Neuroprotection by a caspase inhibitor in acute bacterial meningitis

Half of the survivors of bacterial meningitis experience motor deficits, se izures, hearing loss or cognitive impairment, despite adequate bacterial ki lling by antibiotics. We demonstrate that the broad-spectrum caspase inhibi tor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-fmk) prevent ed hippocampal neuronal cell death and white blood cell influx into the cer ebrospinal fluid compartment in experimental pneumococcal meningitis. Hippo campal neuronal death was due to apoptosis derived from the inflammatory re sponse in the cerebrospinal fluid. Apoptosis was induced in vitro in human neurons by inflamed cerebrospinal fluid and was blocked by z-VAD-fmk. As ap optosis drives neuronal loss in pneumococcal meningitis, caspase inhibitors might provide a new therapeutic option directed specifically at reducing b rain damage.