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

231 Citations (Scopus)

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

Fingerprint

Cerebrospinal fluid
Bacterial Meningitides
Caspase Inhibitors
Pneumococcal Meningitis
Cerebrospinal Fluid
Apoptosis
Hearing Loss
Audition
Cell death
Ketones
Neurons
Brain
Seizures
Leukocytes
Blood
Cell Death
Cells
Anti-Bacterial Agents
Neuroprotection
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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

Neuroprotection by a caspase inhibitor in acute bacterial meningitis. / Braun, J. S.; Novak, R.; Herzog, K. H.; Bodner, S. M.; Cleveland, J. L.; Tuomanen, E. I.

In: Nature Medicine, Vol. 5, No. 3, 22.03.1999, p. 298-302.

Research output: Contribution to journalArticle

Braun, JS, Novak, R, Herzog, KH, Bodner, SM, Cleveland, JL & Tuomanen, EI 1999, 'Neuroprotection by a caspase inhibitor in acute bacterial meningitis', Nature Medicine, vol. 5, no. 3, pp. 298-302. https://doi.org/10.1038/6514
Braun JS, Novak R, Herzog KH, Bodner SM, Cleveland JL, Tuomanen EI. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nature Medicine. 1999 Mar 22;5(3):298-302. https://doi.org/10.1038/6514
Braun, J. S. ; Novak, R. ; Herzog, K. H. ; Bodner, S. M. ; Cleveland, J. L. ; Tuomanen, E. I. / Neuroprotection by a caspase inhibitor in acute bacterial meningitis. In: Nature Medicine. 1999 ; Vol. 5, No. 3. pp. 298-302.
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