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. 2022 Jan 11:12:782317.
doi: 10.3389/fneur.2021.782317. eCollection 2021.

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

Luigi F Saccaro  1 , Fernando Pico  1 , Marie-Laure Chadenat  1 , Olivier Richard  2 , Jean-Marie Launay  3 , Brigitte Bastenaire  4 , Philippe Jullien  5 , Jerôme Lambert  6 , Vincent Feuga  7 , Maryline Macquet  8 , Jacques Callebert  3 , Yves Lambert  2 , Odile Spreux-Varoquaux  8
Affiliations

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

Luigi F Saccaro et al. Front Neurol. .

Abstract

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-HT2A receptor (5-HT2AR) 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-HT2AR 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.

Keywords: 5-HT; acute ischemic stroke (AIS); biomarkers; kynurenine; serotonin; transient ischemic attack (TIA); tryptophan.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Platelet markers at day 0. (A) Blood platelet 5-HT transporter (SERT) density in patients (P) and controls (C) (p = 10−5). (B) Blood platelet 5-HT receptor (5-HT2AR) density in patients (P) and controls (C) (p < 10−6). Each gray square indicates the interquartile range (IQR) and the black line the median.
Figure 2
Figure 2
Urinary markers at day 0. (A) Urinary 5-HT in patients (P) and controls (C) (p = 0.011). (B) Urinary 5-HIAA in patients (P) and controls (C) (p = 0.003). Each gray square indicates the IQR and the black line the median.
See this image and copyright information in PMC

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