Impacto da pneumonia grave no sistema nervoso centralefeitos de curto e longo prazo

Pneumonia is defined as an acute inflammation of the lower respiratory tract and affects about 450 million people worldwide. Pneumonia can result from infection by bacteria, viruses and fungi and are classified as community-acquired pneumonia and nosocomial pneumonia. This disease can also cause a pulmonary complication, known as acute respiratory distress syndrome (ARDS), characterized by endothelial damage with increased capillary permeability, fluid protein extravasation in the alveolar space and pulmonary edema. This most severe form can that lead to systemic inflammation with subsequent multiple organ failure and sepsis. Severe infectious diseases such as pneumonia, can cause long-term changes, such as CNS (central nervous system) involvement. The pathophysiology of encephalopathy associated with systemic inflammation is still limited and the development of new experimental models that are clinically relevant can help to clarify the mechanisms involved in encephalopathy, and act as a tool for the study of therapeutic strategies to contain or reverse the possible formation of neurocognitive sequelae. The main objective of this study was to investigate the neuroinflammatory mechanisms associated with the cognitive decline in an experimental model of severe pneumonia. First, we validated a severe pneumonia model able to mimic the clinical manifestations of the disease. C57BL/6 mice were divided into control group and pneumonia group (PA103). The control group received 50 µL of saline solution by intratracheal instillation and the pneumonia group received 50 µL of a solution containing 104 or 105 CFU of the bacteria Pseudomonas aeruginosa 103, also by intratracheal instillation The local and systemic inflammatory processes and histopathology in the lungs of the animals submitted to bacterial pneumonia model were analyzed. The model led to a decrease in the survival of animals and increased their clinical score. We also observed that intratracheal instillation of PA103 resulted in an intense cell migration into the lung parenchyma, accompanied by pulmonary edema formation and increased local and systemic cytokines, as well as a decline in lung function. In addition, the severe pneumonia model stablished in this study was able to induce significant changes in the CNS. The acute changes included microglial activation, increase in inflammatory mediators, the presence of oxidative stress and reduction in synaptic proteins. The long-term changes included cognitive dysfunction 13 days after lung insult, which unlike polymicrobial sepsis model, remained for 30 and 50 days after challenge. Our analysis also showed persistent decrease in synaptic proteins observed in the early time-point. Our study, therefore, presents an experimental pneumonia model possibly capable to induce a permanent cognitive impairment. Moreover, evidence of cognitive decline and long-term synaptic dysfunction presented in the addressed model provides another clinically relevant tool for the study of cerebral impairment seen in neuropathologies, specially those involving the interaction between peripheral inflammatory response and CNS