Changes in the permeability of the blood-brain barrier in acute hyperammonemia

Ziylan, Y. Ziya; Üzüm, Gülay; Bernard, G.; As, Diler; Jm, Bourre

doi:10.1007/bf03160074

Cited by 22 publications

(9 citation statements)

References 37 publications

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“…A small increase in brain water content was already present in PCS rats and in sham-PCS rats with hyperammonaemia, the latter in agreement with other studies (4,5,10,11,45). Blei et al did not show an increase in brain water content in rats, 1 day after a PCS.…”

Section: Ad 3 Increased Intracranial Pressure and Higher Brain Watersupporting

confidence: 89%

The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy

Vogels¹,

Steynen²,

Maas³

et al. 1997

Journal of Hepatology

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The effects of ammonia and portal-systemic shunting on brain metabolims, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy Vogels, B.A.P.M.; van Steynen, B.; Maas, M.A.W.; Jorning, G.G.A.; Chamuleau, R.A.F.M. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Background/Aims: The pathogenetic factors contributing to encephalopathy in portacaval shunted rats with hyperammonaemia were studied. Methods: Hyperammonaemia was induced by ammonium-acetate infusions in portacaval shunted rats (2.8 mmol-kg bw-'*h-l; AI-portacaval shunted rats) and in sham-portacaval shunted rats (6.5 mmol-kg bw-l-h-'; AI-NORM rats). Severity of encephalopathy was quantified by clinical grading and EEG spectral analysis. Changes in brain metabolites were assessed by amino acid analysis of brain cortex homogenates, whereas changes in amino acids with neurotransmitter activity were assessed in cerebrospinal fluid; brain water content was measured by subtracting dry from wet brain weights and intracranial pressure was measured by a pressure transducer connected to a cisterna magna cannula. Results:Although similar increased blood and brain ammonia concentrations were obtained in both experimental groups, only AI-portacaval shunted rats developed encephalopathy, associated with a significant increase in intracranial pressure. HEPATIC encephalopathy (HE) is generally regarded to be a reversible neuropsychiatric syndrome in patients with liver failure. It is often associated with portal-systemic shunting of blood, which may occur spontaneously or be surgically induced. Although the pathogenesis of HE is probably multi- Conclusions: These results indicate that hyperammonaemia alone does not induce encephalopathy, whereas portal-systemic shunting adds an essential contribution to the pathogenesis of encephalopathy. It is hypothesised that the larger increase in brain glutamine in AI-portacaval shunted rats than in AI-NORM rats is responsible for increased brain concentrations of aromatic amino acids, for cell swelling and for extracellular release of glutamate and aspartate. This might promote encephalopathy. If cell swelling is not restricted, intracranial hypertension will develop

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Section: Ad 3 Increased Intracranial Pressure and Higher Brain Watersupporting

confidence: 89%

The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy

Vogels¹,

Steynen²,

Maas³

et al. 1997

Journal of Hepatology

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“…The enzymatic degradation of urea produces ammonia. Ammonia is highly toxic to brain endothelium as seen in inborn errors of metabolism involving the urea acid cycle and in Reye syndrome, in which there is an accumulation of ammonia (33,34). Similarly, ammonia produced by urease is toxic to gastric epithelium during Helicobacter pylori infection (35).…”

Section: Discussionmentioning

confidence: 99%

Real-time imaging of trapping and urease-dependent transmigration of Cryptococcus neoformans in mouse brain

