Caspases inhibition decreases neurological sequelae in meningitis

Jose Irazuzta, Robert K. Pretzlaff, Basilia Zingarelli

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

OBJECTIVE: 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. DESIGN: Randomized prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSION: These findings demonstrate that sustained systemic administration of BAF inhibits caspase 3 activation and decreases neurologic sequelae in a rat model of bacterial meningitis.

Original languageEnglish (US)
Pages (from-to)1603-1606
Number of pages4
JournalCritical Care Medicine
Volume36
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • Brain injury
  • Caspase 3
  • Meningitis
  • Neurobehavioral performance

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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