Caspases inhibition decreases neurological sequelae in meningitis.

Abstract

To evaluate the effects of sustained caspase inhibition during the acute phase of meningitis-induced brain injury. Changes in neurobehavioral performance were the primary outcome variables. Randomized prospective animal study. University research laboratory. Male Wistar rats. Animals underwent a basilar cistern inoculation of group B Streptococci to induce meningitis. Sixteen hours later animals were randomized to receive Bocaspartyl (OMe)-fluoromethyketone (BAF) for 4 days or placebo in addition to antibiotic therapy. The assessment of neurobehavioral performance was started 7 days after initiation of treatment and continued for the following 3 wks. A subgroup underwent early kill, at 5 days, to evaluate caspase 3 activity in brain tissue. There was a group of Sham instrumented animals. BAF decreased caspase 3 activation in meningitic animals. There were no significant motor deficit differences between the infected groups. Cognitive performance was significantly improved in the BAF group. These findings demonstrate that sustained systemic administration of BAF inhibits caspase 3 activation and decreases neurologic sequelae in a rat model of bacterial meningitis.