Cerebrospinal fluid metabolites in tryptophan-kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation.

Yan, J; Kuzhiumparambil, U; Bandodkar, A; Bandodkar, S; Dale, RC; Fu, S

Cerebrospinal fluid metabolites in tryptophan-kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation.

Yan, J Kuzhiumparambil, U

Bandodkar, A Bandodkar, S Dale, RC Fu, S

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Developmental Medicine and Child Neurology, 2021, 63, (5), pp. 552-559
Issue Date:: 2021-02-01

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Field	Value	Language
dc.contributor.author	Yan, J
dc.contributor.author	Kuzhiumparambil, U https://orcid.org/0000-0003-0582-6779
dc.contributor.author	Bandodkar, A
dc.contributor.author	Bandodkar, S
dc.contributor.author	Dale, RC
dc.contributor.author	Fu, S https://orcid.org/0000-0002-6238-3612
dc.date.accessioned	2022-01-18T22:50:06Z
dc.date.available	2020-11-13
dc.date.available	2022-01-18T22:50:06Z
dc.date.issued	2021-02-01
dc.identifier.citation	Developmental Medicine and Child Neurology, 2021, 63, (5), pp. 552-559
dc.identifier.issn	0012-1622
dc.identifier.issn	1469-8749
dc.identifier.uri	http://hdl.handle.net/10453/153292
dc.description.abstract	Aim To explore the cerebrospinal fluid (CSF) metabolite features in acute neuroinflammatory diseases and identify potential biomarkers to diagnose and monitor neuroinflammation. Method A cohort of 14 patients (five females, nine males; mean [median] age 7y 9mo [9y], range 6mo–13y) with acute encephalitis (acute disseminated encephalomyelitis n=6, unknown suspected viral encephalitis n=3, enteroviral encephalitis n=2, seronegative autoimmune encephalitis n=2, herpes simplex encephalitis n=1) and age-matched non-inflammatory neurological disease controls (n=14) were investigated using an untargeted metabolomics approach. CSF metabolites were analyzed with liquid chromatography coupled to high resolution mass spectrometry, followed by subsequent multivariate and univariate statistical methods. Results A total of 35 metabolites could be discriminated statistically between the groups using supervised orthogonal partial least squares discriminant analysis and analysis of variance. The tryptophan-kynurenine pathway contributed nine key metabolites. There was a statistical increase of kynurenine, quinolinic acid, and anthranilic acid in patients with encephalitis, whereas tryptophan, 3-hydroxyanthrnailic acid, and kynurenic acid were decreased. The nitric oxide pathway contributed four metabolites, with elevated asymmetric dimethylarginine and argininosuccinic acid, and decreased arginine and citrulline in patients with encephalitis. An increase in the CSF kynurenine/tryptophan ratio (p<0.001), anthranilic acid/3-hydroxyanthranilic acid ratio (p<0.001), asymmetric dimethylarginine/arginine ratio (p<0.001), and neopterin (p<0.001) strongly predicted neuroinflammation. Interpretation The combination of alterations in the tryptophan-kynurenine pathway, nitric oxide pathway, and neopterin represent a useful potential panel for neuroinflammation and holds potential for clinical translation practice. What this paper adds The kynurenine/tryptophan and anthranilic acid/3-hydroxyanthranilic acid ratios hold great potential as biomarkers of neuroinflammation. Elevation of the asymmetric dimethylarginine/arginine ratio in acute brain inflammation shows dysregulation of the nitric oxide pathway.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Developmental Medicine and Child Neurology
dc.relation.isbasedon	10.1111/dmcn.14774
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Pediatrics
dc.subject.mesh	Adolescent
dc.subject.mesh	Biomarkers
dc.subject.mesh	Child
dc.subject.mesh	Child, Preschool
dc.subject.mesh	Encephalitis, Viral
dc.subject.mesh	Encephalomyelitis, Acute Disseminated
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Infant
dc.subject.mesh	Kynurenine
dc.subject.mesh	Male
dc.subject.mesh	Nitric Oxide
dc.subject.mesh	Tryptophan
dc.subject.mesh	Humans
dc.subject.mesh	Encephalitis, Viral
dc.subject.mesh	Encephalomyelitis, Acute Disseminated
dc.subject.mesh	Nitric Oxide
dc.subject.mesh	Tryptophan
dc.subject.mesh	Kynurenine
dc.subject.mesh	Adolescent
dc.subject.mesh	Child
dc.subject.mesh	Child, Preschool
dc.subject.mesh	Infant
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Biomarkers
dc.title	Cerebrospinal fluid metabolites in tryptophan-kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation.
dc.type	Journal Article
utslib.citation.volume	63
utslib.location.activity	England
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - C3 - Climate Change Cluster
pubs.organisational-group	/University of Technology Sydney/Strength - CFS - Centre for Forensic Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
utslib.copyright.status	closed_access	*
pubs.consider-herdc	true
dc.date.updated	2022-01-18T22:50:05Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	63
utslib.citation.issue	5

Abstract:

Aim To explore the cerebrospinal fluid (CSF) metabolite features in acute neuroinflammatory diseases and identify potential biomarkers to diagnose and monitor neuroinflammation. Method A cohort of 14 patients (five females, nine males; mean [median] age 7y 9mo [9y], range 6mo–13y) with acute encephalitis (acute disseminated encephalomyelitis n=6, unknown suspected viral encephalitis n=3, enteroviral encephalitis n=2, seronegative autoimmune encephalitis n=2, herpes simplex encephalitis n=1) and age-matched non-inflammatory neurological disease controls (n=14) were investigated using an untargeted metabolomics approach. CSF metabolites were analyzed with liquid chromatography coupled to high resolution mass spectrometry, followed by subsequent multivariate and univariate statistical methods. Results A total of 35 metabolites could be discriminated statistically between the groups using supervised orthogonal partial least squares discriminant analysis and analysis of variance. The tryptophan-kynurenine pathway contributed nine key metabolites. There was a statistical increase of kynurenine, quinolinic acid, and anthranilic acid in patients with encephalitis, whereas tryptophan, 3-hydroxyanthrnailic acid, and kynurenic acid were decreased. The nitric oxide pathway contributed four metabolites, with elevated asymmetric dimethylarginine and argininosuccinic acid, and decreased arginine and citrulline in patients with encephalitis. An increase in the CSF kynurenine/tryptophan ratio (p<0.001), anthranilic acid/3-hydroxyanthranilic acid ratio (p<0.001), asymmetric dimethylarginine/arginine ratio (p<0.001), and neopterin (p<0.001) strongly predicted neuroinflammation. Interpretation The combination of alterations in the tryptophan-kynurenine pathway, nitric oxide pathway, and neopterin represent a useful potential panel for neuroinflammation and holds potential for clinical translation practice. What this paper adds The kynurenine/tryptophan and anthranilic acid/3-hydroxyanthranilic acid ratios hold great potential as biomarkers of neuroinflammation. Elevation of the asymmetric dimethylarginine/arginine ratio in acute brain inflammation shows dysregulation of the nitric oxide pathway.

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