Disrupted metabolic and spontaneous neuronal activity of hippocampus in sepsis associated encephalopathy rats: A study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging.

Abstract

The diagnosis of sepsis associated encephalopathy (SAE) remains challenging in clinical settings because of a lack of specific biomarkers. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) can be used to aid in the diagnosis of cognition related diseases. This study investigated changes in functional activities and brain metabolites in the hippocampus in SAE rats by fMRI and 1H-MRS. Sepsis associated encephalopathy rats underwent cecal ligation and perforation (CLP) surgery. The Morris water maze (MWM) test was then used to evaluate cognitive function. Resting state-fMRI and 1H-MRS scanning were performed 7 and 14 days after CLP surgery to reveal spontaneous neuronal activity and metabolite changes in the hippocampus. The amplitude of low-frequency fluctuation (ALFF) was used to evaluate spontaneous neuronal activity in the hippocampus. Creatine (Cr), Myo-inositol (mI), and glutamine/glutamate (Glx) levels were measured with 1H-MRS scanning. Immunofluorescence and levels of interleukin (IL)-1β, interleukin (IL)-6, and C-reactive protein (CRP) in the hippocampus were additionally detected to evaluate microglial mediated inflammatory responses. Statistical analysis was performed to evaluate correlations between hippocampal metabolism and behavioral findings. Cecal ligation and perforation treated rats exhibited impaired learning and memory function in the MWM test at days 7 and 14. Elevation of IL-1β in the hippocampus, as well as immunofluorescence results, confirmed severe neuro inflammation in the hippocampus in SAE rats. Compared with the sham group, the ALFF of the right CA-1 area of the hippocampus was higher at day 7after CLP surgery. The Glx/Cr and mI/Cr ratios were enhanced at day 7 after CLP surgery and slightly lower at day 14 after CLP surgery. The ALFF value, and Glx/Cr and mI/Cr ratios were negatively correlated with time spent in the target quadrant in the MWM test. Spontaneous neuronal activity and metabolites showed significant alterations in SAE rats. The elevated ALFF value, Glx/Cr ratio, and mI/Cr ratio in the hippocampus were positively associated with cognitive deficits. Changes in ALFF and metabolites in hippocampus may serve as potential neuroimaging biomarkers of cognitive disorders in patients with SAE.