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

Lucinéia Gainski Danielski, Amanda Della Giustina, Mariana Pereira Goldim, Drielly Florentino, Khiany Mathias, Leandro Garbossa, Rosiane de Bona Schraiber, Ana Olívia Martins Laurentino, Marina Goulart, Monique Michels, Karina Barbosa de Queiroz, Markus Kohlhof, Gislaine Tezza Rezin, Jucélia Jeremias Fortunato, Joao Quevedo, Tatiana Barichello, Felipe Dal-Pizzol, Roney S. Coimbra, Fabricia Petronilho

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5255-5268
Number of pages14
JournalMolecular Neurobiology
Volume55
Issue number6
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Keywords

  • Brain damage
  • Neuroinflammation
  • Oxidative stress
  • Sepsis
  • Tryptophan
  • Vitamin B

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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