances[8,9]. Previous studies of the BBB development and maturation in zebrafish have shown that the zebrafish gradually develop a sophisticated BBB with tight-junction proteins and active transport systems, which is functionally and structurally similar to that of higher vertebrates These studies suggest that zebrafish could be applied as an experimental model organism for BBB-penetrating drug screening[11,12,13]. A particular advantage of the zebrafish xenograft model is that only a small number of cancer cells (50–500 cells per fish) are required for xenotransplantation All these results strongly indicate the embryo-larval zebrafish can be applied as an experimental tumor xenografted model for efficient BBB-penetrating drug identification[11].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
