Fricke Inga B, Schelhaas Sonja, Zinnhardt Bastian, Viel Thomas, Hermann Sven, Couillard-Després Sébastien, Jacobs Andreas H
European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.
Imaging Neuroinflammation in Neurodegenerative Diseases (INMiND) EU FP7 Consortium, Münster, Germany.
Eur J Neurosci. 2017 Apr;45(7):975-986. doi: 10.1111/ejn.13540. Epub 2017 Mar 7.
Bioluminescence imaging in transgenic mice expressing firefly luciferase in Doublecortin (Dcx) neuroblasts might serve as a powerful tool to study the role of neurogenesis in models of brain injury and neurodegeneration using non-invasive, longitudinal in vivo imaging. Therefore, we aimed to use BLI in B6(Cg)-Tyrc-2J/J Dcx-Luc (Doublecortin-Luciferase, Dcx-Luc) mice to investigate its suitability to assess neurogenesis in a unilateral injection model of Parkinson's disease. We further aimed to assess the blood brain barrier leakage associated with the intranigral 6-OHDA injection to evaluate its impact on substrate delivery and bioluminescence signal intensity. Two weeks after lesion, we observed an increase in bioluminescence signal in the ipsilateral hippocampal region in both, 6-OHDA and vehicle injected Dcx-Luc mice. At the same time, no corresponding increase in Dcx neuroblast numbers could be observed in the dentate gyrus of C57Bl6 mice. Blood brain barrier leakage was observed in the hippocampal region and in the degenerating substantia nigra of C57Bl6 mice in vivo using T1 weighted Magnetic Resonance Imaging with Gadovist and ex vivo using Evans Blue Fluorescence Reflectance Imaging and mouse Immunoglobulin G staining. Our data suggests a BLI signal dependency on blood brain barrier permeability, underlining a major pitfall of substrate/tracer dependent imaging in invasive disease models.
在双皮质素（Dcx）神经母细胞中表达萤火虫荧光素酶的转基因小鼠中的生物发光成像，可能成为一种强大的工具，用于使用非侵入性的纵向体内成像来研究神经发生在脑损伤和神经退行性变模型中的作用。因此，我们旨在利用B6（Cg）-Tyrc-2J/J Dcx-Luc（双皮质素-荧光素酶，Dcx-Luc）小鼠中的生物发光成像来研究其在帕金森病单侧注射模型中评估神经发生的适用性。我们还旨在评估与黑质内注射6-羟基多巴胺相关的血脑屏障渗漏情况，以评估其对底物递送和生物发光信号强度的影响。损伤两周后，我们在注射6-羟基多巴胺和注射赋形剂的Dcx-Luc小鼠的同侧海马区均观察到生物发光信号增加。与此同时，在C57Bl6小鼠的齿状回中未观察到Dcx神经母细胞数量相应增加。使用钆塞酸二钠的T1加权磁共振成像在体内以及使用伊文思蓝荧光反射成像和小鼠免疫球蛋白G染色在体外观察到C57Bl6小鼠海马区和退化的黑质中有血脑屏障渗漏。我们的数据表明生物发光信号依赖于血脑屏障通透性，这突出了在侵袭性疾病模型中依赖底物/示踪剂成像的一个主要缺陷。
