Abstract
Development of a novel, animal model for multiple sclerosis (MS) with reproducible and predictable lesion placement would enhance the discovery of effective treatments. Therefore, we would like to combine the advantages of the demyelination model with experimental autoimmune encephalomyelitis (EAE) to provide a local autoimmune encephalomyelitis (LAE) inside rat brain. We induced a demyelinating lesion by immunizing male Wistar rats, followed by blood-brain barrier opening protein (vascular endothelial growth factor) by stereotactic injection. We confirmed the immunization against myelin epitopes and minor neurological impairment. Histological assessment confirmed the lesion development after both 3- and 7 days post-injection. Our approach was sufficient to develop a demyelinating lesion with high reproducibility and low morbidity.
Highlights
Multiple sclerosis (MS) is an autoimmune demyelinating disease and is one of the most widespread neurological conditions, with more than 2 million people suffering worldwide [1]
This ineffectiveness is due in part to insufficient understanding of the pathomechanism of autoimmunity in the central nervous system (CNS) in MS patients
Serum antibody titer analysis, used for detection of antibodies against specific epitopes indicated that in all immunized groups, development of autoantibodies was robust (p < 0.0001) (Fig 1). This phenomenon was observed in case of, bovine spinal cord homogenate (Fig 1A), the immunogen, as well as MOG1-125 peptide (Fig 1B), confirming that the autoimmune response is robust against the myelin epitopes
Summary
Multiple sclerosis (MS) is an autoimmune demyelinating disease and is one of the most widespread neurological conditions, with more than 2 million people suffering worldwide [1]. Even though several therapeutics show efficacy in treatment of MS [2, 3], none of them are capable of curing the disease. This ineffectiveness is due in part to insufficient understanding of the pathomechanism of autoimmunity in the central nervous system (CNS) in MS patients. There is an urgent need to study the disease and test therapies in animal models. It is crucial to develop animal models that reflect the clinical complexity of the disease yet provide reproducibility of result and tools to reliably assess efficacy of tested therapies
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