Title:Protection of Blood Brain Barrier Integrity and Modulation of Inflammatory Mediators During Treatment of Pneumococcal Meningitis with Daptomycin or Ceftriaxone
Volume: 11
Issue: 3
Author(s): Tatiana Barichello, Joao Carlos Nepomuceno Goncalves, Jaqueline da Silva Generoso, Lutiana Roque Simoes, Michael Hikaru Tashiro, Jessica de Assis Goularte, Francieli Vuolo, David Henrique Rodrigues, Marcia Carvalho Vilela, Fabricia Petronilho, Antonio Lucio Teixeira and Joao Quevedo
Affiliation:
Keywords:
BDNF, ceftriaxone, cytokine, daptomycin, meningitis, streptococcus pneumonia.
Abstract: Pneumococcal meningitis is associated with neurologic sequelae, such as learning and memory impairment.
Most recently, a nonbacteriolytic antibiotic has been investigated to minimise the inflammatory host response and prevent
cognitive damage. In this study, we compared daptomycin (DPTO) or ceftriaxone (CFX) treatment on the inflammatory
parameters and on the blood-brain barrier (BBB) integrity in experimental pneumococcal meningitis. In the first experiment,
the animals received 10 µl of a Streptococcus pneumoniae suspension or artificial cerebrospinal fluid by
intracerebroventricular (i.c.v.) and were treated with CFX or DPTO at 18 h post-infection. The animals were euthanised at 18,
20, 24, 36 and 40 h post-infection. In the hippocampus, brain-derived neurotrophic factor (BDNF), tumour necrosis factor
alpha (TNF-α), interleukin-6 (IL-6) and IL-10 levels were not different between treatment groups; however, IL-4 and
cytokine-induced neutrophil chemoattractant 1 (CINC-1) levels decreased in the CFX group. In the frontal cortex, TNF-α, IL-
4, IL-6, IL-10 and BDNF levels were not different between treatment groups. Only CINC-1 levels decreased at 40 h postinfection
with CFX treatment. In the second experiment, the animals received DPTO or CFX for 7 days and were euthanised
10 days after pneumococcal meningitis induction. TNF-α, IL-6, IL-10, CINC-1 and BDNF levels were not different between
treatment groups in the hippocampus; however, IL-4 levels decreased in CFX group. In the third experiment, the animals
received 10 µl of an S. pneumoniae suspension or artificial CSF by i.c.v. and were treated with a single dose of CFX or
DTPO antibiotic; assessment of the BBB breakdown showed that both antibiotics prevented the BBB disruption. Both
treatments equally protected the BBB integrity, and there were no significant difference in cytokine production.
