Investigação do recrutamento celular em camundongos selvagens eTNFR1-/- no modelo experimental de encefalite herpética grave

• Ano de defesa: 2008
• Autor(a) principal: Marcia de Carvalho Vilela
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Encefalite; Neuroinflamação; Herpes simplex vírus tipo 1; TNFR1; Microscopia; Herpesvírus humano 1; Patologia; Receptores de fatores de necrose tumoral; Camundongos
• Link de acesso: http://hdl.handle.net/1843/ECJS-7K7NZ3

The Herpes Simplex Virus-1 (HSV-1) is a human pathogen that causes severe encephalitis. The development of experimental models of HSV-1 encephalitis (HSE) is relevant for the comprehension of this potential lethal condition. C57BL/6 (wt) mice were inoculated intracerebrally with 104 PFU of neurotropic HSV-1. All animals developed signs of HSE anddied until 6 days post infection (dpi). Intravital microscopy revealed an increased leukocyte rolling and adhesion in the brain microvasculature of infected wt mice at 1, 3 and 5 dpi. Fragments of the brain were removed to evaluate cerebral levels of chemokines and viral particles, and histopathological alterations. There was an increase in the levels of thechemokines MCP-1/CCL2, MIP-1/CCL3, RANTES/CCL5, Kc/CXCL1 and MIG/CXCL9 in the brain tissue of HSV-1 infected mice. High viral load was found in the central nervous system (CNS) of infected mice with 1 and 3 dpi. Histological analysis demonstrated diffuse meningitis and focal encephalitis characterized by mononuclear cell infiltrates in infected wtmice. A model of severe herpetic encephalitis in C57BL/6 mice was established. When TNFR1 -/- mice were infected with HSV-1, there was no significant difference in the survival curve and the virus load in CNS when compared with infected wt mice. Accordingly, there were increased rolling and adhesion of leukocytes along the brain endothelium wall and high levels of chemokines in the CNS of infected TNFR1 -/- mice but with no difference when comparing with infected wt mice. Therefore the receptor 1 for TNF-a may not play a relevant role in this model of severe herpetic encephalitis