Assessing long-term neuroinflammatory responses to encephalopathy using MRI approaches in a rat endotoxemia model

Abstract

Sepsis-associated encephalopathy (SAE) induces neuroinflammation, which is associated with cognitive impairment (CI). CI is also correlated with aging. We used contrast-enhanced magnetic resonance imaging (MRI), perfusion MRI, and MR spectroscopy to assess long-term alterations in BBB permeability, microvascularity, and metabolism, respectively, in a rat lipopolysaccharide-induced SAE model. Free radical-targeted molecular MRI was used to detect brain radical levels at 24h and 1week post-LPS injection. CE-MRI showed increased Gd-DTPA uptake in LPS rat brains at 24h in cerebral cortex, hippocampus, thalamus, and perirhinal cortex regions. Increased MRI signal intensities were observed in LPS rat brains in cerebral cortex, perirhinal cortex, and hippocampus regions 1week post-LPS. Long-term BBB dysfunction was detected in the cerebral cortex at 6weeks post-LPS. Increased relative cerebral blood flow (rCBF) in cortex and thalamus regions at 24h, decreased cortical and hippocampal rCBF at 6weeks, decreased cortical rCBF at 3 and 12weeks, and increased thalamus rCBF at 6weeks post-LPS, were detected. MRS indicated that LPS-exposed rat brains had decreased: NAA/Cho metabolite ratios at 1, 3, 6, and 12weeks; Cr/Cho at 1, 3, and 12weeks; and Myo-Ins/Cho at 1, 3, and 6weeks post-LPS. Free radical imaging detected increased radical levels in LPS rat brains at 24h and 1week post-LPS. LPS-exposed rats were compared to saline-treated controls. We clearly demonstrated BBB dysfunction, impaired vascularity, and decreased brain metabolites, as measures of long-term neuroinflammatory indicators, as well as increased free radicals in a LPS-induced rat SAE model.