Journal article
Vancomycin is protective in a neonatal mouse model of Staphylococcus epidermidis-potentiated hypoxic-ischemic brain injury
Antimicrobial Agents and Chemotherapy, Vol.64(3), pp.Art. e2003-19
2019
Abstract
Infection is correlated with increased risk of neurodevelopmental sequelae in preterm infants. In modeling neonatal brain injury, Toll-like receptor agonists have often been used to mimic infections and induce inflammation. Using the most common cause of bacteremia in preterm infants, Staphylococcus epidermidis, we present a more clinically relevant neonatal mouse model that addresses the combined effects of bacterial infection together with subsequent hypoxic-ischemic brain insult. Currently, there is no neuroprotective treatment for the preterm population. Hence, we tested the neuroprotective effects of vancomycin with and without adjunct therapy using the anti-inflammatory agent pentoxifylline. We characterized the effects of S. epidermidis infection on the inflammatory response in the periphery and the brain, as well as the physiological changes in the central nervous system that might affect neurodevelopmental outcomes. Intraperitoneal injection of postnatal day 4 mice with a live clinical isolate of S. epidermidis led to bacteremia and induction of proinflammatory cytokines in the blood, as well as transient elevations of neutrophil and monocyte chemotactic cytokines and caspase 3 activity in the brain. When hypoxia-ischemia was induced postinfection, more severe brain damage was observed in infected animals than in saline-injected controls. This infection-induced inflammation and potentiated brain injury was inoculum dose dependent and was alleviated by the antibiotic vancomycin. Pentoxifylline did not provide any additional neuroprotective effect. Thus, we show for the first time that live S. epidermidis potentiates hypoxic-ischemic preterm brain injury and that peripheral inhibition of inflammation with antibiotics, such as vancomycin, reduces the extent of brain injury.
Details
- Title
- Vancomycin is protective in a neonatal mouse model of Staphylococcus epidermidis-potentiated hypoxic-ischemic brain injury
- Authors/Creators
- J.C.Y. Lai (Author/Creator)P. Svedin (Author/Creator)C.J. Ek (Author/Creator)A. Mottahedin (Author/Creator)X. Wang (Author/Creator)O. Levy (Author/Creator)A. Currie (Author/Creator)T. Strunk (Author/Creator)C. Mallard (Author/Creator)
- Publication Details
- Antimicrobial Agents and Chemotherapy, Vol.64(3), pp.Art. e2003-19
- Publisher
- American Society for Microbiology
- Identifiers
- 991005543956507891
- Copyright
- © 2020 American Society for Microbiology
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.72 Obstetrics & Gynecology
- 1.72.922 Neonatal Hypoxia Effects
- Web Of Science research areas
- Microbiology
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology