biostudies-literatureKong XFundamental Research Funds for the Central UniversitiesNational Natural Science Foundation of ChinaThe Science and Technology Innovation 2030-Major ProjectsThe program B for Outstanding Ph.D. candidate of Nanjing Universitye3621https://www.ebi.ac.uk/biostudies/studies/S-EPMC11226542biostudies-literatureUnknown14(7)<h4>Introduction</h4>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. [¹⁸F]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 [¹⁸F]PBR146 micro-PET/CT.<h4>Methods</h4>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.<h4>Results</h4>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 [¹⁸F]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.<h4>Conclusions</h4>RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [¹⁸F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.Brain and behaviorThe effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [¹⁸F]PBR146 in-vivo neuroinflammation imaging study.PMC112265428183005781230032811713 to LJZ8132202081601486 to SL201801B055 to XK82127806 to GML81401468 to GFY2020AAA0109500 to GML82230068021414380531 to GMLYang GFZhang JWu SYZhang LJLu GMLuo SKong XfalseThe effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [¹⁸F]PBR146 in-vivo neuroinflammation imaging study.<h4>Introduction</h4>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. [¹⁸F]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 [¹⁸F]PBR146 micro-PET/CT.<h4>Methods</h4>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.<h4>Results</h4>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 [¹⁸F]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.<h4>Conclusions</h4>RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [¹⁸F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.2024-01-01T00:00:00Z2024 Jul2025-04-22T15:29:12.622Z2025-04-06T01:25:53.307ZS-EPMC112265423897023910.1002/brb3.3621