vitamin-b-12 and Meningitis--Pneumococcal

The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl.. Eleven-day-old rats were infected with. In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug.. B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.

Topics: Animals; Disease Models, Animal; Histones; Humans; Meningitis, Pneumococcal; Neuroprotective Agents; Rats; Streptococcus pneumoniae; Vitamin B 12

Bacterial meningitis (BM) causes apoptotic damage to the hippocampus and homocysteine (Hcy) accumulation to neurotoxic levels in the cerebrospinal fluid of children. The Hcy pathway controls bioavailability of methyl, and its homeostasis can be modulated by vitamin B. Eleven-day old rats were intracysternally infected with Streptococcus pneumoniae serotype 3, or saline, treated with B. B. Hcy is likely to play a central role in hippocampal damage in the infant rat model of BM, and B

Topics: Animals; Apoptosis; Disease Models, Animal; DNA Methylation; Hippocampus; Meningitis, Pneumococcal; Neuroprotective Agents; Promoter Regions, Genetic; Rats; Rats, Wistar; Streptococcus pneumoniae; Vitamin B 12