Ammonia toxicity to the brain

Braissant, Olivier; Mclin, Valérie Anne; Cudalbu, Cristina

doi:10.1007/s10545-012-9546-2

Scientific article

Review

English

Ammonia toxicity to the brain

Contributors

Braissant, Olivier; Mclin, Valérie Anne; Cudalbu, Cristina

Published in

Journal of inherited metabolic disease, vol. 36, no. 4, p. 595-612

Publication date

2013

Abstract

Hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle defects. The brain is much more susceptible to the deleterious effects of ammonium in childhood than in adulthood. Hyperammonemia provokes irreversible damage to the developing central nervous system: cortical atrophy, ventricular enlargement and demyelination lead to cognitive impairment, seizures and cerebral palsy. The mechanisms leading to these severe brain lesions are still not well understood, but recent studies show that ammonium exposure alters several amino acid pathways and neurotransmitter systems, cerebral energy metabolism, nitric oxide synthesis, oxidative stress and signal transduction pathways. All in all, at the cellular level, these are associated with alterations in neuronal differentiation and patterns of cell death. Recent advances in imaging techniques are increasing our understanding of these processes through detailed in vivo longitudinal analysis of neurobiochemical changes associated with hyperammonemia. Further, several potential neuroprotective strategies have been put forward recently, including the use of NMDA receptor antagonists, nitric oxide inhibitors, creatine, acetyl-L-carnitine, CNTF or inhibitors of MAPKs and glutamine synthetase. Magnetic resonance imaging and spectroscopy will ultimately be a powerful tool to measure the effects of these neuroprotective approaches.

UNIGE affiliation entities

Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

UNIGE research groups

Pathologies hépatiques congénitales et acquises de l'enfant (900)

Citation (ISO format)

BRAISSANT, Olivier, MCLIN, Valérie Anne, CUDALBU, Cristina. Ammonia toxicity to the brain. In: Journal of inherited metabolic disease, 2013, vol. 36, n° 4, p. 595–612. doi: 10.1007/s10545-012-9546-2

Article (Published version)

Identifiers

PID : unige:35588
DOI : 10.1007/s10545-012-9546-2
PMID : 23109059

Journal ISSN

0141-8955

624views

2downloads

Creation

27/02/2014 13:44:00

First validation

27/02/2014 13:44:00

Update

19/09/2025 10:15:42

Status update

19/09/2025 10:15:42

Last indexation

19/09/2025 10:19:42

Ammonia toxicity to the brain

Contributors

Published in

Publication date

Abstract

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

Main files (1)

Identifiers

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation