Protection of blood brain barrier integrity and modulation of inflammatory mediators during treatment of pneumococcal meningitis with daptomycin or ceftriaxone
| Autor: | Márcia Carvalho Vilela, Fabricia Petronilho, Jaqueline S. Generoso, Lutiana R. Simões, Tatiana Barichello, Francieli Vuolo, João Quevedo, Joao Carlos Nepomuceno Goncalves, Antônio Lúcio Teixeira, Michael Hikaru Tashiro, Jessica A. Goularte, David Henrique Rodrigues |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Time Factors medicine.drug_class medicine.medical_treatment Antibiotics medicine.disease_cause Blood–brain barrier Hippocampus Cellular and Molecular Neuroscience Developmental Neuroscience Daptomycin Streptococcus pneumoniae medicine Animals Rats Wistar Dose-Response Relationship Drug business.industry Meningitis Pneumococcal Brain-Derived Neurotrophic Factor Ceftriaxone medicine.disease Anti-Bacterial Agents Rats Dose–response relationship Disease Models Animal Cytokine medicine.anatomical_structure Neurology Blood-Brain Barrier Immunology Cytokines business Meningitis medicine.drug |
| Zdroj: | Current neurovascular research. 11(3) |
| ISSN: | 1875-5739 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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