Severe systemic inflammation promotes persistent brain metabolic abnormalities

Abstract

AbstractBackgroundSevere systemic inflammation can spread to the central nervous system, promoting neuronal dysfunction. Individuals who survive to a severe inflammatory episode, have greater chances to develop cognitive impairment. In this context, brain inflammatory changes have been considered a risk factor for Alzheimer’s disease (AD). We previously demonstrated, a significant [18F]FDG hypometabolism 24 h after the induction of severe systemic inflammation by cecal ligation and perforation (CLP), a sepsis model. However, whether severe systemic inflammation causes long‐term effects on brain energy metabolism remains unclear. Here, we aim at Investigating persistent consequences of a severe systemic inflammatory episode on brain energy metabolism. We hypothesized that brain energetic metabolism does not completely recover from a systemic inflammatory episode, which could be a trigger for neurodegeneration.MethodWistar rats (90 days old) were submitted to CLP and, examined in vivo via Micro‐PET [18F]FDG imaging 30 days later. Albumin and cellularity in the cerebrospinal fluid (CSF) were assessed by HPLC and flow cytometry, respectively, as an index of blood brain barrier (BBB) integrity. HPLC was also used for evaluating glutamate levels in CSF and glutamate uptake was evaluated in hippocampal and cortical slices using a radioactive assay.ResultWe found a persistent brain [18F]FDG hypometabolism in the CLP group. A 4‐fold increase in albumin levels was observed, along with a prominent increase in cellularity in the CSF of CLP animals. Additionally, decreased glutamate uptake in cortex (32%) and hippocampus (16%) along with increased levels of glutamate in CSF was found in the CLP group (Figure 1).ConclusionThese results that an episode of severe systemic inflammatory causes persistent brain metabolic disturbances and BBB damage. It is very likely that the long period of BBB disruption, allowing for communication between peripheral mediators/cells and the brain, compromises brain energy metabolism. Together, these findings suggest a link between peripheral inflammation and neurodegeneration.