A kinetic study of the cytokine/chemokines levels and disruption of blood-brain barrier in infant rats after pneumococcal meningitis.

摘要

Bacterial meningitis is an inflammation of the meninges and subarachnoid space that occurs in response of bacteria. Young children are particularly vulnerable to bacterial meningitis, two thirds of meningitis deaths in low-income countries occur among children under the age of fifteen. The main bacterial pathogens causing meningitis beyond the neonatal period are Streptococcus pneumoniae, Haemophilus influenza type b and Neisseria meningitidis. Therefore, the aim of this study is to evaluate the kinetic and the levels of TNF-alpha, IL-1beta, IL-6, IL-10 and CINC-1 in different brain regions as well as the blood-brain barrier permeability after meningitis induced by S. pneumoniae in infant Wistar rats. The animals underwent a magna cistern tap receiving either 10muL sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration 1x10(6)CFU/mL. The animals were killed at different times after induction. The brain was removed and the hippocampus and the cortex were isolated and used for the determination of cytokine/chemokine levels and blood-brain barrier permeability. The cerebrospinal fluid was obtained by puncture of the cisterna magna to TNF-alpha and IL-1beta analysis. In the hippocampus, the CINC-1 and IL-1beta levels were found increased at 6h, 12h and 24h after pneumococcal meningitis induction. In the cortex the levels of the CINC-1 were increased at 6h, 12h and 24h. The IL-1beta and TNF-alpha were increased at 12h and 24h. The level of IL-6 was increased only after 24h after pneumococcal meningitis induction. In cerebrospinal fluid, the TNF-alpha was increased at 12h, 24h and IL-1 was increased at 24h after S. pneumoniae induction. The blood-brain barrier breakdown in hippocampus and cortex were observed at 12h until 24h during meningitis. In conclusion, a peak of pro-inflammatory cytokine/chemokine is associated with disruption of the blood-brain barrier in infants with pneumococcal meningitis.