The effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [ ¹⁸ F]PBR146 in-vivo neuroinflammation imaging study.

Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101570837 Publication Model: Print Cited Medium: Internet ISSN: 2162-3279 (Electronic) NLM ISO Abbreviation: Brain Behav Subsets: MEDLINE

Original Publication: Hoboken, NJ : John Wiley & Sons

Hepatic Encephalopathy*/drug therapy ; Hepatic Encephalopathy*/diagnostic imaging ; Hepatic Encephalopathy*/metabolism ; Rifaximin*/pharmacology ; Lactulose*/pharmacology ; Rats, Sprague-Dawley*; 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

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.)

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82230068 National Natural Science Foundation of China; 81830057 National Natural Science Foundation of China; 81322020 National Natural Science Foundation of China; 81230032 National Natural Science Foundation of China; 811713 to LJZ National Natural Science Foundation of China; 81401468 to GFY National Natural Science Foundation of China; 81601486 to SL National Natural Science Foundation of China; 82127806 to GML National Natural Science Foundation of China; 2020AAA0109500 to GML The Science and Technology Innovation 2030-Major Projects; 021414380531 to GML Fundamental Research Funds for the Central Universities; 201801B055 to XK The program B for Outstanding Ph.D. candidate of Nanjing University

Keywords: hepatic encephalopathy; lactulose; neuroinflammation; positron emission tomography; rifaximin

L36O5T016N (Rifaximin)
4618-18-2 (Lactulose)
0 (Gastrointestinal Agents)
141440-82-6 (Tspo protein, rat)
0 (Fluorine Radioisotopes)
0 (Carrier Proteins)
0 (Receptors, GABA-A)

Date Created: 20240706 Date Completed: 20240706 Latest Revision: 20240708

20240708

PMC11226542

10.1002/brb3.3621

38970239