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Purkinje cell loss in experimental autoimmune encephalomyelitis

MacKenzie-Graham, Allan and Tiwari-Woodruff, Seema K. and Sharma, Gaurav and Aguilar, Cynthia and Vo, Kieumai T. and Strickland, Lauren V. and Morales, Laurie and Fubara, Boma and Martin, Melanie and Jacobs, Russell E. and Johnson, G. Allan and Toga, Arthur W. and Voskuhl, Rhonda R. (2009) Purkinje cell loss in experimental autoimmune encephalomyelitis. NeuroImage, 48 (4). pp. 637-651. ISSN 1053-8119.

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Gray matter atrophy observed by brain MRI is an important correlate to clinical disability and disease duration in multiple sclerosis. The objective of this study was to link brain atrophy visualized by neuroimaging to its underlying neuropathology using the MS model, experimental autoimmune encephalomyelitis (EAE). Volumetric changes in brains of EAE mice, as well as matched healthy normal controls, were quantified by collecting post-mortem high-resolution T2-weighted magnetic resonance microscopy and actively stained magnetic resonance histology images. Anatomical delineations demonstrated a significant decrease in the volume of the whole cerebellum, cerebellar cortex, and molecular layer of the cerebellar cortex in EAE as compared to normal controls. The pro-apoptotic marker caspase-3 was detected in Purkinje cells and a significant decrease in Purkinje cell number was found in EAE. Cross modality and temporal correlations revealed a significant association between Purkinje cell loss on neuropathology and atrophy of the molecular layer of the cerebellar cortex by neuroimaging. These results demonstrate the power of using combined population atlasing and neuropathology approaches to discern novel insights underlying gray matter atrophy in animal models of neurodegenerative disease.

Item Type:Article
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URLURL TypeDescription CentralArticle
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2010 Elsevier B.V. Received 31 March 2009; revised 20 June 2009; accepted 29 June 2009. Available online 6 July 2009. This work was generously supported by a research grant from NMSS FG 1759A1/1 (AMG), NCRR U24 RR021760 (AWT), NIH U54 RR 021813 (AWT), NMSS CA 1028 (RRV), NMSS RG 3593 (RRV), NMSS PP 1098 (RRV), NIH P41 05959 (GAJ), and NIH R24 CA092656 (GAJ). 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). We would also like to acknowledge the late Michael D. Fehnel, who made this work possible.
Funding AgencyGrant Number
National Multiple Sclerosis SocietyFG 1759A1/1
National Multiple Sclerosis SocietyCA 1028
National Multiple Sclerosis SocietyRG 3593
National Multiple Sclerosis SocietyPP 1098
National Center for Research Resources (NCRR)U24 RR021760
NIHU54 RR 021813
NIHP41 05959
NIHR24 CA092656
Subject Keywords:Cerebellum; Gray matter atrophy; Mouse; MRI; Multiple sclerosis
Issue or Number:4
Record Number:CaltechAUTHORS:20100308-110526990
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Official Citation:Allan MacKenzie-Graham, Seema K. Tiwari-Woodruff, Gaurav Sharma, Cynthia Aguilar, Kieumai T. Vo, Lauren V. Strickland, Laurie Morales, Boma Fubara, Melanie Martin, Russell E. Jacobs, G. Allan Johnson, Arthur W. Toga, Rhonda R. Voskuhl, Purkinje cell loss in experimental autoimmune encephalomyelitis, NeuroImage, Volume 48, Issue 4, December 2009, Pages 637-651, ISSN 1053-8119, DOI: 10.1016/j.neuroimage.2009.06.073.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17691
Deposited By: Tony Diaz
Deposited On:12 Mar 2010 22:56
Last Modified:03 Oct 2019 01:31

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