A major emphasis in our group is directed towards understanding the mechanisms of neuroprotection by ischemic preconditioning (IPC) against cerebral ischemia (as elicited by a stroke or cardiac arrest). We have demonstrated in brain that IPC is mediated by two key signaling pathways. One of these pathways is a protein kinase C isozyme epsilon. Another signaling pathway involves the NAD+-dependent class III histone deacetylase SIRT1. Our laboratory is fully engaged in defining how these signaling pathways protect neurons against cell death. We are currently studying how these pathways alter synaptic plasticity and ameliorate mitochondrial function.