Background and Aims: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, and it is understood to be reversible following liver transplantation (LT). However, up to 47% of LT patients have been documented to have persisting neurological complications associated with a history of overt HE episodes. We hypothesize that episodes of HE will accelerate neurological deterioration. Our goal was to evaluate the impact of cumulative HE episodes on neurological status and brain injury in cirrhotic rats.
Method: Five-week bile-duct ligation (BDL) rats and Sham-operated controls were divided into episodic and non-episodic groups. Episodes of HE were induced every 4 days starting week 3 post-BDL following injection of ammonium acetate. 3 days following the last injection, neurological status was assessed. Upon sacrifice, brains were collected for western blot analysis; Neuronal nuclei (NeuN), caspase-3, and GFAP were measured.
Results: Long-term memory (LTM) was impaired in both non- and episodic BDL groups vs respective controls and was further aggravated in episodic BDL rats. Both GFAP and caspase-3 protein expression were significantly increased, whereas NeuN was significantly decreased in the hippocampus of episodic BDL rats vs non-episodic BDL rats.
Conclusion: HE episodes exacerbate neurological impairments in BDL rats. LTM impairment was associated with an increase in caspase-3 and a decrease in NeuN in the hippocampus, which suggests neuronal injury/loss. Elevated levels of GFAP in the hippocampus insinuates gliosis as a consequence of neuronal loss. These results suggest that multiple episodes of HE may cause permanent cell damage, leading to persisting neurological complications post-LT.