Brain Advance Access originally published online on September 8, 2005
Brain 2005 128(11):2713-2721; doi:10.1093/brain/awh626
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Demyelinated neocortical lesions in marmoset autoimmune encephalomyelitis mimic those in multiple sclerosis
1 Department of Clinical Neurology, University of Oxford, Oxford, UK and 2 Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, MD, USA
Correspondence to: Dr I. Pomeroy, Department of Neuropathology, Radcliffe Infirmary, Oxford, OX2 6HE, UK E-mail: ian.pomeroy{at}clneuro.ox.ac.uk
The use of immunohistochemical methods has led to a new understanding of the prevalence and significance of cortical lesions in multiple sclerosis but these lesions have not yet been formally described in an animal model. In this study we have set out to use immunohistochemical techniques to identify and describe cortical lesions in marmosets with experimental autoimmune encephalomyelitis (EAE). Using antibodies to proteolipid protein (PLP), we found a total of 70 cortical lesions in 11 tissue blocks from 6 animals. These lesions were subdivided into leucocortical (40), intracortical (12) and subpial lesions (18). We quantified the density of inflammatory cells within lesions using a double labelling protocol which employed anti-PLP in addition to antibodies against markers of B-lymphocytes (CD20), T-lymphocytes (CD3), macrophages (MAC387) and MHC-II expressing cells (CR3/43). This analysis revealed that the large subpial lesions accounted for the majority of demyelinated cortex (88%) despite possessing the lowest density of inflammatory cells. This study has shown that lesions in this model share many of the major features of cortical lesions in multiple sclerosis both in terms of morphology and inflammatory cell content. We believe that this tool can be exploited in future studies to investigate the aetiology, development and clinical significance of cortical lesions in demyelinating disease.
Key Words: multiple sclerosis; cortex; inflammation; experimental autoimmune encephalomyelitis; marmoset; Callithrix jacchus; immunohistochemistry; demyelination; myelin oligodendrocyte glycoprotein
Abbreviations: EAE = experimental autoimmune encephalomyelitis; LFB = luxol fast blue; NAGM = normal appearing grey matter; PLP = proteolipid protein
Received May 5, 2005. Revised June 24, 2005. Accepted August 1, 2005.
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