Dados do Trabalho

Título

PERIPHERAL INFLAMMATION DRIVES BRAIN GLUCOSE ABNORMALITIES

Fundamentação/Introdução

Sepsis induces severe peripheral inflammation, which seems to have strong effects on brain function. Long-term brain dysfunction is commonly observed among sepsis-survivors. In this context, brain inflammatory changes have been considered risk factors for developing dementia.

Objetivos

We aimed to evaluate whether sepsis would alter glucose metabolism indexed by [18F]fluorodeoxyglucose positron emission tomography (PET), an in vivo imaging biomarker of neurodegeneration. We hypothesize that a rat model of sepsis will present a widespread decline in in vivo brain glucose metabolism.

Delineamento e Métodos

Male Wistar rats (90 days old) were submitted to cecal ligation and perforation (CLP) to induce sepsis. 24 h later, animals were examined via Micro-PET [18F]FDG imaging. Volumes of interest (VOI) were chosen based on Alzheimer´s disease (AD) “hypometabolic signature”. Metabolic brain networks were constructed by computing Pearson correlation coefficients based on 10000 bootstrap samples. Graph theoretical measures such as density, global efficiency, small-worldness, assortativity coefficient, average degree and average clustering coefficient were calculated for each of the bootstrap samples.

Resultados

Whole brain [18F]FDG hypometabolism was observed in the CLP group (sham standardized uptake value [SUV] = 2.57±0.38; CLP SUV = 2.07±0.35). Sepsis induced ~20% hippocampal [18F]FDG hypometabolism (t25=3.636, P=0.0013) with local maxima in the hippocampal posterior area (peak t25=4.53; P=0.0007). Additionally, sepsis changed multiple connections within the metabolic network, promoting a widespread metabolic hyposynchronicity, especially in hippocampal and cortical areas (P<0.005, FDR corrected). Graph measures demonstrate a consistent reorganization in the brain metabolic network indexed by lower density, reduced global efficiency, assortativity, small-worldness, degree and clustering coefficient.

Conclusões/Considerações Finais

Our [18F]FDG PET regional analysis demonstrated a hypometabolism in several brain regions, including the hippocampus during sepsis. Additionally, metabolic network is hyposynchronic in the CLP group and graph measures revealed that brain regions are exchanging information less efficiently. These findings indicate that sepsis causes prominent glucose abnormalities similar to those observed in AD, which reinforces peripheral inflammation as a potential long-term risk factor for developing AD.

Referências

Michels et al., 2015; Young, 2010; Ziaja, 2013
Iwashyna et al., 2010
Godini and Fallahi, 2018; Tang et al., 2009

Palavras-chave

glucose metabolism; sepsis; [18F]FDG PET; brain inflammation.