Purkinje cell loss in experimental autoimmune encephalomyelitis

被引:56
|
作者
MacKenzie-Graham, Allan [1 ]
Tiwari-Woodruff, Seema K. [2 ]
Sharma, Gaurav [2 ]
Aguilar, Cynthia [1 ]
Vo, Kieumai T. [1 ]
Strickland, Lauren V. [1 ]
Morales, Laurie [2 ]
Fubara, Boma [3 ]
Martin, Melanie [4 ]
Jacobs, Russell E. [5 ]
Johnson, G. Allan [3 ]
Toga, Arthur W. [1 ]
Voskuhl, Rhonda R. [2 ]
机构
[1] Lab Neuro Imaging, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Neurol, Multiple Sclerosis Program, Los Angeles, CA USA
[3] Duke Univ, Ctr Vivo Microscopy, Durham, NC 27706 USA
[4] Univ Winnipeg, Dept Phys, Winnipeg, MB R3B 2E9, Canada
[5] CALTECH, Beckman Inst, Pasadena, CA 91125 USA
关键词
Cerebellum; Gray matter atrophy; Mouse; MRI; Multiple sclerosis; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; PROGRESSIVE MULTIPLE-SCLEROSIS; AUTOMATED IMAGE REGISTRATION; CHRONIC-RELAPSING EAE; NA-V; 1.8; BRAIN ATROPHY; SPINAL-CORD; LESION LOCALIZATION; SODIUM-CHANNELS; UP-REGULATION;
D O I
10.1016/j.neuroimage.2009.06.073
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. Published by Elsevier Inc.
引用
收藏
页码:637 / 651
页数:15
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