A new class of central demyelinating lesion, and a new method of marking the sodium channel distribution along nerves, will be applied to a morphological and physiological examination of central neuropathy. Specifically, the project will examine the potential role of neuro-glial cells (astrocytes and oligodendrocytes) in influencing the physiological properties of pathological central nerve fibres. This role will be investigated by comparing the properties of fibers affected by one of five classes of demyelinating lesion. Each class of lesion will be characterised by a different type of glial presence: namely 1) a lesion of chroncially glial cell-free demyelinated nerve fibers (introduced in this application see figure 1); 2) a lesion of chronically glial cell-associated demyelinated nerve fibers (the central diphtheria toxin lesion); 3) a stable lesion free of glial cells to which glial cells are later introduced; 4) a stable lesion of glial-associated fibers from which glial cells are later removed; and 5) a lesion in which the demyelinated fibers undergo remyelination (the central lysolecithin lesion). These lesions will be examined both morphologically and electrophysiologically. Morphologically, the lesions will be examined to determine the sodium channel distribution along the demyelinated axolemma, and this distribution will be compared with that of the surrounding glial cells (when present). The sodium channels will be marked using a new technique introduced in this application (see figure 2). Physiologically, the different lesions will be examined for: 1) the presence or absence of conduction through the lesion; 2) the security of the conduction when present; and 3) the ability of the fibers to generate action potentials ectopically. These physiological properties are believed to determine both the presence or absence of negative symptoms such as paralysis and blindness, and the generation of positive symptoms such as paraesthesiae. By comparing the results obtained from study of the different lesions the potential effects of glial cells on demyelinated axons should be revealed, and their contribution to the symptomatology of demyelinating disease more clearly understood. In the lesion of multiple sclerosis for example, there is a marked variation in the degree of association of astrocytes to different demyelinated axons, and considering the properties of astrocytes it is pertinent to question if this variation may cause differences in the physiological properties of the axons. It is for example possible that the effectiveness of the astrocyte response may determine the presence or absence of remissions. Certainly, it is not unreasonable to hope that a greater understanding of the role of neuro-glial cells in pathological processes and repair may lead to new approaches in the symptomatic therapy of multiple sclerosis and related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021670-03
Application #
3403040
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1984-12-01
Project End
1988-02-29
Budget Start
1986-12-01
Budget End
1988-02-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Eastern Virginia Medical School
Department
Type
Schools of Medicine
DUNS #
City
Norfolk
State
VA
Country
United States
Zip Code
23501