The Effect of S. Pneumoniae Bacteremia on Cerebral Blood Flow Autoregulation in Rats

Abstract

In the present study, we studied the effect of bacteremia on cerebral blood flow (CBF) autoregulation in a rat model of pneumococcal bacteremia and meningitis. Anesthetized rats were divided into five groups (A to E) and inoculated with pneumococci intravenously and normal saline intracisternally (group A, N = 10); saline intravenously and pneumococci intracisternally (group B, N = 10); pneumococci intravenously and pneumococci intracisternally (group C, N = 5); saline intravenously, antipneumococcal antibody intravenously (to prevent bacteremia), and pneumococci intracisternally (group D, N = 10); or saline intravenously and saline intracisternally (group E, N = 10), respectively. Positive cultures occurred in the blood for all rats in groups A, B, and C, and in the cerebrospinal fluid for all rats in groups D and E. Twenty-four hours after inoculation, CBF was measured with laser-Doppler ultrasound during incremental reductions in cerebral perfusion pressure (CPP) by controlled hemorrhage. Autoregulation was preserved in all rats without meningitis (groups A and E) and was lost in 24 of 25 meningitis rats (groups B, C, and D) (P < 0.01). In group A, the lower limit was higher than that of group E (P < 0.05). The slope of the CBF/CPP regression line differed between the meningitis groups (P < 0.001), being steeper for group B than groups C and D, with no difference between these two groups. The results suggest that pneumococcal bacteremia in rats triggers cerebral vasodilation, which right shifts the lower limit of, but does not entirely abolish, CBF autoregulation in the absence of meningitis, and which may further aggravate the vasoparalysis induced by concomitant pneumococcal meningitis.

Cerebral Autoregulation is Influenced by Carbon Dioxide Levels in Patients with Septic Shock

“…Autoregulation of CBF is a sensitive mechanism, which can be impaired by various pathological conditions, and has a direct impact on delayed ischemic events and poor outcome [50,51]. Although cerebral autoregulation was maintained in several experimental models of sepsis [39,44,52,53], most patients with septic shock had impaired cerebral autoregulation in our study. We found only three human studies that have previously evaluated cerebral autoregulation in septic patients, and these yielded conflicting results.…”

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

“…We have previously demonstrated an important role of accompanying bacteremia in experimental pneumococcal meningitis for both mortality [4] and brain pathophysiology (attenuated CSF pleocytosis [2], increased cerebral perfusion pressure and mean arterial pressure as well as an interrupted cerebral autoregulation [3], increased hippocampal apoptosis [5] and increased brain ventricle size, BBB leakage, and white matter apparent diffusion coefficient (ADC) [6]). As described above, there was a positive correlation between hippocampal ADC-values and size of brain ventricles.…”

“…We have previously studied the role of accompanying bacteremia in detail in experimental pneumococcal meningitis and have demonstrated that this complication resulted in an attenuated CSF pleocytosis [2], an interrupted cerebral autoregulation [3], and an increased mortality [4] as well as hippocampal apoptosis [5]. …”

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

“…These findings suggest a possible third, earlier, IL-10-repressible mechanism of neuronal damage, which may precede pneumococcal invasion of the CNS (358). Additionally, in the setting of experimental meningitis, bacteremia has been shown to contribute not only to increased hippocampal apoptosis but also to dysregulation of CBF autoregulation, reduced meningeal inflammation, and attenuated CSF pleocytosis (366,380). The mechanisms involved remain largely unclear.…”