Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis

Abstract

Background: Bacteremia and systemic complications both play important roles in brain pathophysiological alterations and the outcome of pneumococcal meningitis. Their individual contributions to the development of brain damage, however, still remain to be defined.

Methods: Using an adult rat pneumococcal meningitis model, the impact of bacteremia accompanying meningitis on the development of hippocampal injury was studied. The study comprised of the three groups: I. Meningitis (n = 11), II. meningitis with attenuated bacteremia resulting from iv injection of serotype-specific pneumococcal antibodies (n = 14), and III. uninfected controls (n = 6).

Results: Pneumococcal meningitis resulted in a significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected controls (0.02 (0.00-0.02), Mann Whitney test, P = 0.0003). Also, meningitis with an attenuation of bacteremia by antibody treatment resulted in significantly reduced apoptosis (0.08 (0.02-0.20), P = 0.01) as compared to meningitis.

Conclusions: Our results demonstrate that bacteremia accompanying meningitis plays an important role in the development of hippocampal injury in pneumococcal meningitis.

Figure 1

Impact of bacteremia on hippocampal apoptosis in experimental pneumococcal meningitis. A. Meningitis controls had significantly lower apoptosis scores* than uninfected controls and than meningitis rats with attenuated bacteremia due to treatment with serotype-specific antibodies (Mann Whitney, P = 0.0003 and P = 0.01, respectively). Bars represent medians. Hippocampal dentate gyrus histology showed sporadic occurrence of apoptotic cells (arrowhead) in rats with attenuated bacteremia (B+C) as compared to meningitis controls having a higher number of apoptotic cells (D+E). * Appearance of apoptotic cells were counted in 4 different slices spanning the hippocampus (3 visual fields in each of the two blades of the dentate gyrus). Each visual field was judged according to the following score: 0-5 cells = 0; 6-20 cells = 1; > 20 cells = 2. A mean value per animal was calculated from all inspected fields (48 fields per animal).