Developing a newborn rat model of ventriculitis without concomitant bacteremia by intraventricular injection of K1 (−) Escherichia coli

Abstract

Background Neonatal meningitis caused by Escherichia coli results in high mortality and neurological disabilities, and the concomitant systemic bacteremia confounds its mortality and brain injury. This study developed an experimental model of neonatal ventriculitis without concomitant systemic bacteremia by determining the bacterial inoculum of K1 capsule‐negative E. coli by intraventricular injection in newborn rats. Methods We carried out intraventricular injections 1 × 102 (low dose), 5 × 102 (medium dose), or 1 × 103 (high dose) colony‐forming units (CFU) of K1 (−) E. coli (EC5ME) in Sprague‐Dawley rats at postnatal day (P) 11. Ampicillin was started at P12. Blood and cerebrospinal fluid (CSF) cultures were performed at 6 h, 1 day, and 6 days after inoculation. Brain magnetic resonance imaging (MRI) was performed at P12 and P17. Survival was monitored, and brain tissue was obtained for histological and biochemical analyses at P12 and P17. Results Survival was inoculum dose‐dependent, with the lowest survival in the high‐dose group (20%) compared with the medium‐ (67%) or low‐ (73%) dose groups. CSF bacterial counts in the low‐ and medium‐dose groups were significantly lower than that in the high‐dose group at 6 h, but not at 24 h after inoculation. No bacteria were isolated from the blood throughout the experiment or from the CSF at P17. Brain MRI showed an inoculum dose‐dependent increase in the extent of brain injury and inflammatory responses. Conclusions We developed a newborn rat model of bacterial ventriculitis without concomitant systemic bacteremia by intraventricular injection of EC5ME.

Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Attenuate Brain Injury in Escherichia coli Meningitis in Newborn Rats

“…Thus, in this study, we aimed to investigate the effect of EVs isolated from MSCs on E. coli -induced neonatal meningitis in an in vivo model. To develop an ideal animal model that mimics the pathophysiology and histopathological characteristics of neonatal bacterial meningitis, we previously tested the intra-cerebroventricular inoculation of E. coli (EC5ME) at a dose of 5 × 10 2 CFU in postnatal day 11 (P11) newborn rats; this dose significantly reduced survival rate and body and brain weight, and induced brain infarction and inflammation and ensuing brain injury, without concomitant bacteremia [ 11 ]. In this study, the previously developed meningitis model was used to evaluate the efficacy of MSC-derived EVs (MSC-EVs).…”

“…However, the efficacy of MSC-derived EVs has not been evaluated in an in vivo neonatal meningitis model. Thus, in this study, we aimed to investigate whether MSC-derived extracellular vesicles (EVs) have therapeutic efficacy via antibacterial, anti-inflammatory, and cell-protective properties in an E. coli -induced neonatal meningitis rat model [ 11 ].…”

Development of a chitosan‐modified PLGA nanoparticle vaccine for protection against Escherichia coli K1 caused meningitis in mice

“…The bacteria enter the brain through the immature barrier and cause meningitis. The other way is to directly inject E. coli K1 into the ventricles of the brain and cause meningitis [ 37 ]. These two models can be used for the investigation of the pathogenesis of E. coli K1 and the evaluation of other therapeutic drug effects but are not suitable for the evaluation of VoNPs and other E. coli K1 vaccines.…”