A5062390725- Neuroscience and Neuropharmacology Research
- Liver Disease and Transplantation
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Epilepsy research and treatment
- Diet and metabolism studies
- Infectious Encephalopathies and Encephalitis
- Neurological Complications and Syndromes
- Nitric Oxide and Endothelin Effects
- Organ Transplantation Techniques and Outcomes
- Pharmacological Effects and Toxicity Studies
- Memory and Neural Mechanisms
- Anesthesia and Neurotoxicity Research
- Biochemical effects in animals
- Toxic Organic Pollutants Impact
- Pesticide Exposure and Toxicity
- Extracellular vesicles in disease
- Heavy Metal Exposure and Toxicity
- Tryptophan and brain disorders
- Ion channel regulation and function
- Molecular Sensors and Ion Detection
- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
Centro de Investigacion Principe Felipe
2016-2025
INCLIVA Health Research Institute
2019
Instituto de Biomedicina de Valencia
1997-2005
Instituto Valenciano de Investigaciones Agrarias
2002
Patients with liver cirrhosis and minimal hepatic encephalopathy (MHE) show mild cognitive impairment spatial learning dysfunction. Hyperammonemia acts synergistically inflammation to induce in MHE. Hyperammonemia-induced neuroinflammation hippocampus could contribute Two main aims of this work were: (1) assess whether chronic hyperammonemia increases inflammatory factors the if is associated microglia and/or astrocytes activation (2) hyperammonemia-induced altered membrane expression...
Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive motor impairment hepatic encephalopathy (HE). The link between remains unknown. New treatments reducing could improve neurological impairment. aims were, hyperammonemic rats, assess whether: (a) Enhancing endogenous anti-inflammatory mechanisms by sulforaphane treatment reduces restores learning coordination. (b) Reduction of normalizes extracellular GABA glutamate-NO-cGMP...
Enhanced GABAergic neurotransmission contributes to impairment of motor coordination and gait cognitive function in different pathologies, including hyperammonemia hepatic encephalopathy. Neuroinflammation is a main contributor enhancement through increased activation pathways. For example, enhanced the TNFα–TNFR1-NF-κB-glutaminase-GAT3 pathway TNFα-TNFR1-S1PR2-CCL2-BDNF-TrkB cerebellum hyperammonemic rats enhances neurotransmission. This mediated by mechanisms affecting GABA synthesizing...
Abstract The aim of this work was to assess whether ammonia concentrations similar the increase found in brain hyperammonemic rats (100 μ m ), impair N ‐methyl‐ d ‐aspartate (NMDA) receptor‐mediated signal transduction. We first measured glutamate neurotoxicity, which these neurons is mediated by activation NMDA receptors, as an initial parameter reflecting pathways. Long‐term treatment cultured with prevents glutamate‐induced neuronal death. EC 50 20 , and at 100 protection complete....
Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate impairment. Taking into account these data, we hypothesized that rats HE: 1) is a main contributor neuroinflammation; 2) hippocampus impairs spatial learning altering AMPA and/or NMDA receptors membrane expression; 3) reducing infliximab...
There are no specific treatments for the neurological alterations of cirrhotic patients with minimal hepatic encephalopathy (MHE). Rats MHE due to portacaval shunt (PCS) show impaired spatial learning. The underlying mechanisms remain unknown. aims this work were assess: (a) whether PCS rats neuroinflammation in hippocampus, (b) treatment sildenafil reduces and restores learning rats, (c) analyze mechanisms. Neuroinflammation was assessed by determining inflammatory markers Western blot....
Peripheral inflammation contributes to the neurological alterations in hepatic encephalopathy (HE). Neuroinflammation and altered GABAergic neurotransmission mediate cognitive motor rats with HE. It remains unclear (a) if neuroinflammation impairment HE are a consequence of peripheral (b) how impairs neurotransmission. The aims were assess whether reducing anti-TNF-α (1) prevents in-coordination, (2) normalizes extracellular GABA cerebellum also (3) advances understanding mechanisms linking...
In tests of spatial ability, males outperform females both in rats and humans. The mechanism underlying this gender differential learning ability memory tasks remains unknown. Long-term potentiation (LTP) the hippocampus is considered basis for memory. aims work were (a) to assess male female radial Morris mazes; (b) whether basal synaptic activity LTP are different rats; (c) identify molecular mechanisms responsible differences LTP. We analyzed young performance water hippocampal slices;...
Hepatic encephalopathy (HE) is one of the primary complications liver cirrhosis. Current treatments for HE, mainly directed to reduction ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce neurological alterations. Studies in animal models show that overactivation GABA A receptors involved cognitive motor impairment HE reducing this activation restores these functions. We have developed a new compound, GR3027,...
Abstract Aims Chronic hyperammonaemia and inflammation synergistically induce neurological impairment, including motor incoordination, in hepatic encephalopathy. Hyperammonaemic rats show neuroinflammation the cerebellum which enhances GABAergic neurotransmission leading to incoordination. We aimed identify underlying mechanisms. The aims were (1) assess if S1PR2 is involved microglial astrocytic activation of hyperammonaemic rats; (2) pathways by enhanced induces alters neurotransmission;...
<h3>Objective</h3> Inflammation plays a role in neurological alterations patients with hepatic encephalopathy (HE). Animal models of HE show neuroinflammation. Treatment ibuprofen, non-steroidal anti-inflammatory drug (NSAID), reduces neuroinflammation and restores cognitive motor function rats due to portacaval shunts (PCS). This suggests that reducing would improve status minimal or clinical HE. NSAID induce kidney damage cirrhosis PCS are not suitable for use. It is therefore necessary...
Summary Aims Patients with liver disease may develop hepatic encephalopathy ( HE ), cognitive impairment and motor in‐coordination. Rats due to portacaval shunts PCS ) show We hypothesized that in rats: (i) Motor in‐coordination would be enhanced GABA ergic tone cerebellum; (ii) increased neuroinflammation; (iii) increasing cGMP reduce neuroinflammation restore coordination. To assess these hypotheses, we assessed if treatment sildenafil reduces reduced is associated restored Methods were...
Abstract Background Patients with liver cirrhosis may develop hepatic encephalopathy. Rats chronic hyperammonemia exhibit neurological alterations mediated by peripheral inflammation and neuroinflammation. Motor incoordination is due to increased TNF-a levels activation of its receptor TNFR1 in the cerebellum. The aims were assess (a) whether responsible for induction hyperammonemic rats, (b) cell type(s) which increased, (c) this increase associated nuclear NF-κB activation, (d) time course...