Bile ‐duct ligation renders the brain susceptible to hypotension induced neuronal degeneration: implications of ammonia

AbstractHepatic encephalopathy (HE) is a debilitating neurological complication of cirrhosis. By definition, HE is considered a reversible disorder, and therefore HE should resolve following liver transplantation (LT). However, persisting neurological complications are observed in as many as 47% of LT recipients. LT is an invasive surgical procedure accompanied with various perioperative factors such as blood loss and hypotension which could influence outcomes post ‐LT. We hypothesize that minimal HE (MHE) renders the brain frail and susceptible to hypotension‐induced neuronal cell death. Six‐week bile duct‐ligated (BDL) rats with MHE and respective SHAM‐controls were used. Several degrees of hypotension (mean arterial pressure of 30, 60 and 90mmHg) were induced via blood withdrawal from the femoral artery and maintained for 120 minutes. Brains were collected for neuronal cell count and apoptotic analysis. In a separate group, BDL rats were treated for MHE with the ammonia‐lowering strategy ornithine phenylacetate (OP; MNK‐6105), administer ed orally (1g/kg) for 3 weeks before induction of hypotension. Hypotension 30 and 60mmHg (not 90mmHg) significantly decreased neuronal marker expression (NeuN) and cresyl violet staining in the frontal cortex compared to respective hypotensive SHAM‐operated controls as well as non‐hypotensive BD L rats. Neuronal degeneration was associated with an increase in cleaved caspase‐3, suggesting the mechanism of cell death was...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research