P33 Alcohol Aggravates Neurological Dysfunction and Leads to Permanent Cell Injury in Rats With Chronic Liver Disease
Bibliographic record
Abstract
Background: Hepatic encephalopathy (HE) is a debilitating neurological complication of chronic liver disease (CLD) with alcohol being a common etiological factor. However, excessive alcohol consumption has been shown to impact neurological integrity. To date, the influence of alcohol on the development of HE remains unclear. Therefore, we examined the effect of continuous alcohol consumption on neurological decline in rats with CLD induced via bile-duct ligation (BDL). Methods: Six-week BDL rats and Sham-operated controls were used. Day 7 after surgery, rats were administered alcohol (51% v/v ethanol) twice a day, for 5 straight days (3g/kg, via gavage) in a week for 4 weeks. Motor coordination (rotarod) and anxiety-like behavior (open field [OF] and elevated plus maze [EPM]) were assessed at day 40 (5 days after last gavage). Upon sacrifice, brains were collected, and western blot and immunohistochemical (IHC) analyses were used to investigate neuronal integrity in frontal cortex and cerebellum. Results: Alcohol further impaired motor coordination in BDL rats when compared to SHAM-Alcohol (P<0.01). Furthermore, BDL-Alcohol rats demonstrated an increase in anxiety-like behavior; increase in time spent in the closed arms of EPM and decrease in time spent in the center of the OF (P<0.05 vs SHAM-Alcohol). BDL-Alcohol rats demonstrated a decrease in neuronal markers of NeuN and SMI311 (P<0.01 and P<0.05, respectively) and astrocytic marker of GFAP (P<0.05), an increase in apoptotic markers of cleaved/pro-caspase3 (P<0.001), an increase in necroptosis markers of pRIP3 and pMLKL (P<0.01 and P<0.001, respectively), a decrease in total antioxidant capacity (P<0.001) and an increase in oxidative stress marker 4-HNE (P<0.05) in the cerebellum (not found in frontal cortex) compared to all groups. IHC results confirmed the colocalization of apoptotic marker (cleaved caspase3) and necroptosis marker (pMLKL) in neurons of the granular layer and astrocytes of the granular and Purkinje layer of the cerebellum of BDL-Alcohol rats. Conclusion: Continuous alcohol consumption exacerbates HE in BDL rats and leads to neuronal loss via apoptosis and necroptosis in the cerebellum with oxidative stress found as a triggering factor. These results demonstrate an adverse effect of continuous alcohol consumption on the development of HE and neuronal integrity in CLD.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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".