Newly validated biomarkers of brain damage may shed light into the role of oxidative stress in the pathophysiology of neurocognitive impairment in dietary restricted phenylketonuria patients

Rausell, Dolores; García‐Blanco, Ana; Correcher, Patricia; Vitoria, Isidro; Vento, Máximo; Cháfer-Pericás, Consuelo

doi:10.1038/s41390-018-0202-x

Cited by 22 publications

(14 citation statements)

References 72 publications

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“…Tyrosine is an essential amino acid, which is partially synthetized from phenylalanine. The accumulation of phenylpyruvate is toxic to the central nervous system (Rausell et al, 2019). Previous research found that the levels of phenylalanine and tyrosine were remarkably increased in cerebrospinal fluid of patients with regional pain syndrome (Meissner et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

The related mechanism of complete Freund's adjuvant‐induced chronic inflammation pain based on metabolomics analysis

Zhang

Jie

et al. 2021

Biomedical Chromatography

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Chronic inflammation pain is a debilitating disease, and its mechanism still remains poorly understood. This study attempted to illuminate the metabolic mechanism of chronic inflammation pain induced by complete Freund’s adjuvant (CFA) injection, especially at spinal level. The chronic inflammation pain model was established by CFA administration. Behavioral testing including mechanical allodynia and thermal hyperalgesia was performed. Meanwhile, a liquid chromatography–mass spectrometry‐based metabolomics approach was applied to analyze potential metabolic biomarkers. The orthogonal partial least squares discrimination analysis mode was employed for determining metabolic changes, and a western blot was performed to detect the protein expression change. The results showed that 27 metabolites showed obviously abnormal expression and seven metabolic pathways were significantly enriched, comprising aminoacyl‐tRNA biosynthesis, arginine and proline metabolism, histidine metabolism, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism, and phenylalanine metabolism. Meanwhile, the results showed that the expression of arginase I and nitric oxide levels were elevated in the CFA group compared with the control group, while the argininosuccinate synthetase and argininosuccinatelyase proteins were not significantly different between the groups. These findings demonstrate that metabolic changes of the spinal cord may be implicated in neurotransmitter release and pain conductivity following CFA administration.

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Section: Discussionmentioning

confidence: 99%

The related mechanism of complete Freund's adjuvant‐induced chronic inflammation pain based on metabolomics analysis

Zhang

Jie

et al. 2021

Biomedical Chromatography

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“…Recent papers have validated these techniques for targeting oxidative damage byproducts from fatty acid components of the brain (i.e., docosahexaenoic acid, adrenic acid). [36][37][38][39] Whether employing such alternative analytical methodologies may yield improved performance of DBS-determined biomarker levels is an area for future study. Our study has several limitations.…”

Section: Discussionmentioning

confidence: 99%

Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy

Massaro

Bammler

et al. 2019

Pediatr Res

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BACKGROUND: Data correlating dried blood spots (DBS) and plasma concentrations for neonatal biomarkers of brain injury are lacking. We hypothesized that candidate biomarker levels determined from DBS can serve as a reliable surrogate for plasma levels. METHODS: In the context of a phase II multi-center trial evaluating erythropoietin for neuroprotection in neonatal encephalopathy (NE), DBS were collected at enrollment (< 24 h), day 2, 4, and 5. Plasma was collected with the first and last DBS. The relationship between paired DBS-plasma determinations of brain-specific proteins and cytokines was assessed by correlation and Bland-Altman analyses. For analytes with consistent DBS-plasma associations, DBS-derived biomarker levels were related to brain injury by MRI and 1-year outcomes. RESULTS: We enrolled 50 newborns with NE. While S100B protein, tumor necrosis factor α, interleukin (IL)1 β, IL-6, IL-8 demonstrated significant DBS-plasma correlations, Bland-Altman plots demonstrated that the methods are not interchangeable, with a 2 to 4-fold error between measurements. No significant relationships were found between DBS levels of TNFα, IL-6, and IL-8 and outcomes. CONCLUSION: Further work is needed to optimize elution and assay methods before using DBS specimens as a reliable surrogate for plasma levels of candidate brain injury biomarkers in NE.

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“…100 **evidence for this came from a single cross-sectional study 98 and, therefore, observed deficits in cognitive performance may be due to individual differences and do not necessarily reflect the trajectory of cognitive ageing in PKU. 82 increased ROS production 51,83,84 inhibition of antioxidant enzymes 51,85 reduced gray matter volume [86][87][88][89] • Decreased Tyr and Trp r and other LNAA 1 decreased dopamine and norepinephrine (Tyr) and serotonin (Trp) 1 disruptions in protein synthesis 90…”

Section: Gastrointestinal Pathologymentioning

confidence: 99%

Phenylketonuria, co‐morbidity, and ageing: A review

Vardy

MacDonald

Ford³

et al. 2020

J of Inher Metab Disea

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Phenylketonuria (PKU) is a metabolic condition which, left untreated, results in severe and irreversible brain damage. Newborn screening and the development of the low phenylalanine (Phe) diet have transformed the outcomes for people with PKU. Those who have benefited from early treatment are now approaching their fifth and sixth decade. It is therefore timely to consider multi‐morbidity in PKU and the effects of ageing, in parallel with the wider benefits of emerging treatment options in addition to dietary relaxation. We have conducted the first literature review of co‐morbidity and ageing in the context of PKU. Avenues explored have emerged from limited study of multi‐morbidity to date and the knowledge and critical enquiry of the authors. Findings suggest PKU to have a wider impact than brain development, and result in several intriguing questions that require investigation to attain the best outcomes for people with PKU in adulthood moving through to older age. We recognise the difficulty in studying longitudinal outcomes in rare diseases and emphasise the necessity to develop PKU registries and cohorts that facilitate well‐designed studies to answer some of the questions raised in this review. Whilst awaiting new information in these areas we propose that clinicians engage with patients to make personalised and well‐informed decisions around Phe control and assessment for co‐morbidity.

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Newly validated biomarkers of brain damage may shed light into the role of oxidative stress in the pathophysiology of neurocognitive impairment in dietary restricted phenylketonuria patients

Cited by 22 publications

References 72 publications

The related mechanism of complete Freund's adjuvant‐induced chronic inflammation pain based on metabolomics analysis

The related mechanism of complete Freund's adjuvant‐induced chronic inflammation pain based on metabolomics analysis

Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy

Phenylketonuria, co‐morbidity, and ageing: A review

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