Shi¹,

Li²,

Zheng³

et al. 2010

J. Clin. Invest.

187

259

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Infectious meningitis and encephalitis is caused by invasion of circulating pathogens into the brain. It is unknown how the circulating pathogens dynamically interact with brain endothelium under shear stress, leading to invasion into the brain. Here, using intravital microscopy, we have shown that Cryptococcus neoformans, a yeast pathogen that causes meningoencephalitis, stops suddenly in mouse brain capillaries of a similar or smaller diameter than the organism, in the same manner and with the same kinetics as polystyrene microspheres, without rolling and tethering to the endothelial surface. Trapping of the yeast pathogen in the mouse brain was not affected by viability or known virulence factors. After stopping in the brain, C. neoformans was seen to cross the capillary wall in real time. In contrast to trapping, viability, but not replication, was essential for the organism to cross the brain microvasculature. Using a knockout strain of C. neoformans, we demonstrated that transmigration into the mouse brain is urease dependent. To determine whether this could be amenable to therapy, we used the urease inhibitor flurofamide. Flurofamide ameliorated infection of the mouse brain by reducing transmigration into the brain. Together, these results suggest that C. neoformans is mechanically trapped in the brain capillary, which may not be amenable to pharmacotherapy, but actively transmigrates to the brain parenchyma with contributions from urease, suggesting that a therapeutic strategy aimed at inhibiting this enzyme could help prevent meningitis and encephalitis caused by C. neoformans infection.

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“…A plausible explanation for the development of diffuse extracellular edema is increased blood-brain barrier permeability in particularly vulnerable areas, probably induced by age-related microvascular changes. In fact, hyperammonemia may induce an increase in blood-brain barrier permeability, 28,29 which would favor capillary water influx to the brain. Moreover, Alzheimer type II astrocytes, a common abnormality in HE that has been interpreted as a sign of astrocyte swelling, may indeed correspond to cellular damage and loss of cellular shape caused by oxidative stress, rather than intracellular edema.…”

Section: Discussionmentioning

confidence: 99%

Decreased white matter lesion volume and improved cognitive function after liver transplantation

et al. 2007

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Focal T2-weighted white matter lesions (WML) on brain magnetic resonance imaging (MRI), mimicking those seen in cerebrovascular small-vessel disease described in patients with persistent hepatic encephalopathy, decreased in volume with the improvement of hepatic encephalopathy. This outcome has been interpreted as a decrease in the edema that it is proposed to be involved in the pathogenesis of hepatic encephalopathy. We designed a study to further investigate potential changes in focal WML in the brains of patients with cirrhosis following liver transplantation and to study the relationship between these changes and overall cognitive function. We used MRI to measure the volume of supratentorial focal WML and a neuropsychological examination to assess cognitive function before and after liver transplantation in 27 patients with cirrhosis without signs of overt hepatic encephalopathy. Baseline MRI identified focal T2-weighted lesions in 19 patients (70.3%). The presence of WML was associated with older age but not with vascular risk factors, severity of liver function, or psychometric tests. A significant reduction in lesion volume was observed after liver transplantation (from a median of 1.306 cm 3 to 0.671 cm 3 , P ‫؍‬ 0.001). This decrease correlated with an improvement in an index of global cognitive function (r ‫؍‬ ؊0.663; P < 0.001). This evolution indicates that lesion volume is partially related to a reversible type of tissue damage, which is compatible with brain edema. F ocal white matter lesions (WML) secondary to cerebrovascular small-vessel disease are commonly found in the general population over 60 years of age. 1 In a previous report, we described focal brain WML on T2-weighted images in patients with hepatic encephalopathy (HE). 2 This abnormality, which is radiologically indistinguishable from the features of small-vessel disease or normal aging, was partially reversible with improvements in HE. This evolution pattern contrasts with what occurs in focal WML attributable to small-vessel disease or brain aging, which remain stable or progress in number and size over time, but never decrease. [3][4][5] The most plausible explanation for decreasing the volume of WML with improvement of HE is a decrease in the edema component of WML.There is a large body of evidence indicating an increase in the amount of water in the brain of patients with liver cirrhosis that is related to the development of HE. 6 The most accepted hypothesis for this low-grade brain edema is that astrocytic accumulation of glutamine induces edema as a result of ammonia detoxification. This hypothesis is supported by experimental data showing astrocyte swelling and changes in brain organic osmolytes in models of HE, 7 and by brain proton magnetic resonance spectroscopy studies in patients with liver cirrhosis, which consistently show increases in the glutamine/glutamate signal accompanied by myoinositol depletion, 8

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Changes in the permeability of the blood-brain barrier in acute hyperammonemia

Cited by 22 publications

References 37 publications

The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy

The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy

Real-time imaging of trapping and urease-dependent transmigration of Cryptococcus neoformans in mouse brain

Decreased white matter lesion volume and improved cognitive function after liver transplantation

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