{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:51:34Z","timestamp":1784249494286,"version":"3.55.0"},"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2018,9,10]],"date-time":"2018-09-10T00:00:00Z","timestamp":1536537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0203707","type":"journal-article","created":{"date-parts":[[2018,9,10]],"date-time":"2018-09-10T17:27:48Z","timestamp":1536600468000},"page":"e0203707","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Pharmacologic rescue of hyperammonemia-induced toxicity in zebrafish by inhibition of ornithine aminotransferase"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9653-2914","authenticated-orcid":true,"given":"Matthias","family":"Zielonka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Breuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen G\u00fcnther","family":"Okun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Carl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg Friedrich","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,9,10]]},"reference":[{"key":"ref1","first-page":"379","article-title":"The Physiology of Fishes","author":"C Wood","year":"1993"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1750-1172-7-32","article-title":"Suggested guidelines for the diagnosis and management of urea cycle disorders","volume":"7","author":"J Haberle","year":"2012","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13023-017-0661-x","article-title":"Incidence, disease onset and short-term outcome in urea cycle disorders -cross-border surveillance in Germany, Austria and Switzerland","volume":"12","author":"S Nettesheim","year":"2017","journal-title":"Orphanet J Rare Dis"},{"issue":"1\u20132","key":"ref4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ymgme.2013.07.008","article-title":"The incidence of urea cycle disorders","volume":"110","author":"ML Summar","year":"2013","journal-title":"Mol Genet Metab"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jpeds.2012.06.065","article-title":"Urea Cycle Disorders Consortium of the Rare Diseases Clinical Research N. Clinical outcomes of neonatal onset proximal versus distal urea cycle disorders do not differ","volume":"162","author":"N Ah Mew","year":"2013","journal-title":"J Pediatr"},{"issue":"6","key":"ref6","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s00431-003-1188-9","article-title":"Outcome and survival of 88 patients with urea cycle disorders: a retrospective evaluation","volume":"162","author":"C Bachmann","year":"2003","journal-title":"Eur J Pediatr"},{"issue":"2","key":"ref7","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s10545-015-9901-1","article-title":"Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders\u2014review and meta-analysis of observational studies published over more than 35 years","volume":"39","author":"P Burgard","year":"2016","journal-title":"J Inherit Metab Dis"},{"issue":"22","key":"ref8","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1056\/NEJMoa066596","article-title":"Survival after treatment with phenylacetate and benzoate for urea-cycle disorders","volume":"356","author":"GM Enns","year":"2007","journal-title":"N Engl J Med"},{"issue":"6","key":"ref9","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s10545-015-9839-3","article-title":"The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation","volume":"38","author":"S Kolker","year":"2015","journal-title":"J Inherit Metab Dis"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/j.1651-2227.2008.00952.x","article-title":"Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes","volume":"97","author":"ML Summar","year":"2008","journal-title":"Acta Paediatr"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13023-016-0493-0","article-title":"Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001\u20132013","volume":"11","author":"C Unsinn","year":"2016","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"ref12","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ajhg.2014.01.006","article-title":"Mitochondrial carbonic anhydrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood","volume":"94","author":"CD van Karnebeek","year":"2014","journal-title":"Am J Hum Genet"},{"issue":"1","key":"ref13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13023-016-0513-0","article-title":"Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study","volume":"11","author":"MC Husson","year":"2016","journal-title":"Orphanet J Rare Dis"},{"issue":"4","key":"ref14","doi-asserted-by":"crossref","first-page":"e523","DOI":"10.1542\/peds.2004-0198","article-title":"Developmental outcomes with early orthotopic liver transplantation for infants with neonatal-onset urea cycle defects and a female patient with late-onset ornithine transcarbamylase deficiency","volume":"114","author":"KL McBride","year":"2004","journal-title":"Pediatrics"},{"issue":"11","key":"ref15","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1002\/lt.20587","article-title":"Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University","volume":"11","author":"D