HIPPOCAMPAL EARLY CHANGES IN A MINIMAL HEPATIC ENCEPHALOPATY RAT MODEL

PERAZZO JC, TALLIS S, CALTANA L, ARONNE MP, DELFANTE A, SOUTO P, REINES A, BRUSCO A.

Val-David

Congreso; 14th International Society on Hepatic Encephalopathy and Nitrogen Metabolism; 2010

ISHEN

     Graded portal-vein stenosis was used to induce rat minimal hepatic encephalopathy (MHE) whose main features are portal hypertension, moderate hyperammonemia and hippocampal mitochondrial alterations. These features were well established by day 14 post stenosis. We present a new view that shows the features on the 10th day after the stenosis in the rat hippocampus. Glial fibrillar acidic protein (GFAP) specific for astrocytes (A), S100b protein localized in the cytoplasm of A, Nestine (N) localized in A, perycites and endothelial cells (ECs), microtubule-associated protein 2 (MAP-2) and  neurofilament 200kDa,  dendritic markers, Lycopersicum esculentum (tomato lectin)  for microglia, and a Neuronal specific marker, were evaluated by immunohistochemistry. Beside this, Tripheniyltetrazolium (TTC) as a dye for hypoxic areas in rat’s brain and Hypoxia Inducible Factor 1a (HIF-1a) was evaluated by western blot technique and by immunohistochemistry. At day 10 A, GFAP + cells, were increased in number and with morphological changes as well as ECs, N +. TTC was highly positive in hippocampus and HIF-1a showed a significant increase in hippocampus at day 10, no significance differences were found in frontal cortex (day 10) and in both, hippocampus and frontal cortex at day 14. While Avoidance was altered at day 14 but no significant at day 10, analgesic effect was not observed at any time point. Taking whole data, alterations in the respiratory chain previously reported, astrogliosis and angiogenesis both with morphological changes and the surprisingly hippocampal hypoxia we can conclude that by now these are the earliest changes documented  in this model of MHE.      Graded portal-vein stenosis was used to induce rat minimal hepatic encephalopathy (MHE) whose main features are portal hypertension, moderate hyperammonemia and hippocampal mitochondrial alterations. These features were well established by day 14 post stenosis. We present a new view that shows the features on the 10th day after the stenosis in the rat hippocampus. Glial fibrillar acidic protein (GFAP) specific for astrocytes (A), S100b protein localized in the cytoplasm of A, Nestine (N) localized in A, perycites and endothelial cells (ECs), microtubule-associated protein 2 (MAP-2) and  neurofilament 200kDa,  dendritic markers, Lycopersicum esculentum (tomato lectin)  for microglia, and a Neuronal specific marker, were evaluated by immunohistochemistry. Beside this, Tripheniyltetrazolium (TTC) as a dye for hypoxic areas in rat’s brain and Hypoxia Inducible Factor 1a (HIF-1a) was evaluated by western blot technique and by immunohistochemistry. At day 10 A, GFAP + cells, were increased in number and with morphological changes as well as ECs, N +. TTC was highly positive in hippocampus and HIF-1a showed a significant increase in hippocampus at day 10, no significance differences were found in frontal cortex (day 10) and in both, hippocampus and frontal cortex at day 14. While Avoidance was altered at day 14 but no significant at day 10, analgesic effect was not observed at any time point. Taking whole data, alterations in the respiratory chain previously reported, astrogliosis and angiogenesis both with morphological changes and the surprisingly hippocampal hypoxia we can conclude that by now these are the earliest changes documented  in this model of MHE.