Date of Award

Spring 1990

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Program/Concentration

Biomedical Sciences -- Neuroscience

Committee Director

Kenneth J. Smith

Committee Member

George E. Goode

Committee Member

Francis J. Liuzzi

Committee Member

Keith A. Carson

Abstract

Multiple sclerosis causes demyelination of central nerve fibers, and it is this pathology which results in most of the symptoms of the disease. The repair of the fibers by remyelination has been advanced as a potential symptomatic therapy, but at present the conduction properties of remyelinated central fibers are not well understood. In this study the conduction properties of Schwannian or oligodendrocyte remyelinated central nerve fibers have been determined. In addition, the status of the blood-brain barrier has been examined in lesions characterized by Schwann cell remyelination. These lesions chronically lack astrocytes, a cell believed to be involved in the induction of barrier properties.

Large focal demyelinating and remyelinating lesions were induced in the rat dorsal column by the intraspinal injection of ethidium bromide, either alone or in conjunction with 40Gy of beta irradiation. The electrophysiological properties of the lesion were correlated with its morphological appearance at different stages of lesion development, using both acutely prepared animals, and animals with chronically implanted stimulating and recording electrodes. Blood-brain barrier function was assessed by injecting horseradish peroxidase (HRP) intravenously and examining the lesion for extravasated HRP. During the period of demyelination the conducting fibers showed prolonged refractory periods of transmission (RPT) and an inability to conduct trains of impulses at high frequency, although conduction in most fibers was blocked. Conduction was restored to some demyelinated fibers by a reduction in body temperature, but not by the administration of potassium channel blocking agents. Remyelination by either Schwann cells or oligodendrocytes was accompanied by the restoration of near normal conduction properties in virtually all of the affected fibers, as measured by the RPT, and the ability of the fibers to conduct trains of impulses at physiological frequencies. The blood-brain barrier was disrupted during the period of demyelination, and was not reformed even after the complete remyelination of the lesion by Schwann cells.

We conclude (1) that the induction of remyelination of central demyelinated nerve fibers by either Schwann cells or by oligodendrocytes should be effective in promoting the restoration of normal function, and (2) that Schwann cells are not effective in inducing the reformation of an intact blood brain barrier.

DOI

10.25777/5swx-p103

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