The role of tryptophan catabolism along the kynurenine pathway in acute ischemic stroke

Neurochem Res. 2010 Sep;35(9):1315-22. doi: 10.1007/s11064-010-0187-2. Epub 2010 May 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyanthranilic Acid / metabolism
  • Aged
  • Aged, 80 and over
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Free Radical Scavengers / metabolism
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Kynurenine / metabolism*
  • Male
  • Stroke / metabolism*
  • Stroke / pathology
  • Stroke / physiopathology
  • Tryptophan / metabolism*

Substances

  • Free Radical Scavengers
  • 3-Hydroxyanthranilic Acid
  • Kynurenine
  • Tryptophan