Journal article

Activation of the kynurenine pathway and increased production of the excitotoxin quinolinic acid following traumatic brain injury in humans

Edwin B Yan, Tony Frugier, Chai K Lim, Benjamin Heng, Gayathri Sundaram, May Tan, Jeffrey V Rosenfeld, David W Walker, Gilles J Guillemin, Maria Cristina Morganti-Kossmann



UNLABELLED: During inflammation, the kynurenine pathway (KP) metabolises the essential amino acid tryptophan (TRP) potentially contributing to excitotoxicity via the release of quinolinic acid (QUIN) and 3-hydroxykynurenine (3HK). Despite the importance of excitotoxicity in the development of secondary brain damage, investigations on the KP in TBI are scarce. In this study, we comprehensively characterised changes in KP activation by measuring numerous metabolites in cerebrospinal fluid (CSF) from TBI patients and assessing the expression of key KP enzymes in brain tissue from TBI victims. Acute QUIN levels were further correlated with outcome scores to explore its prognostic value in TBI re..

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University of Melbourne Researchers


Awarded by Victorian Neurotrauma Initiative/Traffic Accident Commission

Awarded by National Health Medical Research Council

Funding Acknowledgements

This study was funded by the Victorian Neurotrauma Initiative/Traffic Accident Commission project grant D009 and Research Fellowships to EBY and MCM.-K and National Health Medical Research Council Project Grant #436815. GJG is funded by the Australian Research Council (Future Fellowship). Post-mortem brain tissues were received from the Victorian Brain Bank Network, supported by The Florey Institute of Neuroscience and Mental Health, The Alfred and the Victorian Forensic Institute of Medicine and funded by Australia's National Health & Medical Research Council and Parkinson's Victoria.