Modulation of the NALP3 Inflamassome in Microglia Cells Under Hipoxia in vitro.

• Grant number: 13/22974-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2014
• End date: December 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jean Pierre Schatzmann Peron
• Grantee: Juliana Pereira Zavatta
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 11/18703-2 - The role of Indoleamine-2,3-dioxigenase and the Triptophan - Kynurenines axis through NMDA receptors over the immune response in the EAE and stroke model, AP.JP

Abstract

Acute stroke strikes millions of people each year, and it is one of the most frequent cause of death and motor impairment in adults. With blood and oxygen deprivation in the CNS, neuronal death is widely found, being responsible for the impairment observed. Basically, post-ischemic inflammation follows two steps: i) secretion of pro-inflammatory factors by necrotic cells, and ii) recruitment of inflammatory cells from the immune system, such as neutrophils, macrophages and lymphocytes. Microglial cells activated may also secrete a large amount of cytokines, specially IL-1, IL-18 and IL-33. Such cytokines must be activated by active cleavage by a multiprotein complex called inflammasome. There are many different inflammasomes able to recognize both exogenous and endogenous danger signals, and the NALP3 is perhaps the most studied. Unfortunately, still little is known concerning the role of the inflammasomes in microglial cells, and yet its role during stroke. Moreover, activated microglial cells may also secrete large amounts of glutamate, inducing active neuronal death by excitotoxicity through NMDAR. Thus, in the present research, we aime to study whether glutamate secreted by microglial cells play any role in modulating the activity of NALP3 inflammasome in microglial cells after hipoxia in vitro.