Protection of blood brain barrier integrity and modulation of inflammatory mediators during treatment of pneumococcal meningitis with daptomycin or ceftriaxone.
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.
Tatiana
T
Barichello
Joao Carlos Nepomuceno
JC
Goncalves
Jaqueline da Silva
Jda S
Generoso
Lutiana Roque
LR
Simoes
Michael Hikaru
MH
Tashiro
Jessica de Assis
Jde A
Goularte
Francieli
F
Vuolo
David Henrique
DH
Rodrigues
Marcia Carvalho
MC
Vilela
Fabricia
F
Petronilho
Antonio Lucio
AL
Teixeira
Laboratorio de Microbiologia Experimental, PPGCS, UNASAU, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. tba@unesc.net.
Joao
J
Quevedo
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002443:Ceftriaxone / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism*; D017576:Daptomycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013997:Time Factors
D000900:Anti-Bacterial Agents; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D002443:Ceftriaxone; D017576:Daptomycin