Effect of mast cell stabilization on experimental autoimmune encephalomyelitis development

Author(s)

Karen Henriette Pinke

• Document type: Doctoral Thesis
• Press: Botucatu. 2017-06-14.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2017-06-08
• Advisor: Alexandrina Sartori; Vanessa Soares Lara

Abstract

Multiple sclerosis is one of the most prevalent neurological human diseases. It triggers axonal damage and demyelinated areas in central nervous system (CNS) by an autoimmune response mediated by Th1, Th17 and T cytotoxic lymphocytes. Experimental autoimmune encephalomyelitis (EAE) is the most employed model of study this disease and mast cells appear to contribute to MS- and EAE- underlying immunopathogenesis. In this scenario, mast cell stabilizer drugs, such as ketotifen fumarate, could affect the development of these diseases by the blockage of exocytosis and degranulation. The aim of this study was to evaluate the effect of this drug on the development of EAE. For this, MOG/CFA-immunized female C57BL/6 mice were treated with ketotifen fumarate. The effect of treatment was determined by body weight loss and clinical score. Subsequently, EAE-associated histopathological and immunological parameters, as well as breakdown of blood-brain and blood-spinal cord barrier were analyzed. Comparisons about incidence values, daily and maximum clinical scores, and body weight loss revealed that ketotifen-treatment reduced the EAE-incidence and -severity. This protection was associated with the restoration of blood-spinal cord barrier function, absence or reduction of SNC lymphocytic infiltration and reduced microglial activation. Lower chymase-1, mMCP-4 and carboxypeptidase-1 gene expressions were also detected in the CNS, as well as higher activation of peripheral immune response in lymph node and splenic samples from immunized mice treated with ketotifen. Considering these results, it was concluded that the treatment with ketotifen fumarate prevents the clinical development of EAE by mechanisms related to maintenance of blood-spinal cord barrier function and consequent blockage of CNS inflammatory infiltrate. (AU)

• FAPESP's process: 14/00239-6 - Involvement of mast cells in the protective effect of vitamin D on experimental autoimmune encephalomyelitis
• Grantee: Karen Henriette Pinke
• Support Opportunities: Scholarships in Brazil - Doctorate