No abstract

Background Streptococcus pneumoniae meningitis is a serious inflammatory disease of the central nervous system (CNS) and is associated with high morbidity and mortality rates. The inflammatory processes initiated by recognition of bacterial components contribute to apoptosis in the hippocampal dentate gyrus. Brain-derived neurotrophic factor (BDNF) has long been recommended for the treatment of CNS diseases due to its powerful neuro-survival properties, as well as its recently reported anti-inflammatory and anti-apoptotic effects in vitro and in vivo.MethodsIn this study, we investigated the effects of BDNF-related signaling on the inflammatory response and hippocampal apoptosis in experimental models of pneumococcal meningitis. Pretreatment with exogenous BDNF or the tropomyosin-receptor kinase B (TrkB) inhibitor k252a was performed to assess the activation or inhibition of the BDNF/TrkB-signaling axis prior to intracisternal infection with live S. pneumoniae. At 24 h post-infection, rats were assessed for clinical severity and sacrificed to harvest the brains. Paraffin-embedded brain sections underwent hematoxylin and eosin staining to evaluate pathological severity, and cytokine and chemokine levels in the hippocampus and cortex were evaluated by enzyme-linked immunosorbent assay. Additionally, apoptotic neurons were detected in the hippocampal dentate gyrus by terminal deoxynucleotidyl transferase dUTP-nick-end labeling, key molecules associated with the related signaling pathway were analyzed by real-time polymerase chain reaction and western blot, and the DNA-binding activity of nuclear factor kappa B (NF-κB) was measured by electrophoretic mobility shift assay.ResultsRats administered BDNF exhibited reduced clinical impairment, pathological severity, and hippocampal apoptosis. Furthermore, BDNF pretreatment suppressed the expression of inflammatory factors, including tumor necrosis factor α, interleukin (IL)-1β, and IL-6, and increased the expression of the anti-inflammatory factor IL-10. Moreover, BDNF pretreatment increased TrkB expression, activated downstream phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, and inhibited the myeloid differentiation primary response gene 88 (MyD88)/NF-κB-signaling pathway.ConclusionsThese data suggested that BDNF administration exerted anti-inflammatory and anti-apoptotic effects on an experimental pneumococcal meningitis model via modulation of MyD88/NF-κB- and PI3K/AKT-signaling pathways. Our results indicated that treatment with exogenous BDNF might constitute a potential therapeutic strategy for the treatment of bacterial meningitis.

No abstract

No abstract

During this study a methodology was developed to project growth trends of the motor vehicle population and associated oil demand and carbon dioxide (CO2) emissions in China through 2050. In particular, the numbers of highway vehicles, motorcycles, and rural vehicles were projected under three scenarios of vehicle growth by following different patterns of motor vehicle growth in Europe and Asia. Projections showed that by 2030 China could have more highway vehicles than the United States has today. Three scenarios of vehicle fuel economy were also developed on the basis of current and future policy efforts to reduce vehicle fuel consumption in China and in developed countries. With the vehicle population projections and potential vehicle fuel economy data, it was projected that in 2050 China's on-road vehicles could consume approximately 614 million to 1,016 million metric tons of oil (or 12.4 million to 20.6 million barrels per day) and emit 1.9 billion to 3.2 billion metric tons (or 2.1 billion to 3.5 billion tons) of CO2 each year. Although these projections by no means imply what will happen in the Chinese transportation sector by 2050, they do demonstrate that an uncontained growth in motor vehicles and only incremental efforts to improve fuel economy will certainly result in severe consequences for oil use and CO2 emissions in China.