Neuroprotection by a caspase inhibitor in acute bacterial meningitis

J. S. Braun, R. Novak, K. H. Herzog, S. M. Bodner, J. L. Cleveland, E. I. Tuomanen

Research output: Contribution to journalArticle

233 Scopus citations

Abstract

Half of the survivors of bacterial meningitis experience motor deficits, seizures, hearing loss or cognitive impairment, despite adequate bacterial killing by antibiotics. We demonstrate that the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-fmk) prevented hippocampal neuronal cell death and white blood cell influx into the cerebrospinal fluid compartment in experimental pneumococcal meningitis. Hippocampal neuronal death was due to apoptosis derived from the inflammatory response in the cerebrospinal fluid. Apoptosis was induced in vitro in human neurons by inflamed cerebrospinal fluid and was blocked by z-VAD-fmk. As apoptosis drives neuronal loss in pneumococcal meningitis, caspase inhibitors might provide a new therapeutic option directed specifically at reducing brain damage.

Original languageEnglish (US)
Pages (from-to)298-302
Number of pages5
JournalNature medicine
Volume5
Issue number3
DOIs
StatePublished - Mar 22 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Braun, J. S., Novak, R., Herzog, K. H., Bodner, S. M., Cleveland, J. L., & Tuomanen, E. I. (1999). Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nature medicine, 5(3), 298-302. https://doi.org/10.1038/6514