1. The effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [ 18 F]PBR146 in-vivo neuroinflammation imaging study.
- Author
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Kong X, Luo S, Wu SY, Zhang J, Yang GF, Lu GM, and Zhang LJ
- Subjects
- Animals, Rats, Male, Positron Emission Tomography Computed Tomography, Disease Models, Animal, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases diagnostic imaging, Gastrointestinal Agents pharmacology, Gastrointestinal Agents administration & dosage, Brain diagnostic imaging, Brain drug effects, Brain metabolism, Fluorine Radioisotopes, Carrier Proteins, Receptors, GABA-A, Hepatic Encephalopathy drug therapy, Hepatic Encephalopathy diagnostic imaging, Hepatic Encephalopathy metabolism, Rifaximin pharmacology, Lactulose pharmacology, Rats, Sprague-Dawley
- Abstract
Introduction: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [
18 F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18 F]PBR146 micro-PET/CT., Methods: Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses., Results: The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [18 F]PBR146 in BDL+NS group was significantly higher than other groups (p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella., Conclusions: RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [18 F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)- Published
- 2024
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