title: Global and 3D spatial assessment of neuroinflammation in rodent models of Multiple Sclerosis.
abstract: Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease. A technology for quantitative and 3 dimensional (3D) spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT). Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark ; Department of Experimental Medical Sciences, Immunology, University of Lund, Lund, Sweden ; Department of Veterinary Disease Biology, Biomedicine, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Shashank
authors.initials: S
authors.lastname: Gupta
authors.forename: Regine
authors.initials: R
authors.lastname: Utoft
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasseldam
authors.forename: Anja
authors.initials: A
authors.lastname: Schmidt-Christensen
authors.forename: Tine Dahlbaek
authors.initials: TD
authors.lastname: Hannibal
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Hansen
authors.forename: Nina
authors.initials: N
authors.lastname: Fransén-Pettersson
authors.forename: Noopur
authors.initials: N
authors.lastname: Agarwal-Gupta
authors.forename: Björn
authors.initials: B
authors.lastname: Rozell
authors.forename: Asa
authors.initials: A
authors.lastname: Andersson
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000276:immunology; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D041622:Tomography, Optical / Q000379:methods*