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.