Reduction of intracranial pressure by nimodipine in experimental pneumococcal meningitis

OBJECTIVE: In this study, we investigated the effect of the calcium channel blocker nimodipine on the pathophysiologic alterations during experimental pneumococcal meningitis in rats. DESIGN: Prospective, controlled trial. SETTING: University center, animal laboratory. SUBJECTS: A total of 37 adult male Wistar rats (290-360 g). INTERVENTIONS: Meningitis was induced by the intracisternal injection of pneumococci. Anaesthetized animals were treated with nimodipine (30 microg/kg/hr iv) either 15 mins before (pretreatment) or 5 hrs after (posttreatment) pneumococcal challenge. MEASUREMENTS AND MAIN RESULTS: Treatment with nimodipine (30 microg/kg/hr iv) significantly decreased the pneumococci-induced rise in intracranial pressure irrespective of the time of administration. Moreover, pretreament with nimodipine also significantly reduced the pneumococci-induced increase in cerebrospinal fluid white blood cell counts. To ascertain possible mechanisms of the beneficial effect, we investigated the influence of nimodipine on reactive oxygen species (ROS) and cytokine production. By using lucigenin-enhanced chemiluminescence, we found that nimodipine inhibited the pneumococci-induced production of ROS in human whole blood samples. Moreover, nimodipine significantly reduced the pneumococci-induced increase in the interleukin-6 concentrations in the cerebrospinal fluid. CONCLUSION: Our results demonstrate that nimodipine decreases the intracranial pressure during experimental pneumococcal meningitis, possibly by mechanisms including the reduction of ROS and interleukin-6 production.