ABSENCE OF NEUROLOGICAL DEFICITS FOLLOWING EXTENSIVE DEMYELINATION INA CLASS I-DEFICIENT MURINE MODEL OF MULTIPLE-SCLEROSIS

Demyelination alone has been considered sufficient for development of neurological deficits following central nervous system (CNS) disease. However, extensive demyelination is not always associated with clinica l deficits in patients with multiple sclerosis (MS), the most common p rimary demyelinating disease in humans. We used the Theiler's murine e ncephalomyelitis virus model of demyelination to investigate the role of major histocompatibility complex (MHC) class I and class II gene pr oducts in the development of functional and neurophysiological deficit s following demyelination. We measured spontaneous clinical activity b y two independent assays and recorded hind-limb motor-evoked potential s in infected class I-deficient and class Il-deficient mice of an iden tical genetic background as well as in highly susceptible SJL/J mice. The results show that despite a similar distribution and extent of dem yelinated lesions in all mice, only class I-deficient mice were functi onally normal. We propose that the mechanism by which demyelinated cla ss I-deficient mice maintain neurologic function results from increase d sodium channel densities and the relative preservation of axons. The se findings are the first to implicate a role for MHC class I in the d evelopment of neurological deficits following demyelination.