Article

Purkinje cell loss in experimental autoimmune encephalomyelitis.

Laboratory of Neuro Imaging, Suite 225, Los Angeles, CA 90095-1769, USA.
NeuroImage (impact factor: 5.89). 08/2009; 48(4):637-51. DOI:10.1016/j.neuroimage.2009.06.073 pp.637-51
Source: PubMed

ABSTRACT 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.

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Keywords

Anatomical delineations
 
cerebellar cortex
 
clinical disability
 
Cross modality
 
disease duration
 
EAE mice
 
experimental autoimmune encephalomyelitis
 
gray matter atrophy
 
multiple sclerosis
 
neurodegenerative disease
 
neuropathology approaches
 
population atlasing
 
post-mortem high-resolution T2-weighted magnetic resonance microscopy
 
pro-apoptotic marker caspase-3
 
Purkinje cell loss
 
Purkinje cell number
 
significant association
 
significant decrease
 
stained magnetic resonance histology images
 
underlying neuropathology