Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747066
Title: Neurochemistry of the hepatic encephalopathy
Author: Hadjihambi, Anna
ISNI:       0000 0004 7228 1745
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Abstract:
The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and the role of ammonia remains controversial. Experimental studies conducted in animal (rat) models of HE, in combination with pharmacological approaches, were used to test the hypothesis that during HE, chronic exposure to elevated ammonia concentrations alters cerebral oxygenation, compromises lactate transport between astrocytes and neurons, and impairs uptake of neurotransmitters. It was also hypothesised that HE impairs glymphatic clearance mechanisms, either as a cause or a consequence of the disease, which exacerbates the detrimental central nervous effects of the accumulated toxins. The results of the experiments described in this thesis suggest that in HE: a) ammonia compromises cerebral oxygenation, but does not affect cerebrovascular reactivity, b) ammonia mediates cortical hemichannel dysfunction and impairs channel-mediated lactate release, potentially interfering with the astrocyte-neuron lactate shuttle, c) hyperammonemia results in a significant increase in cortical extracellular glutamate concentration, which is exacerbated under hypoxic conditions, and d) efficacy of glymphatic clearance is affected in discrete regions of the brain, which aligns with specific cognitive/behavioral impairments. These findings provide the first evidence of a critical pathophysiological role of ammonia in inducing neuronal energy deficit in HE due to impaired cerebral oxygenation, compromised hemichannel-mediated lactate transport between astrocytes and neurons and affected glymphatic clearance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.747066  DOI: Not available
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