title: Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Laboratory of Neuro Imaging, Department of Neurology, University of California-Los Angeles, 635 Charles Young Drive South, Los Angeles, CA 90095-1769, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: MacKenzie-Graham
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Tinsley
authors.forename: Kaanan P
authors.initials: KP
authors.lastname: Shah
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aguilar
authors.forename: Lauren V
authors.initials: LV
authors.lastname: Strickland
authors.forename: Jyl
authors.initials: J
authors.lastname: Boline
authors.forename: Melanie
authors.initials: M
authors.lastname: Martin
authors.forename: Laurie
authors.initials: L
authors.lastname: Morales
authors.forename: David W
authors.initials: DW
authors.lastname: Shattuck
authors.forename: Russell E
authors.initials: RE
authors.lastname: Jacobs
authors.forename: Rhonda R
authors.initials: RR
authors.lastname: Voskuhl
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
mesh_terms: 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
chemical_list: D009185:Myelin Proteins