The role of tryptophan catabolism along the kynurenine pathway in acute ischemic stroke.
Post-stroke inflammation may induce upregulation of the kynurenine (KYN) pathway for tryptophan (TRP) oxidation, resulting in neuroprotective (kynurenic acid, KA) and neurotoxic metabolites (3-hydroxyanthranillic acid, 3-HAA). We investigated whether activity of the kynurenine pathway in acute ischemic stroke is related to initial stroke severity, long-term stroke outcome and the ischemia-induced inflammatory response. Plasma concentrations of TRP and its metabolites were measured in 149 stroke patients at admission, at 24 h, at 72 h and at day 7 after stroke onset. We evaluated the relation between the KYN/TRP ratio, the KA/3-HAA ratio and stroke severity, outcome and inflammatory parameters (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and neutrophil/lymphocyte ratio (NLR)). KYN/TRP but not KA/3-HAA correlated with the NIHSS score and with the infarct volume. Patients with poor outcome had higher mean KYN/TRP ratios than patients with more favourable outcome. The KYN/TRP ratio at admission correlated with CRP levels, ESR and NLR. The activity of the kynurenine pathway for tryptophan degradation in acute ischemic stroke correlates with stroke severity and long-term stroke outcome. Tryptophan oxidation is related to the stroke-induced inflammatory response.
Brouns
Raf
R
Department of Neurology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium.
Verkerk
Robert
R
Aerts
Tony
T
De Surgeloose
Didier
D
Wauters
Annick
A
Scharpé
Simon
S
De Deyn
Peter P
PP
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014364:Tryptophan / Q000378:metabolism*
D016166:Free Radical Scavengers; D015095:3-Hydroxyanthranilic Acid; D007737:Kynurenine; D014364:Tryptophan