title: In vivo bioluminescence imaging of neurogenesis - the role of the blood brain barrier in an experimental model of Parkinson's disease.
abstract: 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.
authors.affiliation: 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.
authors.forename: Inga B
authors.initials: IB
authors.lastname: Fricke
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Schelhaas
authors.affiliation: 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.
authors.forename: Bastian
authors.initials: B
authors.lastname: Zinnhardt
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: Imaging Neuroinflammation in Neurodegenerative Diseases (INMiND) EU FP7 Consortium, Münster, Germany.|Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.|Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Couillard-Després
authors.affiliation: 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.|Department of Geriatrics and Neurology, Johanniter Hospital, Bonn, Germany.
authors.forename: Andreas H
authors.identifier: 0000-0003-2929-8042
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism*; D002199:Capillary Permeability; D018891:Dentate Gyrus / Q000000981:diagnostic imaging; D038524:Diffusion Magnetic Resonance Imaging; D000089662:Doublecortin Protein; D005070:Evans Blue / Q000493:pharmacokinetics; D049449:Luminescence; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D061848:Optical Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000209:etiology; D013378:Substantia Nigra / Q000000981:diagnostic imaging
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D009942:Organometallic Compounds; C090600:gadobutrol; D005070:Evans Blue; D016627:Oxidopamine
keywords: Doublecortin; magnetic resonance; neurodegeneration; optical imaging; substrate delivery