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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cerebral Infarction

Intervention / Treatment
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* Other: Usual care patients in neurology department
* Biological: blood and urines sampling
* Procedure: Psychiatric evaluation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients presenting cerebral infarction<br>no intervention of health product administration, | Other: Usual care patients in neurology department<br>* patients characteristics, history, clinical signs chronology and usual medical care by the emergency units, cerebral infarction area<br>Biological: blood and urines sampling<br>* Collection samples for biochemical determinations of serotonin pathway and kynurenine pathway parameters determinations<br>Procedure: Psychiatric evaluation<br>* depression scale, impulsivity scale, hostility scale , tobacco consumption questioning<br>|
| Other: Historical controls<br>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 | Biological: blood and urines sampling<br>* Collection samples for biochemical determinations of serotonin pathway and kynurenine pathway parameters determinations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of serotonin pathway parameters concentrations in blood and urine samples | 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. | Day 1 | 
| Measure of serotonin pathway parameters in blood samples | 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) | Day 1 | 
| Measure of serotonin pathway parameters in blood and urine samples | 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 | Day 2 | 
| Measure of serotonin pathway parameters in blood and urine samples | 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 | Month 3 | 
| Measure of kynurenin pathway parameters in blood samples | 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 . | Day 1 | 
| Measure of kynurenin pathway parameters in blood samples | 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 . | Day 2 | 
| Measure of kynurenin pathway parameters in blood samples | 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 . | Month 3 |