Ano de Publicação: 2024
AUTORIA
Kelly Cattelan Bonorino a, Scheila Iria Kraus a, Gisele Henrique Cardoso Martins a, J´essica Jorge Probst b, D´ebora Melissa Petry Moeke c, Alice Henrique dos Santos Sumar d, Yuri Reis Casal e, Filipe Rodolfo Moreira Borges Oliveira f, Regina Sordi f, Jamil Assreuy f, Morgana Duarte da Silva a, Deborah de Camargo Hizume Kunzler g,* a Neurosciences, Federal University of Santa Catarina Brazil, Brazil b Federal University of Santa Catarina, Postgraduate Program in Biochemistry, Brazil c Department of Physical Therapy, University of British Columbia, Canada d Medical Sciences, Federal University of Santa Catarina, Brazil e Neuropathology, Department of Pathology, Medical School Hospital of the S˜ao Paulo University, Brazil f Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Brazil g Department of Physical Therapy, Santa Catarina State University, Brazil
RESUMO
Although studies have suggested an association between lung infections and increased risk of neuronal disorders
(e.g., dementia, cognitive impairment, and depressive and anxious behaviors), its mechanisms remain unclear.
Thus, an experimental mice model of pulmonary sepsis was developed to investigate the relationship between
lung and brain inflammation. Male Swiss mice were randomly assigned to either pneumosepsis or control groups.
Pneumosepsis was induced by intratracheal instillation of Klebsiella pneumoniae, while the control group received
a buffer solution. The model’s validation included assessing systemic markers, as well as tissue vascular
permeability. Depression- and anxiety-like behaviors and cognitive function were assessed for 30 days in sepsis
survivor mice, inflammatory profiles, including cytokine levels (lungs, hippocampus, and prefrontal cortex) and
microglial activation (hippocampus), were examined. Pulmonary sepsis damaged distal organs, caused peripheral
inflammation, and increased vascular permeability in the lung and brain, impairing the blood-brain barrier
and resulting in bacterial dissemination. After sepsis induction, we observed an increase in myeloperoxidase
activity in the lungs (up to seven days) and prefrontal cortex (up to 24 h), proinflammatory cytokines in the
hippocampus and prefrontal cortex, and percentage of areas with cells positive for ionized calcium-binding
adaptor molecule 1 (IBA-1) in the hippocampus. Also, depression- and anxiety-like behaviors and changes in
short-term memory were observed even 30 days after sepsis induction, suggesting a crosstalk between inflammatory
responses of lungs and brain.