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Neuroprotection by a caspase inhibitor in acute bacterial meningitis

Academic Article
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Overview

authors

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

publication date

  • March 1999

journal

  • Nature Medicine  Journal

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.

subject areas

  • Amino Acid Chloromethyl Ketones
  • Animals
  • Antigens, CD18
  • Apoptosis
  • Caspase Inhibitors
  • Cell Line
  • Cysteine Proteinase Inhibitors
  • Hippocampus
  • Humans
  • Male
  • Meningitis, Bacterial
  • Neurons
  • Neuroprotective Agents
  • Pneumococcal Infections
  • Rabbits
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Identity

International Standard Serial Number (ISSN)

  • 1078-8956

PubMed ID

  • 10086385
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Additional Document Info

start page

  • 298

end page

  • 302

volume

  • 5

issue

  • 3

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