Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

Abstract

BackgroundThe hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus.MethodsExperimental meningitis in rats was induced by intracisternal injection of live pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti-pneumococcal antibodies (n = 14). T2 and diffusion weighted MR images were used to analyze changes in hippocampus volume and water diffusion (ADC). The results were correlated to ADC of the cortex, to ventricular volume, and to the extent of hippocampal apoptosis.ResultsBoth ADC and the volume of hippocampus were significantly increased in meningitis rats compared to uninfected controls (Kruskal-Wallis test, p = 0.0001, Dunns Post Test, p < 0.05), and were significantly increased in meningitis rats with an early onset bacteremia as compared to meningitis rats with attenuated bacteremia (p < 0.05). Hippocampal ADC and the volume and size of brain ventricles were positively correlated (Spearman Rank, p < 0.05), whereas no association was found between ADC or volume and the extent of apoptosis (p > 0.05).ConclusionsIn experimental meningitis increase in volume and water diffusion of the hippocampus are significantly associated with accompanying bacteremia.

Meningitis in critically ill patients admitted to intensive care unit for severe community-acquired pneumococcal pneumonia

“…The proportion of patients with pneumococcal bacteremia during their ICU stay was not higher in patients with lumbar puncture than in those without, whereas patients with meningitis had more frequently pneumococcal bacteremia during their ICU stay. This suggests that hematogenous dissemination is probably the main mechanism of meningeal invasion in patients admitted to ICU for severe pneumococcal pneumonia, as previously shown for pneumococcal meningitis in experimental and clinical studies [ 6 , 10 , 25 – 27 ]. We also found that the proportion of patients with a medical history of alcohol abuse was higher in patients with lumbar puncture.…”

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

“…In this study, E. coli was used to induce meningitis, because it is the most frequent gram-negative pathogen of neonatal bacterial meningitis (3). Although brain injury primarily results from local meningeal infection, concomitant systemic bacteremia might aggravate the meningitis-induced disease severity, brain injury, and mortality (9, 13-15). This discordance between disease severity and brain injury means that a poorer outcome does not necessarily lead to increased brain injury (15, 19).…”

“…However, these animal models have certain drawbacks, including small sample size, low infectivity, high mortality, and/or variable extent of brain injury (11). Furthermore, concomitant bacteremia might aggravate the meningitis-induced brain injury (9, 13, 14), thus increasing mortality (8, 9, 15). Therefore, in the present study, we developed a newborn rat model of neonatal bacterial meningitis to mimic the human clinical and neuropathological abnormalities, using 11-day-old newborn Sprague–Dawley rats with titrated intraventricular inoculation of Escherichia coli , the most common gram-negative pathogen of neonatal bacterial meningitis (3).…”

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

“…However, these animal models have certain drawbacks, including small sample size, low infectivity, high mortality, and/or variable extent of brain injury . Furthermore, concomitant bacteremia might aggravate the meningitis‐induced brain injury, thus increasing mortality . Therefore, in the present study, we developed a newborn rat model of neonatal bacterial ventriculitis to mimic the human clinical and neuropathological meningitis, using 11‐day‐old newborn Sprague–Dawley rats, with titrated intraventricular inoculation of Escherichia coli , ( E. coli ) the most common gram‐negative pathogen of neonatal bacterial meningitis .…”