Tesi etd-11122020-130722
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Tipo di tesi
Corso Ordinario Ciclo Unico 6 Anni
Autore
SACCARO, LUIGI FRANCESCO
URN
etd-11122020-130722
Titolo
Platelet, plasma and urinary tryptophan-serotonin-kynurenine axis markers in hyperacute brain ischemia: a prospective, case-control study
Struttura
Cl. Sc. Sperimentali - Medicina
Corso di studi
SCIENZE MEDICHE - SCIENZE MEDICHE
Commissione
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
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
Parole chiave
- acido omovanillico
- attacco ischemico transitorio
- biomarker plasmatico
- biomarker urinario
- caso-controllo
- cerebrovascular diseases
- chinurenina
- clinical study
- homovanillic acid
- ictus ischemico
- ischemia
- malattie cerebrovascolari
- NIHSS
- piastrine
- Rankin
- serotonina
- studio clinico
- triptofano
Data inizio appello
15/12/2020;
Disponibilità
parziale
Riassunto analitico
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 (<4.5h) of brain ischemia platelet, plasmatic and urinary tryptophan-serotonin-kynurenine axis markers, in transient ischemic attack (TIA) and acute ischemic stroke (AIS).
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.
Results. At D0, as compared to controls, patients exhibited a lower (P=0.00001) platelet SERT density, an elevated (P<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.
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.
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.
Results. At D0, as compared to controls, patients exhibited a lower (P=0.00001) platelet SERT density, an elevated (P<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.
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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