Neuroinflammatory and behavioral changes following experimental Klebsiella pneumoniae pneumonia: involvement of vagal signaling in the lung-brain axis

Pneumonia can trigger persistent neurological changes. We investigated the neurobehavioral and neuroinflammatory consequences of experimental Klebsiella pneumoniae pneumonia and the role of vagal signaling. Male Wistar rats were assigned to three groups: SHAM, undergoing surgery without vagal sectioning and intratracheal saline instillation (n=15); KLEB, undergoing intratracheal instillation of K. pneumoniae (1×10⁹ colony-forming units/animal; n=12); and VAGO+KLEB, undergoing posterior subdiaphragmatic vagotomy and similar bacterial inoculation (n=13). Clinical status was monitored until day 14. On day 15, open-field and object recognition tests were performed; on day 16, diffuse alveolar damage (DAD) and neuroinflammation were evaluated by IBA-1 and GFAP immunostaining and Sholl analysis. Infected groups showed persistent clinical deterioration up to day 14 (KLEB: p=0.015; VAGO+KLEB: p=0.007 vs. SHAM). Pneumonia increased DAD in KLEB and VAGO+KLEB compared to SHAM (p<0.001 for both). Infected animals showed a reduced center/total velocity ratio in the open field (KLEB: p=0.002; VAGO+KLEB: p=0.001), with preserved overall locomotor capacity. In the object recognition test, the SHAM group explored the novel object more (p=0.001), whereas the KLEB group explored the familiar object more (p=0.003); the VAGO+KLEB group showed no significant preference. IBA-1 analysis revealed an alteration in microglial branching in the dentate gyrus between the SHAM and KLEB groups (p=0.0214). GFAP analysis revealed a difference in astrocytic arborization in the prefrontal cortex between the KLEB and VAGO+KLEB groups (p=0.0177). Vagotomy did not consistently exacerbate the evaluated outcomes. The findings demonstrate persistent neurofunctional and neuroinflammatory repercussions following pneumonia and reinforce the concept of lung-brain communication, suggesting additional mechanisms independent of vagal integrity.