Purkinje cell loss in experimental autoimmune encephalomyelitis

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.

Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair

“…As previously published, an increase in inflammatory CD45 + cell numbers into both white and grey matter of the CNS and a reduction in axon myelination in various brain regions is observed (Figure 4B–C) (Crawford et al, 2010a; Kumar et al, 2013; MacKenzie-Graham et al, 2009; Mangiardi et al, 2011; Moore et al, 2014b; Ziehn et al, 2010). For a detailed analysis of the CNS pathology please refer to the paper by Mangiardi et al, 2011.…”

In vivo magnetic resonance images reveal neuroanatomical sex differences through the application of voxel-based morphometry in C57BL/6 mice

“…A minimum deformation atlas (MDA) was created with the magnetic resonance images from all subjects (30 males and 30 females) used in this study as described (MacKenzie-Graham et al, 2009). The cortex and cerebellum were manually labelled on the MDA using BrainSuite 16a (Shattuck and Leahy, 2002) (http://brainsuite.org/) as described (MacKenzie-Graham et al, 2012).…”

Current Developments In Mri For Assessing Rodent Models of Multiple Sclerosis

“…High resolution T 2 WI has been shown to be useful for measurement of volumetric changes in EAE mouse brains that were significantly correlated with histopathological analysis [78]. This ex--vivo MRI study in EAE--mice found significant reductions in the volume of the cerebellum, cerebellar cortex and molecular layer of the cerebellar cortex.…”

“…In EAE mouse model, the loss of cortical volume was due to loss of Purkinje cells in the molecular cortex [32,78].…”

“…Atrophy in the molecular layer of the cerebellar cortex is related to loss of Purkinje cells [90]. Such detection of grey matter (GM) atrophy was important as it was strongly correlated with progressive development of clinical disability [78,91].…”