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| 1 | Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests显示文摘AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow(BF) was analyzed by arterial spin labeling(ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy(MHE). Images were collected using a 3 Tesla MR scanner(Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score(PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins(IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated.RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere(P = 0.03) and vermis(P = 0.012) and reduced in occipital lobe(P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE(P = 0.02). Bimanual coordination was impaired in patients without MHE(P = 0.05) and much more in patients with MHE(P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE(P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE(P< 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A(NCT-A), B(NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with CFF. BF in cerebellar hemisphere correlates with plasma cGMP and nitric oxide(NO) metabolites. BF in vermis cerebellar also correlates with NO metabolites and with 3-nitrotyrosine. IL-18 in plasma correlates with BF in thalamus and occipital lobe.CONCLUSION: Non invasive BF determination in cerebellum using ASL may detect MHE earlier than the PHES. Altered NO-cGMP pathway seems to be associated to altered BF in cerebellum. | Vicente Felipo Amparo Urios Carla Giménez-Garzó Omar Cauli Maria-Jesús Andrés-Costa Olga González Miguel A Serra Javier Sánchez-González Roberto Aliaga Remedios Giner-Durán Vicente Belloch Carmina Montoliu | 2014 | World Journal of Gastroenterology2014，20，33： | 12 |
| 2 | Contribution of altered signal transduction associated to glutamate receptors in brain to the neurological alterations of hepatic encephalopathy显示文摘Patients with liver disease may present hepatic enceph- alopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations, including cognitive and motor disturbances. HE reduces the quality of life of the patients and is associated with poor prognosis. In the worse cases HE may lead to coma or death. The mechanisms leading to HE which are not well known are being studied using animal models. The neurological alterations in HE are a consequence of impaired cerebral function mainly due to alterations in neurotransmission. We review here some studies indicating that alterations in neurotransmission associated to different types of glutamate receptors are responsible for some of the cognitive and motor alterations present in HE. These studies show that the function of the signal transduction pathway glutamate-nitric oxide-cGMP associated to the NMDA type of glutamate receptors is impaired in brain in vivo in HE animal models as well as in brain of patients died of HE. Activation of NMDA receptors in brain activates this pathway and increases cGMP. In animal models of HE this increase in cGMP induced by activation of NMDA receptors is reduced, which is responsible for the impairment in learning ability in these animal models. Increasing cGMP by pharmacological means restores learning ability in rats with HE and may be a new therapeutic approach to improve cognitive function in patients with HE. However, it is necessary to previously assess the possible secondary effects.Patients with HE may present psychomotor slowing, hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It has been shown in rats with HE that hypolocomotion is due to excessive activation of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata. Blocking mGluR1 in this brain area normalizes motor activity in the rats, suggesting that a similar treatment for patients with HE could be useful to treat psychomotor slowing and hypokinesia. However, the possible secondary effects of mGluR1 antagonists should be previously evaluated. These studies are setting the basis for designing therapeutic procedures to specifically treat the individual neurological alterations in patients with HE. | Vicente Felipo | 2006 | World Journal of Gastroenterology2006，12，48： | 2 |
| 3 | Mitochondrial dysfunction in acute hyperammonemia 显示文摘 | FELIPO V BUTTERWORTH RF | 2002 | Neuroche M Int2002，40，6： | 1 |
| 4 | Contribution of hyperam- monemia and inflammatory factors to cognitive impairment in mini- mal hepatic encephalopathy 显示文摘 | Felipo V Urios A Montesinos E | 2012 | Metab Brain Dis2012，27，1： | 1 |
| 5 | Brain Region-Selective Mechanisms Contribute to the Progression of Cerebral Alterations in Acute Liver Failure in Rats显示文摘 | Omar Cauli Pilar López–Larrubia Regina Rodrigo Ana Agusti Jordi Boix Laura Nieto–Charques Sebastián Cerdán Vicente Felipo | 2011 | Gastroenterology2011，，2： | 1 |
| 6 | Nitrogen mineralization in soil amended with sewage and fly ash 显示文摘 | Garau M A Dalmau J L Felipo M T | 1991 | Water Sci Tech1991，12，： | 1 |
| 7 | Insight into the neuropro- teomics effects of the food - contaminant non - dioxin like polych|o- rinated biphenyls 显示文摘 | Brunelli L Llansola M Felipo V | 2012 | J Proteomics2012，75，8： | 1 |
| 8 | Hepatic encephalopathy : effects of liver failure on brain function显示文摘 | Felipo Y | 2013 | Nat Rev Nettmsci2013，14，12： | 1 |
| 9 | Hyperammonemia alters the modulation by different neurosteroids of the glutamate–nitric oxide–cyclic GMP pathway through NMDA‐ GABA<sub>A</sub>‐ or sigma receptors in cerebellum in vivo显示文摘 | Alba González‐Usano Omar Cauli Ana Agustí Vicente Felipo | 2013 | J Neurochem2013，，1： | 1 |
| 10 | Sources of oxygen radicals in brain in acute ammonia intoxication in vivo显示文摘 | Elena Kosenko Natalia Venediktova Yury Kaminsky Carmina Montoliu Vicente Felipo | 2003 | Brain Research2003，，1： | 1 |
| 11 | Control of brain glutamine synthesis by NMDA reeept ors显示文摘 | Rodrigo R Felipo V | 2007 | Front Biosci2007，1，12： | 1 |
| 12 | Ammonia prevents activation of NMDA receptors by glutamate in rat cerebellar neuronal cultures 显示文摘 | Marcaida G MiSana MD Burgal M Grisolfa S Felipo V | 1995 | Eur J Neurosci1995，7，12： | 1 |
| 13 | Neurobiology of ammonia显示文摘 | Vicente Felipo Roger F. Butterworth | 2002 | Progress in Neurobiology2002，，4： | 1 |
| 14 | Benign adenomyoep-ithelioma of the breast: a case with gross mimicking of malignancy 显示文摘 | Felipo F Del Agua C Eguizabal C Vaquero M | 2002 | Breast J2002，，8： | 1 |
| 15 | Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration显示文摘 | Felipo F Vaquero M del Agua C | 2004 | J Cutan Pathol2004，31，8： | 1 |
| 16 | Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms显示文摘 | Sdnchez-Perez AM Felipo V | 2005 | Neurochem Int2005，47，12： | 1 |
| 17 | Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts显示文摘 | Cauli O Rodrigo R Piedrafita B Boix J Felipo V | 2007 | Hepatology2007，46，： | 1 |
| 18 | Epithelial-myoepithelial turnout of the lung:a case report referring to its molecular histogene-sis显示文摘 | Munoz G Felipo F Marquina I | 2011 | Diagn Pathol2011，6，： | 1 |
| 19 | Molecular mechanism of acute ammonia toxicity and of its prevention by 1-carnatine显示文摘 | Felipo V Kosenko E Minana MD | 1994 | Adv Exp Med Biol1994，368，： | 1 |
| 20 | Molecular Mechanisms of the Alterations in NMDA Receptor-Dependent Long-Term Potentiation in Hyperammonemia显示文摘 | Pilar Monfort María-Dolores Mu?oz Vicente Felipo | 2005 | Metabolic Brain Disease2005，，4： | 1 |
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