Cerebral Glutamate Alterations Using Chemical Exchange Saturation Transfer Imaging in a Rat Model of Lipopolysaccharide-Induced Sepsis

使用化学交换饱和转移成像技术检测脂多糖诱发脓毒症大鼠模型中的脑谷氨酸变化

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作者:Do-Wan Lee, Jae-Im Kwon, Hwon Heo, Chul-Woong Woo, Na Hee Yu, Kyung Won Kim, Dong-Cheol Woo

Abstract

Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool to detect glutamate signal alterations caused by neuroinflammation. This study aimed to visualize and quantitatively evaluate hippocampal glutamate alterations in a rat model of sepsis-induced brain injury using GluCEST and proton magnetic resonance spectroscopy (1H-MRS). Twenty-one Sprague Dawley rats were divided into three groups (sepsis-induced groups (SEP05, n = 7 and SEP10, n = 7) and controls (n = 7)). Sepsis was induced through a single intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 5 mg/kg (SEP05) or 10 mg/kg (SEP10). GluCEST values and 1H-MRS concentrations in the hippocampal region were quantified using conventional magnetization transfer ratio asymmetry and a water scaling method, respectively. In addition, we examined immunohistochemical and immunofluorescence staining to observe the immune response and activity in the hippocampal region after LPS exposure. The GluCEST and 1H-MRS results showed that GluCEST values and glutamate concentrations were significantly higher in sepsis-induced rats than those in controls as the LPS dose increased. GluCEST imaging may be a helpful technique for defining biomarkers to estimate glutamate-related metabolism in sepsis-associated diseases.

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