Speaker
Description
Advanced liver disease is a life-threatening condition that can result in multiple severe complications, including hepatic encephalopathy (HE). HE is a brain dysfunction caused by impaired liver function due to various underlying etiologies. Under cirrhosis, up to 80% of patients can develop HE and exhibit memory deterioration. The pathophysiological mechanism underlying memory dysfunction in HE is unknown. Microglia activation/neuroinflammation and altered neuroplasticity might be responsible for memory abnormalities observed in HE patients. The aims of the present investigation were to assess memory function and identify microglial changes in a chronic model of HE (CHE). The study was carried out in 5 months-male Wistar rats with chronic liver disease induced by thioacetamide (TAA, 100mg/kg. b.w) administration. Memory function was assessed by Morris water maze test (MWM), Novel object recognition test and Y-maze test, together with microglial marker Iba1 (for activation) within the cerebral cortex, the hippocampal CA1, CA3 and dentate gyrus (DG) along with brain ammonia and proinflammatory cytokines’ measurement by ELISA. Our data showed memory impairment in our TAA treated rats with significant elevation of microglia activation in the CA1, CA3, and DG of the hippocampal formation. Additionally, we showed a 3-fold increase of brain ammonia and upregulation of proinflammatory cytokines; TNF-α, IL-1β, and Il-6. This strongly suggest that hyperammonemia and microglia activation/neuroinflammation underlie cognitive impairment associated with advanced liver disease.
Key words: hepatic encephalopathy, hippocampus, Iba1, memory, microglia activation, brain cytokines, ammonia.
