Mapping the Alterations of Glutamate Using Glu-Weighted CEST MRI in a Rat Model of Fatigue

Li, Ruili; Dai, Zhuozhi; Hu, Di; Zeng, Heng; Zeman, Florian; Zhuang, Zerui; Xu, Haiyun; Huang, Qingjun; Cui, Yilong; Zhang, Handi

doi:10.3389/fneur.2020.589128

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Glu CEST acquires CEST signals of 3.0 ppm with a high irradiation power and is suggested to indicate Glu in the brain. 8 Glu CEST may be associated with astrocyte proliferation in neuroinflammatory diseases, demonstrating its potential to be used as a neuroimaging biomarker for gliosis. 9 Hence, DKI and Glu CEST may be used in combination to better reveal the physiological and pathological metabolic changes in the brain in sepsis-associated encephalopathy.…”

Section: Introductionmentioning

confidence: 99%

“…A selective radiofrequency pulse saturates the exchangeable protons and transfers the saturation effect to the water molecules through a chemical exchange in CEST, causing a reduction in the MR signals of the water molecules and indirectly reflecting the substance concentration. Glu CEST acquires CEST signals of 3.0 ppm with a high irradiation power and is suggested to indicate Glu in the brain . Glu CEST may be associated with astrocyte proliferation in neuroinflammatory diseases, demonstrating its potential to be used as a neuroimaging biomarker for gliosis .…”

Section: Introductionmentioning

confidence: 99%

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Role of Imaging Modalities and N-Acetylcysteine Treatment in Sepsis-Associated Encephalopathy

Zhong

Guan

et al. 2023

ACS Chem. Neurosci.

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Sepsis-associated encephalopathy is a severe systemic infection complication. Although early stages involve pathophysiological changes, detection using conventional imaging is challenging. Glutamate chemical exchange saturation transfer and diffusion kurtosis imaging can noninvasively investigate cellular and molecular events in early disease stages using magnetic resonance imaging (MRI). N-Acetylcysteine, an antioxidant and precursor of glutathione, regulates neurotransmitter glutamate metabolism and participates in neuroinflammation. We investigated the protective role of n-acetylcysteine in sepsis-associated encephalopathy using a rat model and monitored changes in brain using magnetic resonance (MR) molecular imaging. Bacterial lipopolysaccharide was injected intraperitoneally to induce a sepsis-associated encephalopathy model. Behavioral performance was assessed using the open-field test. Tumor necrosis factor α and glutathione levels were detected biochemically. Imaging was performed using a 7.0-T MRI scanner. Protein expression, cellular damage, and changes in blood–brain barrier permeability were assessed using western blotting, pathological staining, and Evans blue staining, respectively. Lipopolysaccharide-induced rats showed reduced anxiety and depression after treatment with n-acetylcysteine. MR molecular imaging can identify pathological processes at different disease stages. Furthermore, rats treated with n-acetylcysteine showed increased glutathione levels and decreased tumor necrosis factor α, suggesting enhanced antioxidant capacity and inhibition of inflammatory processes, respectively. Western blot analysis showed reduced expression of nuclear factor kappa B (p50) protein after treatment, suggesting that n-acetylcysteine inhibits inflammation via this signaling pathway. Finally, n-acetylcysteine-treated rats showed reduced cellular damage by pathology and reduced extravasation of their blood–brain barrier by Evans Blue staining. Thus, n-acetylcysteine might be a therapeutic option for sepsis-associated encephalopathy and other neuroinflammatory diseases. Furthermore, noninvasive “dynamic visual monitoring” of physiological and pathological changes related to sepsis-associated encephalopathy was achieved using MR molecular imaging for the first time, providing a more sensitive imaging basis for early diagnosis, identification, and prognosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Imaging Modalities and N-Acetylcysteine Treatment in Sepsis-Associated Encephalopathy

Zhong

Guan

et al. 2023

ACS Chem. Neurosci.

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Why does malaise/fatigue occur? Underlying mechanisms and potential relevance to treatments in rheumatoid arthritis

Tanaka,

Ikeda,

Kaneko

et al. 2024

Expert Review of Clinical Immunology

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Role of imaging modalities and N-acetylcysteine treatment in sepsis-associated encephalopathy

Zhong

Guan

et al. 2023

Preprint

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Background Sepsis-associated encephalopathy is a severe complication due to systemic infection. Although early stages involve pathophysiological changes, detection using conventional imaging is challenging. Glutamate chemical exchange saturation transfer and diffusion kurtosis imaging can noninvasively investigate cellular and molecular events in the early stage of the disease by MRI. N-acetylcysteine, an antioxidant and precursor of glutathione, regulates the metabolism of the neurotransmitter glutamate and participates in neuroinflammation. We aimed to investigate the protective role of n-acetylcysteine in sepsis-associated encephalopathy using a rat model and monitor changes in the brain using magnetic resonance molecular imaging. Methods Bacterial lipopolysaccharide was injected intraperitoneally into the rats to induce a sepsis-associated encephalopathy model. The behavioural performance was assessed using the open field test. Tumour necrosis factor alpha and glutathione levels were detected biochemically. Imaging was performed using a 7.0-T MRI scanner. Protein expressions and cellular damage were assessed by western blotting and pathological staining, respectively. We also evaluated changes in the blood-brain barrier permeability by the Evans blue staining. Results The lipopolysaccharide-induced rats showed reduced anxiety and depression after treatment with n-acetylcysteine. Magnetic resonance molecular imaging can identify pathological processes at different stages of the disease. Furthermore, rats treated with n-acetylcysteine showed increased glutathione levels and decreased tumour necrosis factor alpha, suggesting enhanced antioxidant capacity and inhibition of inflammatory processes, respectively. Western blot analysis showed a reduced expression of nuclear factor kappa B (p50) protein after treatment, suggesting that n-acetylcysteine inhibits inflammation via this signalling pathway. Finally, n-acetylcysteine treated rats also showed reduced cellular damage by pathology and reduced extravasation of their blood-brain barrier by Evan Blue staining. Conclusion This study showed that n-acetylcysteine might be a therapeutic option for sepsis-associated encephalopathy and other neuroinflammatory diseases. Furthermore, non-invasive ‘dynamic visual monitoring’ of the physiological and pathological changes related to sepsis-associated encephalopathy was achieved for the first time using magnetic resonance molecular imaging, which provides a more sensitive imaging basis for early clinical diagnosis, identification, and prognosis.

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Mapping the Alterations of Glutamate Using Glu-Weighted CEST MRI in a Rat Model of Fatigue

Cited by 3 publications

References 41 publications

Role of Imaging Modalities and N-Acetylcysteine Treatment in Sepsis-Associated Encephalopathy

Role of Imaging Modalities and N-Acetylcysteine Treatment in Sepsis-Associated Encephalopathy

Why does malaise/fatigue occur? Underlying mechanisms and potential relevance to treatments in rheumatoid arthritis

Role of imaging modalities and N-acetylcysteine treatment in sepsis-associated encephalopathy

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