TY - JOUR
T1 - Acute hemorrhagic demyelination in a murine model of multiple sclerosis
AU - Pirko, Istvan
AU - Suidan, Georgette L.
AU - Rodriguez, Moses
AU - Johnson, Aaron J.
N1 - Funding Information:
We would like to thank R. Scott Dunn and Ron Pratt for their technical assistance with MRI acquisition. We would also like to thank Hollis Miller for assistance in compliance issues and maintenance of our vertebrate studies. We would like to thank Mabel Pierce for the histologic preparations. This work was funded through a grant awarded by The Neuroscience Institute (TNI) of Cincinnati and the National Institutes of Health RO1 #NS058698.
PY - 2008/7/7
Y1 - 2008/7/7
N2 - 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, VP2121-130, 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.
AB - 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, VP2121-130, 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.
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U2 - 10.1186/1742-2094-5-31
DO - 10.1186/1742-2094-5-31
M3 - Article
C2 - 18606015
AN - SCOPUS:48249108717
SN - 1742-2094
VL - 5
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
M1 - 31
ER -