Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis.
J Neuropathol Exp Neurol
; 64(1): 46-57, 2005 Jan.
Article
en En
| MEDLINE
| ID: mdl-15715084
For reasons that are not well understood, central nervous system repair in multiple sclerosis is often minimal. We present evidence, in a murine model of chronic progressive multiple sclerosis, that genetic factors can substantially influence remyelination, axonal integrity, and neurologic function. Four inbred mouse strains, SJL, B10.D1-H2(q), FVB, and SWR, developed extensive inflammatory demyelination by 3 months after infection with Theiler's murine encephalomyelitis virus. Demyelination continued lifelong in SJL and B10.D1-H2(q) mice, accompanied by axonal injury, minimal remyelination, and progressive motor dysfunction. In contrast, FVB and SWR mice showed less axonal injury, progressive remyelination, and stabilization of motor function. Genetic dominance of the reparative traits was demonstrated by crossing remyelinating strains (FVB and SWR) with nonremyelinating strains (SJL and B10.D1-H2(q)). All F1 mice developed a phenotype identical to FVB and SWR, showing extensive remyelination, partial preservation of axons, and preserved motor function. Analyses of viral RNA and antigen, immune cell infiltration, and antiviral antibody titers did not predict the phenotypic differences between strains. These results highlight the significant extent to which hereditary factors can control disease course and demonstrate that the switch from a pathogenic to a reparative phenotype can occur even after prolonged inflammatory demyelination.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Médula Espinal
/
Esclerosis Múltiple Crónica Progresiva
/
Genes Dominantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido