Pneumococcal meningitis causes accumulation of neurotoxic kynurenine metabolites in brain regions prone to injury

Bellac, Caroline L.; Coimbra, Roney S.; Christen, Stephan; Leib, Stephen L. (2006). Pneumococcal meningitis causes accumulation of neurotoxic kynurenine metabolites in brain regions prone to injury. Neurobiology of disease, 24(2), pp. 395-402. Amsterdam: Elsevier 10.1016/j.nbd.2006.07.014

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Pneumococcal meningitis (PM) is characterized by an intense inflammatory host reaction that contributes to the development of cortical necrosis and hippocampal apoptosis. Inflammatory conditions in the brain are known to induce tryptophan degradation along the kynurenine pathway, resulting in accumulation of neurotoxic metabolites. In the present study, we investigated the contribution of the kynurenine pathway to brain injury in experimental PM by measuring the concentration of its metabolites and the enzymatic activities and mRNA levels of its major enzymes in the vulnerable brain regions. In the late phase of acute PM, we found a significant transcriptional upregulation of kynurenine-3-hydroxylase and an accumulation of the neurotoxic metabolites 3-hydroxykynurenine (3-HKYN) and 3-hydroxyanthranilic acid in cortex and hippocampus. The positive correlation between the concentration of 3-HKYN and the extent of hippocampal apoptosis adds support to the concept that 3-HKYN contributes to brain injury in PM.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
UniBE Contributor:	Christen, Stephan, Leib, Stephen
ISSN:	0969-9961
ISBN:	16956766
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:46
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1016/j.nbd.2006.07.014
PubMed ID:	16956766
Web of Science ID:	000241594900019
URI:	https://boris.unibe.ch/id/eprint/19170 (FactScience: 1586)