The cerebral protective effect and mechanism of action of vitamin B6 adjuvant ceftriaxone in experimental pneumococcal meningitis.
Brain Res. 2018 Sep 15 ;1695:53-64. Epub 2018 May 22. PMID: 29800553
BACKGROUND: Pneumococcal meningitis is one of the most common infectious diseases with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 (vitB6) is an important vitamin which acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan through the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status. The aim of this study was to investigate the neuroprotective effect of adjuvant treatment with vitB6 in pneumococcal meningitis.
METHODS: The effects of vitB6 on the clinical symptoms, the expression of kynureninase (KYN), Kynurenic acid (KYNA), nicotinamide adenine dinucleotide (NAD) and cytokines in brain tissue and memory of infant Wistar rats subjected to pneumococcal meningitis were researched. At the same time, Kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 was applied in order to further investigate the brain protective effect of vitB6 in bacterial meningitis.
RESULTS: Adjuvant therapy of bacterial meningitis with vitB6 could improve the clinical symptoms, learning performance, lead to the maintenance of cellular NAD+ and ATP homeostasis and significantly down-regulate the levels of cytokines in the brain tissue by affecting the KYN pathway.
CONCLUSIONS: Adjuvant treatment with vitB6 in pneumococcal meningitis could exert neuroprotective effect via increasing the preservation of cellular energy through affecting the KYN pathway and reducing of the inflammatory response.