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Tesi etd-11122020-130722

Type of thesis
Corsi integrativi
Author
SACCARO, LUIGI FRANCESCO
URN
etd-11122020-130722
Title
Platelet, plasma and urinary tryptophan-serotonin-kynurenine axis markers in hyperacute brain ischemia: a prospective, case-control study
Structure
Cl. Sc. Sperimentali - Medicina
Course
SCIENZE MEDICHE - SCIENZE MEDICHE
Committee
Tutor Prof.ssa ANGELONI, DEBORA
Presidente Prof. EMDIN, MICHELE
Relatore Prof. PICO, FERNANDO
Membro COCEANI, FLAVIO
Membro LIONETTI, VINCENZO
Membro RECCHIA, FABIO ANASTASIO
Membro PASSINO, CLAUDIO
Membro MEOLA, MARIO
Membro GIANNONI, ALBERTO
Membro PE', MARIO ENRICO
Membro PETRUCCI, ILARIA
Membro CASIERI, VALENTINA
Keywords
  • piastrine
  • biomarker plasmatico
  • biomarker urinario
  • serotonina
  • triptofano
  • chinurenina
  • ischemia
  • ictus ischemico
  • attacco ischemico transitorio
  • caso-controllo
  • studio clinico
  • clinical study
  • cerebrovascular diseases
  • malattie cerebrovascolari
  • Rankin
  • NIHSS
  • homovanillic acid
  • acido omovanillico
Exam session start date
;
Availability
parziale
Abstract
Background and Purpose. Although ischemic stroke is one of the first causes of morbidity and mortality and has numerous clinical mimics, reliable biomarkers, pathophysiological understanding, and neuroprotective drugs are still lacking. The tryptophan-serotonin-kynurenine axis has been involved in the pathophysiology of brain ischemia, both as a possible risk factor and as a target of brain ischemia-dependent alterations. Previous studies have highlighted alterations in plasmatic markers of the tryptophan-serotonin-kynurenine axis within 24h from the onset of symptoms of brain ischemia. This study aims at evaluating in the hyperacute phase (&lt;4.5h) of brain ischemia platelet, plasmatic and urinary tryptophan-serotonin-kynurenine axis markers, in transient ischemic attack (TIA) and acute ischemic stroke (AIS). <br><br>Methods. 28 patients (23 AIS, 5 TIA) and 29 controls were included in this study. Patients’ blood and urine samples were collected within 4.5h from symptoms (day0, D0) then at 24h and 3 months. Controls’ blood and urine samples were collected once (D0). The tryptophan-serotonin-kynurenine axis markers measured were: platelet serotonin transporter (SERT) and 5-HT2A receptor (5-HT2AR) densities; platelet, plasma and urinary 5-HT; plasma and urinary 5-hydroxyindole acetic acid (5-HIAA); plasma kynurenine and tryptophan.<br><br>Results. At D0, as compared to controls, patients exhibited a lower (P=0.00001) platelet SERT density, an elevated (P&lt;0.000001) platelet 5-HT2AR density, an increased (P=0.00001) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (P=0.011) and 5-HIAA (P=0.003) levels. This is the first study measuring platelet, plasmatic and urinary markers of the tryptophan-serotonin-kynurenine axis within 4.5h from symptoms of brain ischemia.<br><br>Conclusions. In this prospective study of patients in the hyperacute phase of brain ischemia, we observed for the first time a biological pattern of serotonergic axis dysregulation in urinary, plasmatic and platelet markers.
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