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

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-α, IL-1β, 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 10 μL sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration 1 × 106 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-α and IL-1β analysis. In the hippocampus, the CINC-1 and IL-1β levels were found increased at 6 h, 12 h and 24 h after pneumococcal meningitis induction. In the cortex the levels of the CINC-1 were increased at 6 h, 12 h and 24 h. The IL-1β and TNF-α were increased at 12 h and 24 h. The level of IL-6 was increased only after 24 h after pneumococcal meningitis induction. In cerebrospinal fluid, the TNF-α was increased at 12 h, 24 h and IL-1 was increased at 24 h after S. pneumoniae induction. The blood-brain barrier breakdown in hippocampus and cortex were observed at 12 h until 24 h 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.