Liu, Xuguang; (1997) Monitoring chemically-induced myelin damages in the central nervous system via surface-recorded cerebellar auditory evoked potentials and radioimmunoassay of myelin basic protein in the cerebrospinal fluid. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This study aimed to evaluate two novel in vivo approaches to quantifying chemically-induced myelin damage in rats which might be useful for clinical monitoring of demyelination in humans. These were surface recording of the cerebellar auditory evoked potential (AEP), and radioimmunoassay of myelin basic protein (MBP) in the cerebrospinal fluid (CSF). The cerebellar AEP was characterized using a range of experimental manipulations, repeated CSF sampling techniques developed, and a radioimmunoassay shown to be practicable for detection of MBP in rat CSF. Two toxic models were established: lysolecithin (LPC) induced focal demyelination and triethyltin (TET) induced myelin oedema. The cerebellar AEP was recorded chronically via pre-implanted skull electrodes, and MBP concentration in the CSF was assayed in both models over the period of intoxication. Lesions were also characterized morphologically. Destruction of myelin by LPC produced a significant but transient decrease in AEP amplitude and rapid appearance of MBP in the CSF peaking at 24 hours. Myelin disruption without demyelination by TET intoxication produced a significant decrease in AEP amplitude at 24 hours, significant delay in latency, prolongation in conduction time and increase in the temperature dependence of conduction velocity at 72 hours, but no MBP was detected in the CSF. The surface-recorded cerebellar AEP was an effective indicator for monitoring progression of dysfunction associated with both LPC and TET induced lesions, although interpretation is complicated by interference from non-cerebellar components of the response. MBP was a sensitive and selective indicator which further distinguished myelin destruction from reversible myelin disruption. Both methods could therefore usefully be extended to clinical applications.

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