Inflammation-Induced Catabolism of Tryptophan and Tyrosine in Acute Ischemic Stroke
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Whether the inflammatory response that accompanies acute ischemic stroke induces the kynurenine pathway is currently a matter of conjecture. Activation of this pathway may disturb active metabolites. The aim of this study was thus to characterize the catabolism of tryptophan and tyrosine in acute ischemic stroke (AIS) patients, and its association with cytokines, C-reactive protein, and glucose. Serum levels of 5-hydroxytryptamine, tryptophan catabolites, and competing amino acids and significant ratios of these were measured in 45 AIS patients and compared to those of 40 control subjects. Furthermore, associations between the serum levels of these biomarkers and serum levels of cytokines, C-reactive protein, and glucose were determined. Significantly lower levels of tryptophan and tyrosine in the stroke group indicate increased tryptophan and tyrosine oxidation in acute ischemic stroke, while significantly lowered tryptophan index and tyrosine index indicate a reduced capacity for the synthesis of 5-hydroxytryptamine and catecholamines in the brain, respectively. Furthermore, our findings indicate that the proinflammatory response in acute ischemic stroke may be responsible for a reduced capacity for the biosynthesis of brain catecholamines and mediate neurotoxic effects. Meanwhile, the anti-inflammatory IL-10 may exert a neuroprotective effect and prevent the putative reduced capacity for 5-hydroxytryptamine synthesis in the brain. These mechanisms may be involved in several sequelae following stroke, such as cognitive impairment, depression, and fatigue.
KeywordsAcute ischemic stroke Proinflammatory cytokines Anti-inflammatory cytokines Kynurenine pathway Tryptophan catabolism Tyrosine catabolism
The authors are indebted to the various staff members of Vestre Viken Hospital Trust, Buskerud, Drammen, and Oslo University Hospital, Ullevål, Oslo, for important contributions to the study. The presented work stems from the research project “Poststroke Fatigue,” for which Dr. Hesook Suzie Kim is the project director and Drs. Grethe Eilertsen, Anners Lerdal, and Heidi Ormstad are the principal researchers. The project is funded by the Research Council of Norway for the period from 2007 to 2010 (project no. 176503/V10), and Vestre Viken Hospital Trust..
The study was approved by The Regional Committee For Medical Research Ethics in Norway and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Informed consent was obtained from all patients prior to their inclusion in the study.
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