Inflammatory response and long-term behavioral assessment after neonatal CO₂-pneumothorax: study in a rodent model

Background: Carbon-dioxide (CO₂)-pneumothorax during minimally invasive surgery induces well-known metabolic changes. However, little is known about its impact on the central nervous system. The aim of this work is to evaluate the acute impact of CO₂-pneumothorax over central cytokine response and its long-term effect on animal behavior.

Methods: This is an experimental study where neonatal Sprague-Dawley rats are submitted to CO₂-pneumothorax. Peripheral and central cytokine response was evaluated 24h after insufflation, and peripheral immune cell phenotyping was evaluated 24h and 4weeks post-insufflation. Progenitor cell survival was evaluated in the hippocampal dentate gyrus, and the behavioral analysis was performed in adulthood to test cognition, anxious-like, and depressive-like behavior.

Results: Significantly increased IL-10 levels were observed in the cerebrospinal-fluid (CSF) of animals submitted to CO₂-pneumothorax, while no differences were found in serum. Regarding pro-inflammatory cytokines, no differences were observed in the periphery or centrally. CO₂-pneumothorax event did not alter the survival of newborn cells in the hippocampal dentate gyrus, and no impact on long-term behavior was observed.

Conclusions: Neonatal animals submitted to CO₂-pneumothorax present acutely increased CSF IL-10 levels. The CO₂-pneumothorax seems to result in no significant outcome over neurodevelopment as no functional behavioral alterations were observed in adulthood.