TSK (Tryptophan - Serotonin - Kynurenine) Biomarkers Assessment in Stroke

Simultaneous Assessments of Serotonin and Kynurenine Pathways Parameters in Patients Shortly (Less Than 4 Hours and a Half) After the Onset of a Cerebral Infarction

Single-center, prospective, descriptive and biomedical research with controls, without health product. Depression is the second risk factor for stroke as tobacco smoking following hypertension. Peripheral abnormalities in serotonin parameters were described in depression and tobacco smoking. The investigators hypothesized dysregulations in pathways of serotonin (5-HT), which has notably complex vasomotor effects and of kynurenine which could have cognitive dysfunction effects. The aim of this study is to evaluate simultaneously the involvement of serotonin and kynurenine pathways parameters in patients suffering from a cerebral infarction shortly after the onset (less than 4 hours and a half), within a 2 days follow-up (Day 1 and Day 2) and 3 months after the cerebral infarction.

Tryptophan (TRP), an essential aminoacid, is metabolized in the serotonin (5-HT) or in the kynurenine (KYN) pathway. Serotonin is catabolized to 5-HIAA (5-hydroxyindole amino acid) by monoamine oxidase A (MAOA). The TRP to KYN transformation is regulated by indoleamine 2,3-dioxygenase (IDO). The primary objective was the measurements of serotonin and kynurenine pathways parameters which were performed in blood and urine samples using different HPLC techniques and of serotonin transporters and receptors which were determined in blood platelets. The results in patients were compared to those measured in controls matched for age, gender, tobacco consumption and season of inclusion. The secondary objective was to evaluate the potential relationships between these 5-HT and Kyn pathways biomarkers concentrations, MAOA and IDO enzymatic activations and clinical outcome and criteria.

no intervention of health product administration, patients characteristics, history, matched with patients for age, gender, tobacco consumption and season of inclusion, free of neurologic or psychiatric disease or psychotropic medications or medications known to impact on serotonin

patients characteristics, history, clinical signs chronology and usual medical care by the emergency units, cerebral infarction area

Collection samples for biochemical determinations of serotonin pathway and kynurenine pathway parameters determinations

platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods.

Blood platelets assessements of serotonin (5-HT) transporters using [3H]paroxetine ligand ( fmol/mg proteins) and 5-HT2A receptors using [3H]MDL-100,907 ligand ( fmol/mg proteins)

platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods

platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods

The first and regulatory enzyme of the kynurenine pathway is the indoleamine-2,3-dioxygenase (IDO). Plasma tryptophan (µM) and plasma kynurenine (µM) concentrations [Trp] and [Kyn] were quantified with HPLC method. [Trp] / [Kyn] ratio (in AU, Arbitrary Units) was used as index for IDO activity .

The first and regulatory enzyme of the kynurenine pathway is the indoleamine-2,3-dioxygenase (IDO). Plasma tryptophan (µM) and plasma kynurenine (µM) concentrations [Trp] and [Kyn] were quantified with HPLC method. [Trp] / [Kyn] ratio (in AU, Arbitrary Units) was used as index for IDO activity .

The first and regulatory enzyme of the kynurenine pathway is the indoleamine-2,3-dioxygenase (IDO). Plasma tryptophan (µM) and plasma kynurenine (µM) concentrations [Trp] and [Kyn] were quantified with HPLC method. [Trp] / [Kyn] ratio (in AU, Arbitrary Units) was used as index for IDO activity .

For patients: patient characteristics, history, clinical signs chronology and medical care by pre-hospital then hospital neurology intensive care, MRI diagnosis validation, cerebral infarction area. For controls : patient characteristics, history.

Interview with the patient, or a patient closely related, or a physician. Scale for depression scores (simplified depression scale from Whooley 2006), concerning the 2 weeks before stroke

Interview with the patient, or a patient closely related, or a physician. Scale for impulsivity scores ( Barratt Impulsiveness scale), concerning the 2 weeks before stroke

Study population : patients who had positive MRI diagnosis of cerebral infarction less than 4.30 hours after the clinical onset. Experimental group : Inclusion Criteria: Age ≥ 18 ans Cerebral infarction with a medical care to emergencies less than 4.30 hours after the symptoms onset. Written informed consent signed by the patient, or by a trusted person then by the patient himself if permitted by his condition. Exclusion Criteria: Cerebral infarction with a medical care to emergencies more than 4.30 hours after the symptoms onset. Patient with subarachnoid haemorrhage, cerebral hematoma. Pregnant woman Patient under guardianship or trusteeship, or safeguard justice. Control group : Matching criteria for age, gender, tobacco smoking, inclusion season