Chronic brain changes caused by severe systemic inflammatory episode

Background Sepsis‐associated encephalopathy (SAS) is a neurological complication of a severe systemic inflammatory episode that compromises brain function. This neurological impairment can lead to cognitive dysfunction that appears to precede neurodegenerative disorders such as Alzheimer’s disease. However, the events by which systemic inflammation causes such significant damage to the brain are not yet fully established. With that in mind, this study sought to investigate persistent brain changes after a severe systemic inflammatory episode. Method Male Wistar rats (90 days old) were divided into two experimental groups: sham (n = 33) and sepsis (n = 37). For the induction of severe systemic inflammation, the animals underwent cecal ligation and perforation (CLP). Animals were followed for 30, 60 and 120 days. In all time‐points, we performed the object recognition task to evaluate declarative memory and Western Blotting to assess astrocyte‐related proteins (GFAP, GLT‐1 and Mao‐B). At 30 and 120 days, we evaluated the ΒBB integrity [cerebrospinal fluid (CSF) albumin levels and cellularity by HCLP] and brain glucose metabolism (FDG‐PET imaging). Result Our results show that CLP model compromised long‐term memory at 60 and 120 days. Furthermore, we found higher levels of albumin in the CSF in CLP animals compared to sham at 30 (p = 0.023) and 120 days post‐sepsis (p = 0.002). In addition, we also observed an increase in CSF cellularity in CLP animals after 30 days after sepsis induction. We also found persistent glucose whole brain hypometabolism at 30 (local maxima, t (12) = ‐3.7) and 120 days (local maxima, t (9) = ‐8.45), suggesting persistent metabolic abnormalities. Finally, we observed changes in astrocyte‐related proteins. At 30 days, hippocampal GLT‐1 (p<0.001) and cortical GFAP (p < 0.0001) immunocontents were reduced in CLP rats compared to sham. At 60 days, we observed decreased hippocampal GFAP (p < 0,05) and MAO‐B (p < 0.01) immunocontents. At 120 days, we found decreased MAO‐B in the hippocampus (p<0.05). Conclusion We found that a severe systemic inflammation episode causes persistent changes in brain glucose metabolism and BBB integrity, which seems associated with long‐term memory impairment. In addition, astrocytes seem to be reacting by changing their protein expression, a typical feature of reactive astrocytes.