Estudo do papel do fator ativador plaquetário na encefalomielite autoimune experimental

• Ano de defesa: 2010
• Autor(a) principal: David Henrique Rodrigues
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais
• Palavras-chave em Português: Biologia celular; Células Inflamação; Fator ativador de plaquetas; Esclerose multipla; Sistema nervoso Inflamação; Encefalomielite auto-imune experimental
• Link de acesso: https://hdl.handle.net/1843/BUOS-8M6KF5

Multiple sclerosis (MS) is a disease that causes myelin destruction in the central nervous system (CNS) neurons. It affects young adults and leads to motor dysfunctions, like front and hind limbs paralysis and sensitive dysfunctions. The pathophysiological and ethiopatogenic me-chanisms are still not well understood and available treatments do not alter prognosis significant-ly. The experimental autoimmune encephalomyelitis (EAE) is one of the animal models used for the study of the disease, due to its similarity with MS. In this context, inflammatory mediators like platelet activating factor (PAF), could have an essential role in the establishment of the neu-roinflammatory condition. Thus, the objective of this study was to investigate the role of inflammatory mediators, especially PAF, in EAE. It was evaluated the rolling and adhesion of leukocytes in mice deficient for the receptor of PAF (PAFR-/-) induced with EAE, as well as clinical, behavioural, histologic and molecular parameters in these mice. PAFR-/- animals develop a milder EAE when compared to wild type (WT) mice. Histopa-thologic analyses revealed fewer inflammatory infiltrates in PAFR-/- animals and the presence of polimorphonuclear leukocytes in these animals, contrasting with WT animals that presented an inflammatory infiltrate composed predominantly of mononuclear cells. Levels of proinflammato-ry molecules in the CNS of PAFR-/- animals were also lower than WT animals, indicating a dimi-nishment in the stimuli to the migration of mononuclear cells in these animals. However, adhe-sion and rolling of cells in brain microvasculature, which constitute essential steps in cellular migration, were similar in PAFR-/- animals when compared to WT. Absence of CD4+ cells and IL-17 producer cells in PAFR-/- animals confirmed the deficiency in proinflammatory parameters in these mice. In parallel, behavioural parameters were investigated in EAE-induced animals. Nonethe-less, no significant changes were found in memory and anxiety in mice with EAE either before the onset of clinical signs or after EAE remission. In conclusion, this study demonstrated that PAF exerts a fundamental role in the neuroin-flammatory process during EAE, probably related to the types of cells that invade the CNS.