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In vivo bioluminescence imaging of neurogenesis – the role of the blood brain barrier in an experimental model of Parkinson's disease
Author(s) -
Fricke Inga B.,
Schelhaas Sonja,
Zinnhardt Bastian,
Viel Thomas,
Hermann Sven,
CouillardDesprés Sébastien,
Jacobs Andreas H.
Publication year - 2017
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13540
Subject(s) - doublecortin , neurogenesis , dentate gyrus , bioluminescence imaging , neuroscience , substantia nigra , blood–brain barrier , parkinson's disease , bioluminescence , ex vivo , hippocampal formation , pathology , luciferase , in vivo , biology , medicine , central nervous system , biochemistry , transfection , microbiology and biotechnology , disease , gene
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.