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In vivo and ex vivo assessment of the blood brain barrier integrity in different glioblastoma animal models

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Abstract

Blood brain barrier (BBB) disruption is used (pre)clinically as a measure for brain tumor malignancy and grading. During treatment it is one of the parameters followed rigorously to assess therapeutic efficacy. In animal models, both invasive and non-invasive methods are used to determine BBB disruption, among them Evans blue injection prior to sacrifice and T1-weighted magnetic resonance imaging (MRI) post contrast injection. In this study, we have assessed the BBB integrity with the methods mentioned above in two experimental high grade glioma models, namely the GL261 mouse glioblastoma model and the Hs683 human oligodendroglioma model. The GL261 model showed clear BBB integrity loss with both, contrast-enhanced (CE) MRI and Evans blue staining. In contrast, the Hs683 model only displayed BBB disruption with CE-MRI, which was not evident on Evans blue staining, indicating a limited BBB disruption. These results clearly indicate the importance of assessing the BBB integrity status using appropriate methods. Especially when using large therapeutic molecules that have difficulties crossing the BBB, care should be taken with the appropriate BBB disruption assessment studies.

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Acknowledgements

We would like to thank Prof. Van Gool and Prof. Kiss for supplying us with GL261 and Hs683 tumor cell lines. Furthermore, we would like to thank Prof. Lambrichts and Ms. Santermans for the use of the equipment of the lab of Histology at Hasselt University. Finally, we would also like to thank Prof Verfaillie for logistic support. We are grateful for the financial support from the European commission for EC-FP7 HEALTH.2011.2.2.1–2 (INMiND), from the Flemish government for FWO G0A7514 N, IWT-SBO MIRIAD (130065) and IWT-BRAINSTIM (060838) and from the University of Leuven for the program financing IMIR (PF 10/017).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Imaging and Pathology, Biomedical MRI, KU Leuven, O&N1, Herestraat 49, P.O. Box 505, 3000, Louvain, Belgium

    Cindy Leten, Tom Struys, Tom Dresselaers & Uwe Himmelreich

  2. Molecular Small Animal Imaging Center, KU Leuven, 3000, Louvain, Belgium

    Cindy Leten, Tom Dresselaers & Uwe Himmelreich

  3. Biomedical Research Institute Lab of Histology, University Hasselt, 3500, Hasselt, Belgium

    Tom Struys

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  1. Cindy Leten
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  2. Tom Struys
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  3. Tom Dresselaers
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  4. Uwe Himmelreich
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Correspondence to Uwe Himmelreich.

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Leten, C., Struys, T., Dresselaers, T. et al. In vivo and ex vivo assessment of the blood brain barrier integrity in different glioblastoma animal models. J Neurooncol 119, 297–306 (2014). https://doi.org/10.1007/s11060-014-1514-2

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  • DOI: https://doi.org/10.1007/s11060-014-1514-2

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