Morioka","year":"2005","journal-title":"Liver Transpl"},{"issue":"5","key":"ref16","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s10545-016-9938-9","article-title":"Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders","volume":"39","author":"R Posset","year":"2016","journal-title":"J Inherit Metab Dis"},{"issue":"7","key":"ref17","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1111\/j.1476-5381.2010.00872.x","article-title":"Group NCRRGW. Animal research: reporting in vivo experiments: the ARRIVE guidelines","volume":"160","author":"C Kilkenny","year":"2010","journal-title":"Br J Pharmacol"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"CB Kimmel","year":"1995","journal-title":"Dev Dyn"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nprot.2007.514","article-title":"High-resolution in situ hybridization to whole-mount zebrafish embryos","volume":"3","author":"C Thisse","year":"2008","journal-title":"Nat Protoc"},{"issue":"11","key":"ref20","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1016\/S0021-9258(19)45190-9","article-title":"The binding of detergents to lipophilic and hydrophilic proteins","volume":"247","author":"A Helenius","year":"1972","journal-title":"J Biol Chem"},{"issue":"1","key":"ref21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"OH Lowry","year":"1951","journal-title":"J Biol Chem"},{"issue":"3","key":"ref22","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The glutamate\/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer","volume":"98","author":"LK Bak","year":"2006","journal-title":"J Neurochem"},{"issue":"4","key":"ref23","doi-asserted-by":"crossref","first-page":"e95855","DOI":"10.1371\/journal.pone.0095855","article-title":"Acute liver failure in rats activates glutamine-glutamate cycle but declines antioxidant enzymes to induce oxidative stress in cerebral cortex and cerebellum","volume":"9","author":"S Singh","year":"2014","journal-title":"PLoS One"},{"issue":"3\u20134","key":"ref24","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cbpb.2012.06.003","article-title":"Glutamine synthetase activity and the expression of three glul paralogues in zebrafish during transport","volume":"163","author":"AK Dhanasiri","year":"2012","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"issue":"6","key":"ref25","doi-asserted-by":"crossref","first-page":"712","DOI":"10.7150\/ijbs.11827","article-title":"Induction of Phosphoenolpyruvate Carboxykinase (PEPCK) during Acute Acidosis and Its Role in Acid Secretion by V-ATPase-Expressing Ionocytes","volume":"11","author":"F Furukawa","year":"2015","journal-title":"Int J Biol Sci"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/hep.28852","article-title":"Pivotal role of glutamine synthetase in ammonia detoxification","volume":"65","author":"TB Hakvoort","year":"2017","journal-title":"Hepatology"},{"issue":"1","key":"ref27","first-page":"133","article-title":"Developmental study of hepatic glutamine synthetase in a mouse model of congenital hyperammonemia","volume":"43","author":"A Skarpetas","year":"1997","journal-title":"Biochem Mol Biol Int"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"13160","DOI":"10.1038\/srep13160","article-title":"Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor","volume":"5","author":"AC Mirando","year":"2015","journal-title":"Sci Rep"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1471-2164-7-20","article-title":"Many genes in fish have species-specific asymmetric rates of molecular evolution","volume":"7","author":"D Steinke","year":"2006","journal-title":"BMC Genomics"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0074-7742(08)60208-1","article-title":"Aminotransferase activity in brain","volume":"17","author":"M Benuck","year":"1975","journal-title":"Int Rev Neurobiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0016-5085(64)80011-1","article-title":"Serum Enzymes in the Diagnosis of Hepatic Disease","volume":"46","author":"HJ Zimmerman","year":"1964","journal-title":"Gastroenterology"},{"issue":"8","key":"ref32","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1111\/j.1460-9568.2011.07628.x","article-title":"Molecular basis of NMDA receptor functional diversity","volume":"33","author":"P Paoletti","year":"2011","journal-title":"Eur J Neurosci"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/dvdy.20532","article-title":"Molecular characterization and embryonic expression of the family of N-methyl-D-aspartate receptor subunit genes in the zebrafish","volume":"234","author":"JA Cox","year":"2005","journal-title":"Dev Dyn"},{"issue":"2","key":"ref34","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1042\/bj2530481","article-title":"5-Fluoromethylornithine, an irreversible and specific inhibitor of L-ornithine:2-oxo-acid aminotransferase","volume":"253","author":"G Daune","year":"1988","journal-title":"Biochem