Author(s): Kaji R, Suzumura A, Sumner AJ, Kaji R, Suzumura A, Sumner AJ
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Abstract To study the pathophysiology of immunologically mediated demyelination in the central nervous system (CNS), we injected 20 to 30 microliters of polyclonal antigalactocerebroside serum (AGC) into the lower thoracic dorsal column of the spinal cord in 20 Wistar rats. AGC-injected spinal cords contained areas of fascicular demyelination adjacent to the focus of axonal degeneration at the injection site. Somatosensory evoked potentials were recorded serially after tibial nerve stimulation. In 85\% of AGC-injected animals, the following characteristics were observed by 3 days after injection: (1) decreased amplitude of the cortically generated potential (P15); (2) failure of transmission of high-frequency (50 Hz) impulses (rate-dependent block); (3) delayed conduction velocity of the compound action potentials through the lesion. None of these changes was seen in 90\% of 20 rats injected with normal saline or control rabbit sera. In 7 rats with acrylamide-induced axonopathy or wallerian degeneration, the rate-dependent block was not observed. The onset of clinical symptoms (hindlimb ataxia) in AGC-injected rats was best correlated with development of the rate-dependent block. Clinical recovery was observed by 14 days after injection concurrent with restoration of P15 amplitude, when the rate-dependent block and decreased conduction velocities were unchanged. High-frequency-resistant conduction was re-established much later than clinical recovery in 3 rats. These findings suggest that failure of high-frequency impulse transmission may produce clinical symptoms and that a central adaptive mechanism to remodulated trains of impulses plays a role in clinical recovery from CNS demyelination.
This article was published in Brain
and referenced in Journal of Multiple Sclerosis
- Xuejun H Parsons
Direct conversion of pluripotent human embryonic stem cells into functional human neuronal or cardiomyocyte cell therapy derivatives for regenerative medicine