Progressive model of multiple sclerosis following ethidium bromide injection in dogs' spinal cord: failure of endogenous remyelination

This paper evaluated the histopathological picture and pathological pathways of intoxication and apoptosis of oligodendrocytes and astrocytes, oligodendrocyte precursor cell migration and proliferation, and axonal viability of the dogs' model of Multiple Sclerosis (MS). Methodology/Principal Twenty-four dogs divided into 2 groups. All animals received intraspinal injection of 20 mu l of 0.1 % Ethidium bromide in the lateral columns using a micro needle syringe attached to a capillarytube. Spinal cord specimens of all animals were examined for routine histopathology, Toluidine blue semithin sections, Immunohistochemical analysis against Bax, Caspase 9, Myelin Basic Proteins, OLig2 and Glial fibrillary acidic proteins. Results showed marked differences in the Dogs' spinal cord damage and demyelination leading to a more progressive picture of MS model than small animals with high levels of apoptosis as observed by elevated Bax and Caspase 9 markers, a very high astrocytic reaction marked by GFAP and impaired proliferation and differentiation of Olig2 Oligodendrocyte precursor cells into mature oligodendrocytes with extensive axonal degeneration and vacuolation and remyelination was not observed until 28 days post induction. Conclusions/Significance: This model offers unique features, where a progressive form of demyelination and apoptosis and glial scar are different from those of other animal models and access to oligodendrocytes precursor cells was restricted and no spontaneous remyelination was observed. These finding support that dogs provides an alternative model studying progressive forms of MS and new treatment modalities.