J"},{"issue":"5","key":"ref35","doi-asserted-by":"crossref","first-page":"F994","DOI":"10.1152\/ajprenal.90656.2008","article-title":"Nitrogen excretion in developing zebrafish (Danio rerio): a role for Rh proteins and urea transporters","volume":"296","author":"MH Braun","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"issue":"11","key":"ref36","doi-asserted-by":"crossref","first-page":"R991","DOI":"10.1152\/ajpregu.00411.2012","article-title":"Ontogeny of ornithine-urea cycle gene expression in zebrafish (Danio rerio)","volume":"304","author":"CM LeMoine","year":"2013","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"6","key":"ref37","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s00294-006-0062-5","article-title":"Structural involvement in substrate recognition of an essential aspartate residue conserved in Mep\/Amt and Rh-type ammonium transporters","volume":"49","author":"AM Marini","year":"2006","journal-title":"Curr Genet"},{"issue":"1\u20132","key":"ref38","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ymgme.2014.07.001","article-title":"A zebrafish model of hyperammonemia","volume":"113","author":"B Feldman","year":"2014","journal-title":"Mol Genet Metab"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/0006-291X(92)90653-3","article-title":"Effects of congenital hyperammonemia on the cerebral and hepatic levels of the intermediates of energy metabolism in spf mice","volume":"184","author":"L Ratnakumari","year":"1992","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"ref40","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0304-3940(96)12975-X","article-title":"Arginine-related guanidino compounds and nitric oxide synthase in the brain of ornithine transcarbamylase deficient spf mutant mouse: effect of metabolic arginine deficiency","volume":"215","author":"L Ratnakumari","year":"1996","journal-title":"Neurosci Lett"},{"issue":"12","key":"ref41","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1002\/jnr.22708","article-title":"Interaction between cytokines and ammonia in the mitochondrial permeability transition in cultured astrocytes","volume":"89","author":"VM Alvarez","year":"2011","journal-title":"J Neurosci Res"},{"issue":"5","key":"ref42","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/jnr.10056","article-title":"Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes","volume":"66","author":"G Bai","year":"2001","journal-title":"J Neurosci Res"},{"issue":"Suppl 1","key":"ref43","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1016\/j.ymgme.2003.10.014","article-title":"Ammonia toxicity to the brain and creatine","volume":"81","author":"C Bachmann","year":"2004","journal-title":"Mol Genet Metab"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/0885-4505(87)90102-2","article-title":"Accumulation of large neutral amino acids in the brain of sparse-fur mice at hyperammonemic state","volume":"38","author":"I Inoue","year":"1987","journal-title":"Biochem Med Metab Biol"},{"issue":"1","key":"ref45","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1203\/00006450-199301000-00016","article-title":"Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency","volume":"33","author":"A Connelly","year":"1993","journal-title":"Pediatr Res"},{"issue":"7321","key":"ref46","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature09613","article-title":"Glial and neuronal control of brain blood flow","volume":"468","author":"D Attwell","year":"2010","journal-title":"Nature"},{"key":"ref47","first-page":"179","article-title":"Unraveling the complex metabolic nature of astrocytes","volume":"7","author":"AK Bouzier-Sore","year":"2013","journal-title":"Front Cell Neurosci"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.expneurol.2013.12.024","article-title":"Functional regeneration beyond the glial scar","volume":"253","author":"JM Cregg","year":"2014","journal-title":"Exp Neurol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3389\/fncel.2013.00159","article-title":"How do astrocytes shape synaptic transmission? Insights from electrophysiology","volume":"7","author":"G Dallerac","year":"2013","journal-title":"Front Cell Neurosci"},{"issue":"3","key":"ref50","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/jemt.21061","article-title":"Use of different morphological techniques to analyze the cellular composition of the adult zebrafish optic tectum","volume":"75","author":"CP Corbo","year":"2012","journal-title":"Microsc Res Tech"},{"issue":"21","key":"ref51","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1002\/cne.22481","article-title":"Astroglial structures in the zebrafish brain","volume":"518","author":"L Grupp","year":"2010","journal-title":"J Comp Neurol"},{"issue":"2","key":"ref52","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ydbio.2011.11.001","article-title":"Disruption of Eaat2b, a glutamate transporter, results in abnormal motor behaviors in developing zebrafish","volume":"362","author":"KA McKeown","year":"2012","journal-title":"Dev Biol"},{"issue":"4","key":"ref53","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1172\/JCI103111","article-title":"The