thioacetamide and Memory-Disorders

Hepatic encephalopathy (HE) is a prevalent complication of the central nervous system (CNS) that is caused by acute or chronic liver failure. This study was designed to evaluate the effects of thymoquinone (TQ) on thioacetamide (TAA)-induced HE in rats, and determine the consequential behavioral, biochemical, and histological changes. HE was induced in male Wistar rats by intraperitoneal (i.p.) injection of 200 mg/kg TAA once every 48 h for 14 consecutive days. Control groups received the normal saline containing 5 % DMSO. Thymoquinone (5, 10, and 20 mg/kg) was administered for ten consecutive days intraperitoneally (i.p.) after HE induction and it was continued until the end of the tests. Then, the passive avoidance memory, extracellular single unit, BBB permeability, and brain water content were evaluated. Moreover, hippocampal tissues were used for evaluation of oxidative stress index, inflammatory biomarkers, and histological parameters following HE. As result of the treatment, TQ improved passive avoidance memory, increased the average number of simultaneous firing of spikes/bins, improved the integrity of BBB, and decreased brain water content in the animal model of HE. Furthermore, the results indicated that treatment with TQ decreased the levels of inflammatory cytokines (TNF-α and IL-1β) but increased the levels of glutathione (GSH) and anti-inflammatory cytokine (IL-10) of the surviving cells in the hippocampal tissues. This study demonstrates that TQ may have beneficial therapeutic effects on cognitive, oxidative stress, neuroinflammatory, and histological complications of HE in rat.

Topics: Animals; Benzoquinones; Glutathione; Hepatic Encephalopathy; Hippocampus; Inflammation; Interleukin-10; Interleukin-1beta; Male; Memory; Memory Disorders; Oxidative Stress; Rats; Rats, Wistar; Thioacetamide; Tumor Necrosis Factor-alpha

Tadalafil displays important neuroprotective effects in experimental models of neurodegenerative diseases, however its mechanisms of action remain poorly understood. The aim of the present study was to investigate the action of Tadalafil on learning and memory, neuroinflammation, glial cell activation and neuroprotection in the experimental model of hepatic encephalopathy (HE) induced by Thioacetamide (TAA) in mice.. Mice received intraperitoneal injections of TAA, for 3 consecutive days, reaching the final dose of 600 mg/kg. Tadalafil 15 mg/kg body weight was administered by gavage during 15 days after TAA induction. Mice underwent a Barnes maze for learning and memory evaluation.. Animals with hepatic encephalopathy showed reduced learning and spatial memory in the Barnes Maze, presented astrocyte and microglia activation and increased neuroinflammatory markers such as TNF-α, IL-1β, IL-6, p-p38, p-ERK and p-NF-kB. In addition, the signaling pathway PKA/PKG/CREB/BDNF/NeuN/synaptophysin and glutamate receptors were deregulated by TAA. Tadalafil treatment regulated the inflammation signaling pathways restoring learning and spatial memory.. Tadalafil significantly reduced neuroinflammation, promoted neuroprotection and plasticity, regulated the expression of hippocampal glutamate receptor and restored spatial learning ability and memory.

Topics: Animals; Astrocytes; Blotting, Western; CA1 Region, Hippocampal; Cerebral Cortex; Cytokines; Disease Models, Animal; Fluorescent Antibody Technique; Hepatic Encephalopathy; Injections, Intraperitoneal; Memory Disorders; Memory, Long-Term; Mice; Microglia; Neuronal Plasticity; Neuroprotective Agents; Nitric Oxide; Spatial Learning; Tadalafil; Thioacetamide

A behavioural evaluation was carried out on three chronic models of hepatic encephalopathy: two models of type B HE, portacaval shunt (PCS) and portal hypertension (PH) and one of type C HE with cirrhosis and portal hypertension from thioacetamide intoxication (TAA). The tasks selected cover a wide range of behaviours related to: locomotion (rotarod-accelerod test), anxiety (open field and elevated plus maze) and memory (Morris water maze). The results indicate that neither locomotor activity nor anxiety was affected in our models, in comparison with their respective controls. However, this is not the case for the mnesic tasks. Hence, the PCS and TAA groups displayed a severe alteration in spatial reference memory and cannot correctly perform the Morris maze task, while this alteration is less severe in the PH group. On the contrary, the PH group revealed a deficit in spatial working memory, like the TAA group, but this does not occur in subjects with PCS. These results reveal a double dissociation in spatial reference memory and spatial working memory between the PCS and PH groups, which would be of great interest to study about cerebral causes and substrates of the alterations accompanying HE.

Topics: Analysis of Variance; Animals; Anxiety; Disease Models, Animal; Exploratory Behavior; Hepatic Encephalopathy; Hypertension, Portal; Liver Cirrhosis, Experimental; Male; Maze Learning; Memory Disorders; Motor Activity; Portacaval Shunt, Surgical; Random Allocation; Rats; Rats, Wistar; Reaction Time; Spatial Behavior; Statistics, Nonparametric; Thioacetamide