Caspase inhibitors are functionally neuroprotective against oxygen glucose deprivation induced CA1 death in organotypic hippocampal slices

Ray, A., Owen, D., Evans, M.L., Davis, J.B. and Benham, C.D. (2000) Caspase inhibitors are functionally neuroprotective against oxygen glucose deprivation induced CA1 death in organotypic hippocampal slices. Brain Research. pp. 62-69. ISSN 0006-8993
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We have explored the neuroprotective efficacy of the cell penetrant caspase inhibitor, Ac-YVAD-cmk, in a hippocampal slice model of neuronal cell death induced by oxygen and glucose deprivation. Organotypic hippocampal slice cultures were prepared from 8 to 10-day-old rats and maintained for 10 to 12 days in vitro. Pre-treatment with Ac-YVAD-cmk prior to 45 min oxygen and glucose deprivation was neuroprotective as measured by propidium iodide uptake, with an EC50 between 1 and 10 μmol/l. Ac-YVAD-cmk was also able to preserve synaptic function in the organotypic hippocampal slice cultures 24 h after oxygen and glucose deprivation. Ac-YVAD-cmk prevented the increase in histone-associated DNA fragmentation induced by oxygen and glucose deprivation. Interleukin-1β did not reverse the protective effect of Ac-YVAD-cmk, and interleukin-1 receptor antagonist alone was not protective. These results show that caspase inhibitors are neuroprotective in a hippocampal slice culture system, using structural, biochemical and electrophysiological endpoints, and that this effect is not a result of inhibition of interleukin-1β production.

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