cerebral and peripheral uptake of ammonia in liver disease with an hypothesis for the mechanism of hepatic coma","volume":"34","author":"SP Bessman","year":"1955","journal-title":"J Clin Invest"},{"issue":"2","key":"ref54","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1053\/jhep.2003.50052","article-title":"Selective increase of brain lactate synthesis in experimental acute liver failure: results of a [H-C] nuclear magnetic resonance study","volume":"37","author":"C Zwingmann","year":"2003","journal-title":"Hepatology"},{"issue":"1","key":"ref55","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/hep.25995","article-title":"Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake","volume":"57","author":"G Dam","year":"2013","journal-title":"Hepatology"},{"issue":"12","key":"ref56","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.lts.2003.09.020","article-title":"Cerebral glucose and oxygen metabolism in patients with fulminant hepatic failure","volume":"9","author":"GI Strauss","year":"2003","journal-title":"Liver Transpl"},{"issue":"1","key":"ref57","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0031-6997(24)01394-2","article-title":"The glutamate receptor ion channels","volume":"51","author":"R Dingledine","year":"1999","journal-title":"Pharmacol Rev"},{"issue":"11","key":"ref58","first-page":"S7","article-title":"Anatomy and physiology of glutamate in the CNS","volume":"44","author":"JT Greenamyre","year":"1994","journal-title":"Neurology"},{"issue":"Suppl 1","key":"ref59","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.ymgme.2010.02.010","article-title":"Current concepts in the pathogenesis of urea cycle disorders","volume":"100","author":"O Braissant","year":"2010","journal-title":"Mol Genet Metab"},{"issue":"8","key":"ref60","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/0896-6273(88)90162-6","article-title":"Glutamate neurotoxicity and diseases of the nervous system","volume":"1","author":"DW Choi","year":"1988","journal-title":"Neuron"},{"issue":"3880","key":"ref61","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1126\/science.164.3880.719","article-title":"Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate","volume":"164","author":"JW Olney","year":"1969","journal-title":"Science"},{"issue":"3903","key":"ref62","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1126\/science.166.3903.386","article-title":"Brain lesions in an infant rhesus monkey treated with monsodium glutamate","volume":"166","author":"JW Olney","year":"1969","journal-title":"Science"},{"issue":"1\u20133","key":"ref63","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.neuint.2009.01.007","article-title":"Role of NMDA receptors in acute liver failure and ammonia toxicity: therapeutical implications","volume":"55","author":"R Rodrigo","year":"2009","journal-title":"Neurochem Int"},{"issue":"9","key":"ref64","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1056\/NEJM199403033300907","article-title":"Excitatory amino acids as a final common pathway for neurologic disorders","volume":"330","author":"SA Lipton","year":"1994","journal-title":"N Engl J Med"},{"issue":"9","key":"ref65","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0165-6147(90)90184-A","article-title":"Excitatory amino acid neurotoxicity and neurodegenerative disease","volume":"11","author":"B Meldrum","year":"1990","journal-title":"Trends Pharmacol Sci"},{"issue":"3","key":"ref66","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1755-5949.2010.00134.x","article-title":"Dopamine and glutamate in Huntington&apos;s disease: A balancing act","volume":"16","author":"VM Andre","year":"2010","journal-title":"CNS Neurosci Ther"},{"issue":"8","key":"ref67","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s00702-013-1149-z","article-title":"A further update on the role of excitotoxicity in the pathogenesis of Parkinson&apos;s disease","volume":"121","author":"G Ambrosi","year":"2014","journal-title":"J Neural Transm"},{"issue":"1","key":"ref68","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.expneurol.2009.06.005","article-title":"Impaired glutamate homeostasis and programmed cell death in a chronic MPTP mouse model of Parkinson&apos;s disease","volume":"219","author":"GE Meredith","year":"2009","journal-title":"Exp Neurol"},{"issue":"31","key":"ref69","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.2174\/0929867321666140916120118","article-title":"The glutamate hypothesis in ALS: pathophysiology and drug development","volume":"21","author":"H Blasco","year":"2014","journal-title":"Curr Med Chem"},{"issue":"1","key":"ref70","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ana.410280106","article-title":"Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis","volume":"28","author":"JD Rothstein","year":"1990","journal-title":"Ann Neurol"},{"issue":"1","key":"ref71","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.arcmed.2005.05.014","article-title":"Role