In vivo and ex vivo assessment of the blood brain barrier integrity in different glioblastoma animal models
In vivo and ex vivo assessment of the blood brain barrier integrity in different glioblastoma animal models
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DOI：
10.1007/s11060-014-1514-2
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发表时间：
2014-09-01
影响因子：
3.9
通讯作者：
Himmelreich, Uwe
中科院分区：
文献类型：
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作者：
Leten, Cindy;Struys, Tom;Himmelreich, Uwe
血脑屏障 (BBB) 破坏在临床前（前）用作脑肿瘤恶性程度和分级的衡量标准。在治疗过程中，它是评估治疗效果时严格遵循的参数之一。在动物模型中，使用侵入性和非侵入性方法来确定 BBB 破坏，其中包括处死前注射伊文思蓝和注射对比剂后 T1 加权磁共振成像 (MRI)。在本研究中，我们利用上述方法在两个实验性高级别胶质瘤模型（即GL261小鼠胶质母细胞瘤模型和Hs683人少突胶质细胞瘤模型）中评估了BBB完整性。 GL261 模型通过对比增强 (CE) MRI 和伊文思蓝染色显示明显的血脑屏障完整性丧失。相比之下，Hs683模型仅通过CE-MRI显示BBB破坏，这在伊文思蓝染色中并不明显，表明BBB破坏有限。这些结果清楚地表明了使用适当方法评估 BBB 完整性状态的重要性。特别是当使用难以穿过 BBB 的大治疗分子时，应注意适当的 BBB 破坏评估研究。
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.