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

Abstract

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.