Effect of the Oral Administration of Branched Chain Amino Acids on Hepatic Encephalopathy in the Rat

Beaubernard, C; Delorme, M. L.; Opolon, P; Boschat, M.; Morin, Jean Paul; Oryszcyn, Marie-Plerre; Franco, Dominique

doi:10.1002/hep.1840040219

Cited by 14 publications

(8 citation statements)

References 25 publications

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“…22 It has been previously shown that after PCA in the rat, both the serotonergic and histaminergic systems show profound disturbances in their function. 9,[11][12][13][14][15]25 The present study reproduces these results, showing that 6 months after PCA surgery, the histamine system in the frontal cortex responds by an increase in the amount of both the amine and metabolite, and the serotonin system by increase only in the level of the metabolite. Importantly, the tissue concentrations of tele-methylhistamine, which reflect the release of histamine into the extracellular space and thus serve as indirect indices of histaminergic activity, 36 are significantly elevated, in agreement with previous reports.…”

Section: Discussionsupporting

confidence: 85%

“…Furthermore, we describe increased levels of both histamine and tele-methylhistamine in the frontal cortex of these rats 6 months after PCA. Combining these results with the findings of significantly increased tissue histamine and tele-methylhistamine levels between 1 and 6 months after PCA, 12,14,15,25 and the observation of significantly increased extracellular levels of histamine, 37 it appears that the altered sleep patterns during the light phase in rats with PCA mirror the changes in the brain histaminergic system. Therefore, we suggest that, in addition to other factors, histamine may play a role in the development of sleep disturbances in rats with PCA.…”

Section: Discussionsupporting

confidence: 53%

“…PCA, 12,14,15,25 and the observation of significantly increased extracellular levels of histamine, 37 it appears that the altered sleep patterns during the light phase in rats with PCA mirror the changes in the brain histaminergic system. Therefore, we suggest that, in addition to other factors, histamine may play a role in the development of sleep disturbances in rats with PCA.…”

Section: Fig 4 (A)mentioning

confidence: 94%

“…23,24 Furthermore, earlier studies have demonstrated a correlation between the sleep disturbances and brain histamine levels in rats with PCA. 21,25 Because histamine has a well-known physiological role in the modulation of sleep behavior and circadian rhythms, we have now attempted to find out whether the increased brain levels of histamine in PCA-operated rats are associated with changes in the sleep patterns of these rats during the light phase. Because such changes cannot be detected by simple observation, we used electroencephalographic (EEG) recordings from the frontal cortex of freely behaving rats as brain-state markers to discriminate sleep, drowsiness, and wakefulness.…”

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confidence: 99%

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Brain histamine levels and neocortical slow-wave activity in rats with portacaval anastomosis

