1. Lung-brain crosstalk: Behavioral disorders and neuroinflammation in septic survivor mice
- Author
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Kelly Cattelan Bonorino, Scheila Iria Kraus, Gisele Henrique Cardoso Martins, Jéssica Jorge Probst, Débora Melissa Petry Moeke, Alice Henrique dos Santos Sumar, Yuri Reis Casal, Filipe Rodolfo Moreira Borges Oliveira, Regina Sordi, Jamil Assreuy, Morgana Duarte da Silva, and Deborah de Camargo Hizume Kunzler
- Subjects
Sepsis ,Lung inflammation ,Neuroinflammation ,Behavior ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
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.
- Published
- 2024
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