Acute hemorrhagic demyelination in a murine model of multiple sclerosis

Istvan Pirko¹ , Georgette L Suidan¹ , Moses Rodriguez² and Aaron J Johnson¹

¹Department of Neurology and Neuroscience, University of Cincinnati, Cincinnati, Ohio, USA

²Department of Neurology and Immunology, Mayo Clinic, Rochester, Minnesota, USA

author email corresponding author email

Journal of Neuroinflammation 2008, 5:31doi:10.1186/1742-2094-5-31


Published:	7 July 2008

Abstract

Acute hemorrhagic leukoencephalomyelitis (AHLE) is a rare neurological condition characterized by the development of acute hemorrhagic demyelination and high mortality. The pathomechanism of AHLE, as well as potential therapeutic approaches, have remained elusive due to the lack of suitable animal models. We report the first murine model of AHLE using a variation of the Theiler's Murine Encephalitis Virus (TMEV) MS model. During acute TMEV infection, C57BL/6 mice do not normally undergo demyelination. However, when 7 day TMEV infected C57BL/6 mice are intravenously administered the immunodominant CD8 T cell peptide, VP2_121–130, animals develop characteristics of human AHLE based on pathologic, MRI and clinical features including microhemorrhages, increased blood-brain barrier permeability, and demyelination. The animals also develop severe disability as assessed using the rotarod assay. This study demonstrates the development of hemorrhagic demyelination in TMEV infected C57BL/6 mice within 24 hours of inducing this condition through intravenous administration of CD8 T cell restricted peptide. This study is also the first demonstration of rapid demyelination in a TMEV resistant non-demyelinating strain without transgenic alterations or pharmacologically induced immunosuppression.