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Profiling of astrocyte properties in the hyperammonaemic brain: Shedding new light on the pathophysiology of the brain damage in hyperammonaemia

  • Original Article
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Journal of Inherited Metabolic Disease

Summary

Acute hyperammonaemia (HA) causes cerebral oedema and severe brain damage in patients with urea cycle disorders (UCDs) or acute liver failure (ALF). Chronic HA is associated with developmental delay and intellectual disability in patients with UCDs and with neuropsychiatric symptoms in patients with chronic liver failure. Treatment often cannot prevent severe brain injury and neurological sequelae. The causes of the brain oedema in hyperammonaemic encephalopathy (HAE) have been subject of intense controversy among physicians and scientists working in this field. Currently favoured hypotheses are astrocyte swelling due to increased intracellular glutamine content and neuronal cell death due to excitotoxicity caused by elevated extracellular glutamate levels. While many researchers focus on these mechanisms of cytotoxicity, others emphasize vascular causes of brain oedema. New data gleaned from expression profiling of astrocytes acutely isolated from hyperammonaemic mouse brains point to disturbed water and potassium homeostasis as regulated by astrocytes at the brain microvasculature and in the perisynaptic space as a potential mechanism of brain oedema development in hyperammonaemia.

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Authors and Affiliations

  1. Center for Neuroscience Research, Washington, DC, USA

    U. Lichter-Konecki

  2. Division of Genetics & Metabolism, Children’s National Medical Center, 111 Michigan Ave., NW, Washington, DC, 20010-2970, USA

    U. Lichter-Konecki

  3. Department of Pediatrics, George Washington University Medical Center, Washington, DC, USA

    U. Lichter-Konecki

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  1. U. Lichter-Konecki
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Correspondence to U. Lichter-Konecki.

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Communicating editor: Verena Peters

Competing interests: None declared

References to electronic databases: Ornithine transcarbamylase deficiency: OMIM 311250. Ornithine transcarbamylase: EC 2.1.3.3.

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Lichter-Konecki, U. Profiling of astrocyte properties in the hyperammonaemic brain: Shedding new light on the pathophysiology of the brain damage in hyperammonaemia. J Inherit Metab Dis 31, 492–502 (2008). https://doi.org/10.1007/s10545-008-0834-9

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