Inhibition of inflammation is not enough for recovery of cognitive impairment in hepatic encephalopathy: Effects of minocycline and ibuprofen

Abstract

There is evidence that hyperammonia and inflammation play crucial roles in hepatic encephalopathy. This study intends to determine neuroprotective effects of minocycline (MINO) and ibuprofen (IBU), and also set out to assess whether inhibition of inflammation is enough to achieve optimal improvement of hepatic encephalopathy symptoms.The hepatic encephalopathy was induced by bile-duct ligation (BDL), and the animals received first dose of MINO and/or IBU 15 days later and then every day until the 28 day. The rats were divided into the 6 groups of control, sham, BDL + V and BDL + IBU, BDL + MINO and BDL + MINO + IBU, which each group had 3 sub-groups for evaluations of blood-brain barrier (BBB), memory performance, synaptic-plasticity and apoptosis. The long-term potentiation (LTP) and short-term potentiation were evaluated by field potential recording. The memory performance, apoptosis and BBB integrity were assessed via passive avoidance, Western-blotting of caspase-3 and Evans-blue dye extravasation, respectively.The MINO, IBU or their co-treatment in the BDL rats did not improve liver dysfunction. The BDL increased hippocampal apoptosis and BBB disruption, which were fully recovered by all three pharmacological interventions. The MINO treatment alone or combined with IBU had similar neuroprotective effects on the BDL-induced disturbances of hippocampal basal synaptic transmission, LTP and memory performance, whereas they were not ameliorated by the single IBU therapy.Therefore, it seems likely that inhibition of inflammation is not able to improve functionally impaired memory and LTP in the hepatic encephalopathy, and they may be recovered by the direct neuroprotective effects of the MINO.