Protection of Blood Brain Barrier Integrity and Modulation of Inflammatory Mediators During Treatment of Pneumococcal Meningitis with Daptomycin or Ceftriaxone

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.

Cite this article as:

Barichello Tatiana, Goncalves Carlos Nepomuceno Joao, Generoso da Silva Jaqueline, Simoes Roque Lutiana, Tashiro Hikaru Michael, Goularte de Assis Jessica, Vuolo Francieli, Rodrigues Henrique David, Vilela Carvalho Marcia, Petronilho Fabricia, Teixeira Lucio Antonio and Quevedo Joao, Protection of Blood Brain Barrier Integrity and Modulation of Inflammatory Mediators During Treatment of Pneumococcal Meningitis with Daptomycin or Ceftriaxone, Current Neurovascular Research 2014; 11 (3) . https://dx.doi.org/10.2174/1567202611666140520123424