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 journalArticlepeer-review

247 Citations (Scopus)


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
Pages (from-to)298-302
Number of pages5
JournalNature Medicine
Issue number3
Publication statusPublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


Dive into the research topics of 'Neuroprotection by a caspase inhibitor in acute bacterial meningitis'. Together they form a unique fingerprint.

Cite this