title: Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis.
abstract: 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.
  
  
  RESULTS
  Eleven day old Wistar rats were infected with 1x10(6) 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.
authors: Biology Division, Spiez Laboratory, Federal Office for Civil Protection, Austrasse, CH-3700, Spiez, Switzerland. stephen.leib@babs.admin.ch.
authors: Denise C
authors: DC
authors: Zysset-Burri
authors: Caroline L
authors: CL
authors: Bellac
authors: Stephen L
authors: SL
authors: Leib
authors: Matthias
authors: M
authors: Wittwer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D025101:Vitamin B 6 / Q000008:administration & dosage*
chemical_list: D025101:Vitamin B 6
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