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POLARIZATION OF MICROGLIA AND ITS THERAPEUTIC POTENTIAL IN SEPSIS
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro (UNIRIO). Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro (UNIRIO). Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.
Abstract
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to
infection, leaving the inflammation process without a proper resolution, leading to tissue damage
and possibly sequelae. The central nervous system (CNS) is one of the first regions affected by the
peripheral inflammation caused by sepsis, exposing the neurons to an environment of oxidative
stress, triggering neuronal dysfunction and apoptosis. Sepsis-associated encephalopathy (SAE) is the
most frequent sepsis-associated organ dysfunction, with symptoms such as deliriums, seizures, and
coma, linked to increased mortality, morbidity, and cognitive disability. However, the current therapy
does not avoid those patients’ symptoms, evidencing the search for a more optimal approach. Herein
we focus on microglia as a prominent therapeutic target due to its multiple functions maintaining
CNS homeostasis and its polarizing capabilities, stimulating and resolving neuroinflammation
depending on the stimuli. Microglia polarization is a target of multiple studies involving nerve cell
preservation in diseases caused or aggravated by neuroinflammation, but in sepsis, its therapeutic
potential is overlooked. We highlight the peroxisome proliferator-activated receptor gamma (PPAR
)
neuroprotective properties, its role in microglia polarization and inflammation resolution, and the
interaction with nuclear factor- B (NF- B) and mitogen-activated kinases (MAPK), making PPAR
a
molecular target for sepsis-related studies to come.
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