The Role of Tryptophan Catabolism along the Kynurenine Pathway in Acute Ischemic Stroke |
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Authors: | Raf Brouns Robert Verkerk Tony Aerts Didier De Surgeloose Annick Wauters Simon Scharpé Peter P. De Deyn |
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Affiliation: | (1) Department of Neurology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium;(2) Laboratory for Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium;(3) Department of Neurology and Memory Clinic, ZNA Middelheim Hospital, Antwerp, Belgium;(4) Laboratory for Medical Biochemistry, University of Antwerp, Antwerp, Belgium;(5) Department of Radiology, ZNA Middelheim Hospital, Antwerp, Belgium;(6) Department of Clinical Biology, ZNA Middelheim Hospital, Antwerp, Belgium; |
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Abstract: | 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. |
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