P32 Multiple Ammonia-Induced Episodes of Hepatic Encephalopathy Provoke Neuronal Cell Loss in Bile-Duct Ligated Rats
Bibliographic record
Abstract
Background: Hepatic encephalopathy (HE) is a major complication of chronic liver disease (CLD). This neurological disorder is known to be reversible following liver transplantation (LT). Retrospective studies have demonstrated an association between a history of HE episodes and poor neurological outcome following LT. However, the impact of HE episodes on the brain remains unknown. Our aim was to evaluate the impact of multiple episodes on neurological status and brain injury in rats with CLD. Method: Five-week BDL rats and Sham-operated controls were used. BDL rats were injected with ammonium acetate, precipitating an overt episode of HE every 4 days from week 3 post-surgery (total; 4 episodes). Sham rats also received ammonia and control rats received saline. Three days after the last episode, short- and long-term memory (LTM) were assessed. Upon sacrifice, plasma and brains were collected for oxidative stress measurements and western blot used to investigate neuronal integrity in frontal cortex, hippocampus, and cerebellum. Proteomic analysis was performed on hippocampal tissue samples. Results: LTM was found to be impaired in both BDL-Vehicle and BDL-Ammonia groups vs respective Sham. However, LTM impairment was further aggravated in BDL-Ammonia rats. In BDL-Ammonia, GFAP and apoptotic markers (cleaved caspase-3 and Bax/Bcl2) were increased in the hippocampus, whereas neuronal markers (NeuN and SMI311) were reduced compared to all other experimental groups. Plasma oxidative stress was increased in BDL-Ammonia compared to respective Sham and BDL rats. Decreased total antioxidant capacity and increased 4-HNE levels were found in the hippocampus of the BDL-Ammonia group compared to respective sham and BDL rats. These differences observed in the multiple episodic BDL rats were not demonstrated following one episode. Proteomic analysis revealed 2 proteins which significantly altered in BDL-Ammonia compared to BDL-Vehicle and respective Sham. Conclusion: Multiple episodes of overt HE exacerbated the neurological impairments in BDL rats. LTM impairment in the BDL-Ammonia rats was associated with increased oxidative stress, apoptotic markers and decreased neuronal markers in the hippocampus, suggesting neuronal injury/loss. Elevated levels of GFAP in the hippocampus insinuate gliosis. These results suggest that cumulative HE episodes may cause permanent cell damage and, therefore, will less likely reversible following LT.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".