Vitamin B6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation

Mol Neurobiol. 2018 Jun;55(6):5255-5268. doi: 10.1007/s12035-017-0706-0. Epub 2017 Sep 6.


Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250-300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B6, CLP + saline, and CLP + vit B6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B6 exerts neuroprotective effects in acute and late consequences after sepsis.

Keywords: Brain damage; Neuroinflammation; Oxidative stress; Sepsis; Tryptophan; Vitamin B6.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / pathology
  • Cytokines / metabolism
  • Energy Metabolism / drug effects
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Kaplan-Meier Estimate
  • Kynurenine / metabolism*
  • Lipid Peroxidation / drug effects
  • Male
  • Nitrates / metabolism
  • Nitrites / metabolism
  • Oxidative Stress / drug effects
  • Permeability
  • Peroxidase / metabolism
  • Protein Carbonylation / drug effects
  • Rats, Wistar
  • Sepsis / drug therapy*
  • Sepsis / microbiology*
  • Tryptophan / metabolism
  • Vitamin B 6 / pharmacology
  • Vitamin B 6 / therapeutic use*


  • Cytokines
  • Inflammation Mediators
  • Nitrates
  • Nitrites
  • Kynurenine
  • Vitamin B 6
  • Tryptophan
  • Peroxidase