et al. 1999

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To determine whether the increased histamine levels in the brain of rats with portacaval anastomosis (PCA) are associated with the development of sleep disturbances during the light phase, the neocortical slow-wave activity of PCA-operated rats was examined with electroencephalography (EEG) 1 month and 6 months after the surgery. The tissue levels of histamine, tele-methylhistamine, 5-hydroxytryptamine (5-HT) (serotonin), and 5-hydroxyindole-3-acetic acid (5-HIAA) in frontal cortex were assayed by high-performance liquid chromatography 6 months after the surgery. PCA surgery led to changes in the synchronized, low-frequency, high-amplitude frontal cortex EEG activity recorded during the light phase. Delta-wave amplitude but not delta time was significantly decreased, whereas both spindle amplitude and spindling time were significantly decreased. There were also significant age-related changes, presented as increases in the duration of spindles and the amplitude of both delta waves and spindles. PCA-operated rats showed a change in the pattern of EEG activity with increasing age similar to sham-operated rats. This suggests that once established, the resetting of the systems regulating the sleep-waking behavior is being maintained with time. The tissue levels of both histamine and metabolite in the frontal cortex were increased, whereas the serotonin system showed only an increase in the level of the metabolite. There was a significant negative correlation between the spindling time and the tissue histamine levels. We suggest that histamine, which participates in the control of vigilance, sleep, and wakefulness, as well as in the modulation of circadian rhythmicity, may play a role in the development of sleep disturbances in rats with PCA. (HEPATOLOGY 1999;29:340-346.)Portal-systemic encephalopathy (PSE) is a potential longterm complication in any patient with chronic liver disease receiving a portacaval shunt. The biochemical changes that occur in the plasma and brain of patients with PSE can be reproduced in the rat with portacaval anastomosis (PCA). 1 The clinical presentation of PSE at early stages is dominated by the diminished total duration of slow-wave sleep, the disorganization of the normal nocturnal sleep cycles, the reversed sleep patterns, and the decrease in the spontaneous voluntary movement. Moreover, according to a recent study, approximately half of the cirrhotic patients without overt encephalopathy complain of sleep disturbances. 2 The neurological changes that are consequences of a portacaval shunt in the rat are also manifested as disruptions of sleep patterns and diurnal rhythms, changes in the vigilance or motor activity, and neuromuscular coordination. [3][4][5][6][7][8][9][10] Although much research has been performed to reveal the pathogenesis of PSE, the exact mechanisms responsible for the generation and maintenance of the sleep disturbances are still unclear. Until now, they have been attributed mainly to modification of serotonergic neurotransmission. 9,11 One of the most striking co...

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 53%

Section: Fig 4 (A)mentioning

confidence: 94%

mentioning

confidence: 99%

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Brain histamine levels and neocortical slow-wave activity in rats with portacaval anastomosis

et al. 1999

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“…Recent studies have demonstrated that branched-chain amino acid supplementation of the diet i l l ) and blood gavage (12) do not appear to modify behavior. However, in an earlier report, branched-chain amino acid supplementation of the diet appeared to reduce behavioral changes (13). Recently implantation of hepatocytes into the spleen of t.he PCS rat was reported to increase SMA (14).…”

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confidence: 90%

Gender-dependent reduction of spontaneous motor activity and growth in rats subjected to portacaval shunt

Conjeevaram

1994

Hepatology

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Alterations in behavior are frequently described in rats subjected to portacaval shunt. Previous work has reported reduced spontaneous motor activity in various settings (nighttime, red light, decreased illumination) in this animal model. We investigated this phenomenon in rats of both genders subjected to portacaval shunt to determine whether our previously observed divergent growth patterns (males reduced, females unchanged) had any impact on the alterations in spontaneous motor activity in this model. Dietary intake, growth, motor activity and serum ammonia and amino acid concentrations were measured, in addition to final liver and spleen weights, in each animal after 3 to 4 wk of observation. Our results reconfirm the differential impact of portacaval shunt on growth in male (35% reduction p < 0.01) but not female rats (5% reduction, NS) compared with their respective-gender sham-operated controls. In addition, spontaneous motor activity was significantly reduced in male (congruent to 50%, p = 0.01) but not female rats subjected to portacaval shunt. The reduction of activity in male rats subjected to portacaval shunt did not correlate with any of the measured biochemical data or calculated nutritional/growth parameters. Thus we observed gender-dependent reduction in spontaneous motor activity after portacaval shunt in the rat. The mechanism for this phenomenon is unknown, but it is easily investigated with this reproducible model.

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Central Nervous System and Pulmonary Complications of End‐Stage Liver Disease

Bajaj

2015

Yamada' S Textbook of Gastroenterology

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Effect of the Oral Administration of Branched Chain Amino Acids on Hepatic Encephalopathy in the Rat

Cited by 14 publications

References 25 publications

Brain histamine levels and neocortical slow-wave activity in rats with portacaval anastomosis

Brain histamine levels and neocortical slow-wave activity in rats with portacaval anastomosis

Gender-dependent reduction of spontaneous motor activity and growth in rats subjected to portacaval shunt

Central Nervous System and Pulmonary Complications of End‐Stage Liver Disease

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