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

Abstract

Background: The 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.

Methods: Experimental 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.

Results: Both 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).

Conclusions: In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly associated with accompanying bacteremia.

Figure 1

T2W images showing placement of the ROI delineating the hippocampus and specifically the dentate gyrus in the rat brain. The ROI was placed on two consecutive coronal brain slices. A mean ADC was measured using MIPAV.

Figure 2

Association between hippocampal ADC and hippocampal volume (a) and hippocampal apoptosis (b). ADC of hippocampus was significantly correlated to volume (Figure 2a) in meningitis rats (Spearman Rank ρ = 0.75, p = 0.009) and in meningitis rats with early onset bacteremia (ρ = 0.65, p = 0.043), but not of statistical significance in meningitis rats with an attenuated bacteremia (ρ = 0.42, p = 0.14). No correlation between hippocampus ADC and apoptosis was observed (Figure 2b, p > 0.05).