6 research outputs found
Aging and microglial response following systemic stimulation with escherichia coli in mice
Systemic infection is an important risk factor for the development cognitive impairment and neurodegeneration in older people. Animal experiments show that systemic challenges with live bacteria cause a neuro-inflammatory response, but the effect of age on this response in these models is unknown. Young (2 months) and middle-aged mice (13-14 months) were intraperitoneally challenged with live Escherichia coli (E. coli) or saline. The mice were sacrificed at 2, 3 and 7 days after inoculation; for all time points, the mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h after inoculation. Microglial response was monitored by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry, and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators. We observed an increased microglial cell number and moderate morphologically activated microglial cells in middle-aged mice, as compared to young mice, after intraperitoneal challenge with live E. coli. Flow cytometry of microglial cells showed higher CD45 and CD11b expressions in middle-aged infected mice compared to young infected mice. The brain expression levels of pro-inflammatory genes were higher in middle-aged than in young infected mice, while middle-aged infected mice had similar expression levels of these genes in the systemic compartment. We conclude that systemic challenge with live bacteria causes an age-dependent neuro-inflammatory and microglial response. Our data show signs of an age-dependent disconnection of the inflammatory transcriptional signature between the brain and the systemic compartment.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care
Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause lifethreatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation
of host and pathogen is known to play a role in invasive pneumococcal disease, though to
what extent is unknown. In a genome-wide association study of human and pathogen we
show that human variation explains almost half of variation in susceptibility to pneumococcal
meningitis and one-third of variation in severity, identifying variants in CCDC33 associated
with susceptibility. Pneumococcal genetic variation explains a large amount of invasive
potential (70%), but has no effect on severity. Serotype alone is insufficient to explain
invasiveness, suggesting other pneumococcal factors are involved in progression to invasive
disease. We identify pneumococcal genes involved
Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation
Variation in coagulation and fibrinolysis genes evaluated for their contribution to cerebrovascular complications in adults with bacterial meningitis in the Netherlands
Genetics of disease, diagnosis and treatmen