Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Aspects of cAMP Signaling in Epileptogenesis and Seizures and Its Potential as Drug Target

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The Top 5 Neurotransmitters from a Clinical Neurologist's Perspective

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. A matter of balance: role of neurexin and neuroligin at the synapse

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Functional recovery of regenerating motor axons is delayed in mice heterozygously deficient for the myelin protein P(0) gene

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Transcerebral exchange kinetics of large neutral amino acids during acute inspiratory hypoxia in humans

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Artificial liver support in acute and acute-on-chronic liver failure

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Lever- og galdevejssygdomme

    Publikation: Bidrag til bog/antologi/rapportBidrag til bog/antologiFormidling

  4. Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftNeurochemical Research
Vol/bind40
Udgave nummer2
Sider (fra-til)258-64
Antal sider7
ISSN0364-3190
DOI
StatusUdgivet - feb. 2015

ID: 45942422