Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis

BMC Infectious Diseases

Matthias Wittwer³  Stephen L Leib¹  Caroline L Bellac¹  Denise C Zysset-Burri² 

[1] Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, CH-3010, Bern, Switzerland;Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland;Biology Division, Spiez Laboratory, Federal Office for Civil Protection, Austrasse, CH-3700, Spiez, Switzerland

关键词: Vitamin B6;    Kynurenine pathway;    Streptococcus pneumoniae;    Bacterial meningitis;   

Others  :  1145934
DOI  :  10.1186/1471-2334-13-393

 received in 2013-01-23, accepted in 2013-08-21,  发布年份 2013

【 摘 要 】

Background

Bacterial meningitis caused by Streptococcus pneumoniae leads to death in up to 30% of patients and leaves up to half of the survivors with neurological sequelae. The inflammatory host reaction initiates the induction of the kynurenine pathway and contributes to hippocampal apoptosis, a form of brain damage that is associated with learning and memory deficits in experimental paradigms. Vitamin B6 is an enzymatic cofactor in the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status.

The aim of this study in a pneumococcal meningitis model was to investigate the effect of vitamin B6 on hippocampal apoptosis by histomorphology, by transcriptomics and by measurement of cellular nicotine amide adenine dinucleotide content.

Methods and results

Eleven day old Wistar rats were infected with 1x10⁶ cfu/ml of S. pneumoniae and randomized for treatment with vitamin B6 or saline as controls. Vitamin B6 led to a significant (p > 0.02) reduction of hippocampal apoptosis. According to functional annotation based clustering, vitamin B6 led to down-regulation of genes involved in processes of inflammatory response, while genes encoding for processes related to circadian rhythm, neuronal signaling and apoptotic cell death were mostly up-regulated.

Conclusions

Our results provide evidence that attenuation of apoptosis by vitamin B6 is multi-factorial including down-modulation of inflammation, up-regulation of the neuroprotective brain-derived neurotrophic factor and prevention of the exhaustion of cellular energy stores. The neuroprotective effect identifies vitamin B6 as a potential target for the development of strategies to attenuate brain injury in bacterial meningitis.

【 授权许可】

   
2013 Zysset-Burri et al.; licensee BioMed Central Ltd.

【 图 表 】

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