Calpain inhibitors improve the recovery of synaptic transmission from hypoxia in hippocampal slices.

Two inhibitors of calcium activated proteases (calpains) were tested for their effects on hypoxia-induced synaptic dysfunction in hippocampal slices. Hypoxic episodes lasting for either one or two minutes beyond the point at which action potentials (fiber volleys) disappeared were used. Leupeptin and calpain inhibitor I had no reliable effects on the rate at which synaptic transmission declined during hypoxia or the time required for loss of action potentials, but both drugs did substantially improve the degree of recovery. Moreover, the percentage of slices meeting an arbitrary criterion for viability after hypoxic treatment was greatly increased by the drug treatment. These results point to the conclusion that proteolysis triggered by calcium influx during hypoxia contributes to pathophysiology.