article i nfo Article history: Accepted 10 July 2014 Available online xxxx 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 rela- tionship 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 usingin vivomagneticresonance 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 5 mm longi- tudinallyin three dimensionsin intact spinal cords revealing that 61% of theaxons 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 re- maining 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.
['Rory D. Spence', 'Florian Kurth', 'Noriko Itoh', 'Chandler R.L. Mongerson', 'Shannon H. Wailes', 'Mavis S. Peng', 'Allan MacKenzie-Graham']
Bringing CLARITY to gray matter atrophy