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Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis

MacKenzie-Graham, Allan and Tinsley, Matthew R. and Shah, Kaanan P. and Aguilar, Cynthia and Strickland, Lauren V. and Boline, Jyl and Martin, Melanie and Morales, Laurie and Shattuck, David W. and Jacobs, Russell E. and Voskuhl, Rhonda R. and Toga, Arthur W. (2006) Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis. NeuroImage, 32 (3). pp. 1016-1023. ISSN 1053-8119. doi:10.1016/j.neuroimage.2006.05.006.

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Brain atrophy measured by MRI is an important correlate with clinical disability and disease duration in multiple sclerosis (MS). Unfortunately, neuropathologic mechanisms which lead to this grey matter atrophy remain unknown. The objective of this study was to determine whether brain atrophy occurs in the mouse model, experimental autoimmune encephalomyelitis (EAE). Postmortem high-resolution T2-weighted magnetic resonance microscopy (MRM) images from 32 mouse brains (21 EAE and 11 control) were collected. A minimum deformation atlas was constructed and a deformable atlas approach was used to quantify volumetric changes in neuroanatomical structures. A significant decrease in the mean cerebellar cortex volume in mice with late EAE (48–56 days after disease induction) as compared to normal strain, gender, and age-matched controls was observed. There was a direct correlation between cerebellar cortical atrophy and disease duration. At an early time point in disease, 15 days after disease induction, cerebellar white matter lesions were detected by both histology and MRM. These data demonstrate that myelin-specific autoimmune responses can lead to grey matter atrophy in an otherwise normal CNS. The model described herein can now be used to investigate neuropathologic mechanisms that lead to the development of gray matter atrophy in this setting.

Item Type:Article
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Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2006 Elsevier Inc. Received 13 February 2006; revised 19 April 2006; accepted 2 May 2006. Available online 27 June 2006. This work was generously supported by a research grant from NCRR U24 RR021760 (AWT), NIH U54 RR 021813 (AWT), NIH P41 013642 (AWT), NMSS CA 1028 (RRV), NMSS RG 3593 (RRV), and NMSS PP 1098 (RRV). The authors wish to acknowledge their deep appreciation to the members of the Laboratory of Neuro Imaging (LONI) and the Mouse Biomedical Informatics Research Network (Mouse BIRN), without whom this research would not have been possible. We also acknowledge Dr. Robert Elashoff for assistance with statistical analyses and Dr. Nancy Sicotte for collaborative discussions.
Funding AgencyGrant Number
NIHU24 RR021760
NIHU54 RR 021813
NIHP41 013642
National Multiple Sclerosis SocietyCA 1028
National Multiple Sclerosis SocietyRG 3593
National Multiple Sclerosis SocietyPP 1098
Issue or Number:3
Record Number:CaltechAUTHORS:20160127-155032352
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Official Citation:Allan MacKenzie-Graham, Matthew R. Tinsley, Kaanan P. Shah, Cynthia Aguilar, Lauren V. Strickland, Jyl Boline, Melanie Martin, Laurie Morales, David W. Shattuck, Russell E. Jacobs, Rhonda R. Voskuhl, Arthur W. Toga, Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis, NeuroImage, Volume 32, Issue 3, September 2006, Pages 1016-1023, ISSN 1053-8119, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64035
Deposited By: Ruth Sustaita
Deposited On:28 Jan 2016 23:20
Last Modified:10 Nov 2021 23:24

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