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Demyelination Lesions Do Not Correlate with Clinical Manifestations by Bordetella pertussis Toxin Concentrations
Maiara Carolina Perussolo1, Bassam Felipe Mogharbel1, Claudia Sayuri Saçaki1
1Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Research Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Curitiba 80240-020, PR, Brazil.
Abstract:
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized as an inflammatory demyelinating disease. Given the need for improvements in MS treatment, many studies are mainly conducted through preclinical models such as experimental allergic encephalomyelitis (EAE). This study analyzes the relationships between histopathological and clinical score findings at EAE. Twenty-three female Rattus norvegicus Lewis rats from 6 to 8 weeks were induced to EAE. Nineteen rats underwent EAE induction distributed in six groups to establish the evolution of clinical signs, and four animals were in the control group. Bordetella pertussis toxin (PTX) doses were 200, 250, 300, 350 and 400 ng. The clinical scores of the animals were analyzed daily, from seven to 24 days after induction. The brains and spinal cords were collected for histopathological analyses. The results demonstrated that the dose of 250 ng of PTX induced a higher clinical score and reduction in weight. All induced groups demonstrated leukocyte infiltration, activation of microglia and astrocytes, and demyelinated plaques in the brains in histopathology. It was concluded that the dose of 250 ng and 350 ng of PTX were the best choices to trigger the brain and spinal cord demyelination lesions and did not correlate with clinical scores.
Insights
This study investigated experimental allergic encephalomyelitis (EAE) in rats, a model for multiple sclerosis. Researchers found specific doses of Bordetella pertussis toxin triggered demyelination but did not correlate with clinical scores.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) is an autoimmune central nervous system disease.
- Experimental allergic encephalomyelitis (EAE) is a key preclinical model for MS research.
- Understanding EAE histopathology and clinical correlations is crucial for MS treatment development.
Purpose of the Study:
- To analyze the relationship between histopathological findings and clinical scores in the EAE model.
- To determine optimal Bordetella pertussis toxin (PTX) doses for inducing EAE.
- To investigate demyelination and neuroinflammation in rat brains and spinal cords.
Main Methods:
- Induction of EAE in Lewis rats using varying doses of PTX (200-400 ng).
- Daily monitoring of clinical scores and animal weight for 24 days post-induction.
- Histopathological analysis of brain and spinal cord tissues for inflammation and demyelination.
Main Results:
- A PTX dose of 250 ng resulted in the highest clinical score and weight reduction.
- All EAE-induced rats showed leukocyte infiltration, activated microglia/astrocytes, and demyelinated plaques.
- Histopathology confirmed brain and spinal cord demyelination in induced groups.
Conclusions:
- Doses of 250 ng and 350 ng of PTX effectively induced brain and spinal cord demyelination in the EAE model.
- The induced demyelination lesions did not correlate with observed clinical scores.
- Further research is needed to reconcile clinical and pathological findings in EAE models.
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