Aims: Streptococcus pneumoniae infection in acute bacterial meningitis can lead to widespread brain damage and mortality. Inflammatory responses by immune cells in the brain are thought to determine the degree of brain injury. Yet, the mechanisms underlying host responses to pneumococcal meningitis are largely unknown. To explore host responses as a potential therapeutic target for preventing brain injury after pneumococcal meningitis.
Methods: We evaluated signaling mechanisms that minimize neuronal damage caused by pneumococcal infection; specifically, we assessed pathways related to neuronal survival after enhancing estrogen receptor-β (ER-β) expression using a natural therapeutic substance known as ginsenoside Rb1 and Rg3 enhanced ginseng.
Results: Tissue damage caused by bacterial infection was reduced in Rb1/Rg3-treated mice as a result of microglial activation and the inhibition of apoptosis. Furthermore, Rb1 upregulated the expression of brain-derived neurotrophic factor (BDNF) as well as anti-apoptotic factors including Bcl-2 and Bcl-xL. Using BV2 microglial cells in vitro, Rb1 treatment inhibited microglial apoptosis in a manner associated with JAK2/STAT5 phosphorylation.
Conclusion: After S. pneumoniae infection in mice, particularly in female mice, Rb1-containing ginseng increased bacterial clearance and survival. These findings inform our understanding of the host immune response to pneumococcal meningitis.
Keywords: apoptosis; bacterial meningitis; estrogen receptor-β; ginsenoside Rb1, Rg3; microglia; neuroinflammation.
© 2018 John Wiley & Sons Ltd.