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

Abstract

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 meningitis without concomitant systemic bacteremia by determining the bacterial inoculum of K1 capsule-negative E. coli by intraventricular injection in newborn rats. Meningitis was induced by intraventricular intraventricular injection of 1 x 102 (low dose), 5 x 102 (medium dose), or 1 x 103 (high dose) colony forming units (CFU) of K1 (-) E. coli (EC5ME) in Sprague-Dawley rats at postnatal day 11. Ampicillin was started at postnatal day 12. 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 postnatal days 12 and 17. Survival was monitored, and brain tissues were obtained for histological and biochemical analyses at P12 and P17. Survival was inoculum dose-dependent, with lowest survival in high dose group (20�x0025;) compared with medium (80%) or low (70%) dose group. CSF bacterial counts in low and medium dose group were significantly lower than that in 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 postnatal day 17. Brain MRI showed an inoculum dose-dependent increase in the extent of ventriculomegaly, cerebral infarct, extent of brain injury, and inflammatory responses. We developed a newborn rat model of bacterial meningitis without concomitant systemic bacteremia by intraventricular injection of K1 (-) E.coli.