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Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study

Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyper...

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Autores principales: Saccaro, Luigi F., Pico, Fernando, Chadenat, Marie-Laure, Richard, Olivier, Launay, Jean-Marie, Bastenaire, Brigitte, Jullien, Philippe, Lambert, Jerôme, Feuga, Vincent, Macquet, Maryline, Callebert, Jacques, Lambert, Yves, Spreux-Varoquaux, Odile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787359/
https://www.ncbi.nlm.nih.gov/pubmed/35087467
http://dx.doi.org/10.3389/fneur.2021.782317
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author Saccaro, Luigi F.
Pico, Fernando
Chadenat, Marie-Laure
Richard, Olivier
Launay, Jean-Marie
Bastenaire, Brigitte
Jullien, Philippe
Lambert, Jerôme
Feuga, Vincent
Macquet, Maryline
Callebert, Jacques
Lambert, Yves
Spreux-Varoquaux, Odile
author_facet Saccaro, Luigi F.
Pico, Fernando
Chadenat, Marie-Laure
Richard, Olivier
Launay, Jean-Marie
Bastenaire, Brigitte
Jullien, Philippe
Lambert, Jerôme
Feuga, Vincent
Macquet, Maryline
Callebert, Jacques
Lambert, Yves
Spreux-Varoquaux, Odile
author_sort Saccaro, Luigi F.
collection PubMed
description Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (<4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients. Methods: This study included 28 patients (24 AIS and 4 TIA) and 29 controls. The blood and urine samples of patient were collected within 4.5 h of symptoms onset (day 0, D0), then at 24 h and 3 months. Control blood and urine samples were collected once (D0). The TSK axis markers measured were platelet serotonin transporter (SERT) and 5-HT(2A) receptor (5-HT(2A)R) densities and platelet, plasma, and urinary 5-HT, plasma and urinary 5-hydroxyindole acetic acid (5-HIAA), and plasma kynurenine and tryptophan (TRP) levels. Results: At D0, patients exhibited a lower (p = 10(−5)) platelet SERT density, higher (p < 10(−6)) platelet 5-HT(2A)R density, higher (p = 10(−5)) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (p = 0.011) and 5-HIAA (p = 0.003) levels than controls. Conclusions: We observed, for the first time, a hyperacute dysregulation of the serotonergic axis, and hyperacute and long-lasting activation of the tryptophan-kynurenine pathway in brain ischemia.
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spelling pubmed-87873592022-01-26 Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study Saccaro, Luigi F. Pico, Fernando Chadenat, Marie-Laure Richard, Olivier Launay, Jean-Marie Bastenaire, Brigitte Jullien, Philippe Lambert, Jerôme Feuga, Vincent Macquet, Maryline Callebert, Jacques Lambert, Yves Spreux-Varoquaux, Odile Front Neurol Neurology Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (<4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients. Methods: This study included 28 patients (24 AIS and 4 TIA) and 29 controls. The blood and urine samples of patient were collected within 4.5 h of symptoms onset (day 0, D0), then at 24 h and 3 months. Control blood and urine samples were collected once (D0). The TSK axis markers measured were platelet serotonin transporter (SERT) and 5-HT(2A) receptor (5-HT(2A)R) densities and platelet, plasma, and urinary 5-HT, plasma and urinary 5-hydroxyindole acetic acid (5-HIAA), and plasma kynurenine and tryptophan (TRP) levels. Results: At D0, patients exhibited a lower (p = 10(−5)) platelet SERT density, higher (p < 10(−6)) platelet 5-HT(2A)R density, higher (p = 10(−5)) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (p = 0.011) and 5-HIAA (p = 0.003) levels than controls. Conclusions: We observed, for the first time, a hyperacute dysregulation of the serotonergic axis, and hyperacute and long-lasting activation of the tryptophan-kynurenine pathway in brain ischemia. Frontiers Media S.A. 2022-01-11 /pmc/articles/PMC8787359/ /pubmed/35087467 http://dx.doi.org/10.3389/fneur.2021.782317 Text en Copyright © 2022 Saccaro, Pico, Chadenat, Richard, Launay, Bastenaire, Jullien, Lambert, Feuga, Macquet, Callebert, Lambert and Spreux-Varoquaux. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Saccaro, Luigi F.
Pico, Fernando
Chadenat, Marie-Laure
Richard, Olivier
Launay, Jean-Marie
Bastenaire, Brigitte
Jullien, Philippe
Lambert, Jerôme
Feuga, Vincent
Macquet, Maryline
Callebert, Jacques
Lambert, Yves
Spreux-Varoquaux, Odile
Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study
title Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study
title_full Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study
title_fullStr Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study
title_full_unstemmed Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study
title_short Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study
title_sort platelet, plasma, urinary tryptophan-serotonin-kynurenine axis markers in hyperacute brain ischemia patients: a prospective study
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787359/
https://www.ncbi.nlm.nih.gov/pubmed/35087467
http://dx.doi.org/10.3389/fneur.2021.782317
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