of glutamate transporters in the clearance and release of glutamate during ischemia and its relation to neuronal death","volume":"37","author":"A Camacho","year":"2006","journal-title":"Arch Med Res"},{"issue":"3","key":"ref72","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1750-3639.2005.tb00526.x","article-title":"Excitotoxicity in perinatal brain injury","volume":"15","author":"MV Johnston","year":"2005","journal-title":"Brain Pathol"},{"issue":"8","key":"ref73","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/glia.22341","article-title":"Astrocytic regulation of glutamate homeostasis in epilepsy","volume":"60","author":"DA Coulter","year":"2012","journal-title":"Glia"},{"issue":"1","key":"ref74","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.brainresrev.2007.06.026","article-title":"Hyperammonemia-induced toxicity for the developing central nervous system","volume":"56","author":"L Cagnon","year":"2007","journal-title":"Brain Res Rev"},{"issue":"2\u20133","key":"ref75","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0197-0186(00)00026-7","article-title":"Effects of ammonia on glutamate transporter (GLAST) protein and mRNA in cultured rat cortical astrocytes","volume":"37","author":"H Chan","year":"2000","journal-title":"Neurochem Int"},{"issue":"1","key":"ref76","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0168-8278(05)80462-3","article-title":"Extracellular brain glutamate during acute liver failure and during acute hyperammonemia simulating acute liver failure: an experimental study based on in vivo brain dialysis","volume":"20","author":"RJ de Knegt","year":"1994","journal-title":"J Hepatol"},{"issue":"4","key":"ref77","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/hep.510240425","article-title":"Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure","volume":"24","author":"A Michalak","year":"1996","journal-title":"Hepatology"},{"issue":"3","key":"ref78","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/j.1471-4159.1983.tb08057.x","article-title":"The release and neosynthesis of glutamic acid are increased in experimental models of hepatic encephalopathy","volume":"40","author":"F Moroni","year":"1983","journal-title":"J Neurochem"},{"issue":"2","key":"ref79","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0304-3940(91)90408-L","article-title":"Ammonia-induced alterations in glutamate and muscimol binding to cerebellar synaptic membranes","volume":"130","author":"VL Rao","year":"1991","journal-title":"Neurosci Lett"},{"issue":"3","key":"ref80","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/BF02081030","article-title":"Loss of [3H]MK801 binding sites in brain in congenital ornithine transcarbamylase deficiency","volume":"10","author":"L Ratnakumari","year":"1995","journal-title":"Metab Brain Dis"},{"issue":"6","key":"ref81","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1111\/jnc.13200","article-title":"Current approaches to enhance glutamate transporter function and expression","volume":"134","author":"AC Fontana","year":"2015","journal-title":"J Neurochem"},{"issue":"18","key":"ref82","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1007\/s00018-015-1937-8","article-title":"Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease","volume":"72","author":"K Takahashi","year":"2015","journal-title":"Cell Mol Life Sci"},{"issue":"1\u20132","key":"ref83","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neuint.2005.04.006","article-title":"Mechanisms of ammonia-induced cell death in rat cortical neurons: roles of NMDA receptors and glutathione","volume":"47","author":"A Klejman","year":"2005","journal-title":"Neurochem Int"},{"issue":"5398","key":"ref84","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1126\/science.283.5398.70","article-title":"Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain","volume":"283","author":"C Ikonomidou","year":"1999","journal-title":"Science"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"e992","DOI":"10.1038\/cddis.2013.507","article-title":"Human recombinant glutamate oxaloacetate transaminase 1 (GOT1) supplemented with oxaloacetate induces a protective effect after cerebral ischemia","volume":"5","author":"M Perez-Mato","year":"2014","journal-title":"Cell Death Dis"},{"issue":"7811","key":"ref86","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0140-6736(73)90667-3","article-title":"Raised plasma-ornithine and gyrate atrophy of the choroid and retina","volume":"1","author":"O Simell","year":"1973","journal-title":"Lancet"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0203707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T01:44:37Z","timestamp":1751852677000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0203707"}},"subtitle":[],"editor":[{"given":"Jyotshna","family":"Kanungo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,9,10]]},"references-count":86,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0203707","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,10]]}}}