Lung-brain crosstalk: Behavioral disorders and neuroinflammation in septic survivor mice

• Published in: Brain, behavior, & immunity. Health Vol. 40; p. 100823
• Main Authors: Bonorino, Kelly Cattelan, Iria Kraus, Scheila, Henrique Cardoso Martins, Gisele, Jorge Probst, Jéssica, Petry Moeke, Débora Melissa, Henrique dos Santos Sumar, Alice, Reis Casal, Yuri, Rodolfo Moreira Borges Oliveira, Filipe, Sordi, Regina, Assreuy, Jamil, Duarte da Silva, Morgana, de Camargo Hizume Kunzler, Deborah
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2024; Elsevier
• Subjects: Behavior; from the Special Issue on Emerging PNI research: future leaders in focus; Edited by Amanda Kentner, Lois Harden, Denis de Melo Soares and Christoph Rummel; Lung inflammation; Neuroinflammation; Sepsis; Sepsis; Neuroinflammation; Lung inflammation; Behavior
• ISSN: 2666-3546; 2666-3546
• DOI: 10.1016/j.bbih.2024.100823

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. •Pneumosepsis resulted in persistent neuroinflammation in mice.•Pneumosepsis also causes anxiety, depressive-like behaviors, and cognitive impairment.•Pneumosepsis resulted in acute tissue permeability and increased myeloperoxidase in the brain.•Also, pneumosepsis model induced microglial activation in hippocampus.•Neuroinflammation shows the crosstalk between lung damage and brain dysfunction.