title: Bringing CLARITY to gray matter atrophy.
abstract: Gray matter atrophy has been shown to be a strong correlate to clinical disability in multiple sclerosis (MS) and its most commonly used animal model, experimental autoimmune encephalomyelitis (EAE). However, the relationship between gray mater atrophy and the spinal cord pathology often observed in EAE has never been established. Here EAE was induced in Thy1.1-YFP mice and their brains imaged using in vivo magnetic resonance imaging (MRI). The brains and spinal cords were subsequently optically cleared using Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY). Axons were followed 5mm longitudinally in three dimensions in intact spinal cords revealing that 61% of the axons exhibited a mean of 22 axonal ovoids and 8% of the axons terminating in axonal end bulbs. In the cerebral cortex, we observed a decrease in the mean number of layer V pyramidal neurons and a decrease in the mean length of the apical dendrites of the remaining neurons, compared to healthy controls. MRI analysis demonstrated decreased cortical volumes in EAE. Cross-modality correlations revealed a direct relationship between cortical volume loss and axonal end bulb number in the spinal cord, but not ovoid number. This is the first report of the use of CLARITY in an animal model of disease and the first report of the use of both CLARITY and MRI.
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Rory D
authors.initials: RD
authors.lastname: Spence
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Kurth
authors.affiliation: Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Itoh
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Chandler R L
authors.initials: CR
authors.lastname: Mongerson
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Shannon H
authors.initials: SH
authors.lastname: Wailes
authors.affiliation: Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Mavis S
authors.initials: MS
authors.lastname: Peng
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: amg@ucla.edu.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: MacKenzie-Graham
mesh_terms: D020106:Acrylamide; D000818:Animals; D001284:Atrophy / Q000473:pathology; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D066128:Gray Matter / Q000166:cytology / Q000473:pathology*; D020100:Hydrogels; D047569:Laser Scanning Cytometry / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064847:Multimodal Imaging; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology*
chemical_list: D020100:Hydrogels; D020106:Acrylamide