Ethidium Bromide Induced Demyelination of The Central Nervous System in A Dog Model of Secondary Progressive Multiple Sclerosis

Document Type : Original Article

Authors

1 Pathology department, Animal Health Research Institute, Dokki, Giza

2 Surgery Department, Faculty of Veterinary Medicine, Cairo University.

Abstract

Demyelinating lesions induced by intraspinal injection of gliotoxin have been studied for many years in order to gain insights into reasons for remyelination failure and in order to improve the understanding of the axonal conduction disorders in multiple sclerosis (MS). This work aimed to develop a model resembling clinical human-progressive MS where Ethidium bromide induced demyelination in dogs’ spinal cord is experimented. All animals received intraspinal injection of 20 μl of 0.1 % Ethidium bromide in the lateral columns using a microneedle syringe attached to a capillary tube. All animals were evaluated clinically with gait analysis, MRI imaging of the spinal cord and electron microscopic analysis. Results showed progressive clinical disability beginning from the third day post induction till 28 days; confirmed by the appearance of sclerotic plaques by MRI and hyperintense regions at the lateral columns of the spinal cord. The electron microscopic pictures showed progressive degenerative lesions characterized by death of oligodendrocytes and astrocytes leading to demyelination and vacuolation followed by axonal damage without signs of endogenous regeneration. Unique features were revealed compared to previous models; this dog model reached a more progressive form of MS where spontaneous remyelination was not observed till 28 days post induction. These findings support that dogs provide an alternative large model to study progressive MS.

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