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 

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

JOURNAL=Frontiers in Neurology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.782317

DOI=10.3389/fneur.2021.782317

ISSN=1664-2295

ABSTRACT=<p><bold>Background and Purpose:</bold> 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 (&lt;4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients.</p><p><bold>Methods:</bold> 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<sub>2A</sub> receptor (5-HT<sub>2A</sub>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.</p><p><bold>Results:</bold> At D0, patients exhibited a lower (<italic>p</italic> = 10<sup>−5</sup>) platelet SERT density, higher (<italic>p</italic> &lt; 10<sup>−6</sup>) platelet 5-HT<sub>2A</sub>R density, higher (<italic>p</italic> = 10<sup>−5</sup>) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (<italic>p</italic> = 0.011) and 5-HIAA (<italic>p</italic> = 0.003) levels than controls.</p><p><bold>Conclusions:</bold> 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.</p>