Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis.
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.
MacKenzie-Graham
Allan
A
Laboratory of Neuro Imaging, Department of Neurology, University of California-Los Angeles, 635 Charles Young Drive South, Los Angeles, CA 90095-1769, USA.
Tinsley
Matthew R
MR
Shah
Kaanan P
KP
Aguilar
Cynthia
C
Strickland
Lauren V
LV
Boline
Jyl
J
Martin
Melanie
M
Morales
Laurie
L
Shattuck
David W
DW
Jacobs
Russell E
RE
Voskuhl
Rhonda R
RR
Toga
Arthur W
AW
D000818:Animals; D001284:Atrophy; D001931:Brain Mapping; D002525:Cerebellar Cortex / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000473:pathology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000276:immunology; D017711:Nonlinear Dynamics
D009185:Myelin Proteins