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Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats: a biosensor study

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@article{5689f8106e414f15ac7870231282487c,
title = "Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats: a biosensor study",
abstract = "Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18 µM in brain slices. In vivo recordings showed a tendency towards increased adenosine levels in rats with hyperammonemia and systemic inflammation compared to a control group (3.7 ± 0.7 vs. 0.8 ± 0.2 µM, P = 0.06). This was associated with a significant increase in ICP and CBF. Intervention with the non-selective adenosine receptor antagonist theophyllamine, the A2A receptor antagonist ZM241385, or the A1 receptor agonist N6-Cyclopentyladenosine did not reduce ICP or CBF. In conclusion, our results show that the adenosine concentration in cortex increases during exposure to ammonia, and is associated with a rise in intracranial pressure and cerebral perfusion. However adenosine receptor antagonism/agonism did not reduce the ICP or CBF which indicates that adenosine may not be of direct importance for these cerebral complications in ALF.",
keywords = "Adenosine, Animals, Biosensing Techniques, Brain, Extracellular Space, Hyperammonemia, Inflammation, Male, Rats, Rats, Wistar",
author = "Bjerring, {Peter Nissen} and Nicholas Dale and Larsen, {Fin Stolze}",
year = "2015",
month = "2",
doi = "10.1007/s11064-014-1357-4",
language = "English",
volume = "40",
pages = "258--64",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer New York LLC",
number = "2",

}

RIS

TY - JOUR

T1 - Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

T2 - a biosensor study

AU - Bjerring, Peter Nissen

AU - Dale, Nicholas

AU - Larsen, Fin Stolze

PY - 2015/2

Y1 - 2015/2

N2 - Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18 µM in brain slices. In vivo recordings showed a tendency towards increased adenosine levels in rats with hyperammonemia and systemic inflammation compared to a control group (3.7 ± 0.7 vs. 0.8 ± 0.2 µM, P = 0.06). This was associated with a significant increase in ICP and CBF. Intervention with the non-selective adenosine receptor antagonist theophyllamine, the A2A receptor antagonist ZM241385, or the A1 receptor agonist N6-Cyclopentyladenosine did not reduce ICP or CBF. In conclusion, our results show that the adenosine concentration in cortex increases during exposure to ammonia, and is associated with a rise in intracranial pressure and cerebral perfusion. However adenosine receptor antagonism/agonism did not reduce the ICP or CBF which indicates that adenosine may not be of direct importance for these cerebral complications in ALF.

AB - Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18 µM in brain slices. In vivo recordings showed a tendency towards increased adenosine levels in rats with hyperammonemia and systemic inflammation compared to a control group (3.7 ± 0.7 vs. 0.8 ± 0.2 µM, P = 0.06). This was associated with a significant increase in ICP and CBF. Intervention with the non-selective adenosine receptor antagonist theophyllamine, the A2A receptor antagonist ZM241385, or the A1 receptor agonist N6-Cyclopentyladenosine did not reduce ICP or CBF. In conclusion, our results show that the adenosine concentration in cortex increases during exposure to ammonia, and is associated with a rise in intracranial pressure and cerebral perfusion. However adenosine receptor antagonism/agonism did not reduce the ICP or CBF which indicates that adenosine may not be of direct importance for these cerebral complications in ALF.

KW - Adenosine

KW - Animals

KW - Biosensing Techniques

KW - Brain

KW - Extracellular Space

KW - Hyperammonemia

KW - Inflammation

KW - Male

KW - Rats

KW - Rats, Wistar

U2 - 10.1007/s11064-014-1357-4

DO - 10.1007/s11064-014-1357-4

M3 - Journal article

VL - 40

SP - 258

EP - 264

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 2

ER -

ID: 45942422