Ischemia-induced increase in long-term potentiation is warded off by specific calpain inhibitor PD150606

In the present study, the effect of specific, membrane-permeable calpain inhibitor, PD150606, was analysed on synaptic efficacy in in vitro brain slices experiments after ischemic insult of rats in vivo, and on cell viability in a glutamate excitotoxicity test in mouse cell culture. Bilateral common carotid artery ligation (BCCL) for 24 h markedly increased calpain activity and enhanced LTP induction in rat hippocampus, although the CA1 layer significantly shrank. The enhancement of LTP could be diminished by short-term application of PD150606 (40 μM) into the perfusion solution. Intracerebroventricular administration of PD150606 (100 μM) parallel with ischemic insult prevented LTP and effectively inhibited hippocampal calpain activity. Intracerebroventricularly applied PD150606 inhibited the CA1 layer shrinkage after common carotid ligation. High level of exogenous glutamate caused marked decrease of cell viability in mouse cerebellar granule cell cultures, which could be partly warded off by 20 μM PD150606. Our data witness that calpain action is intricately involved in the regulation of synaptic efficacy.