NAD+ and NADH play crucial roles in a variety of biological processes including energy
metabolism, mitochondrial functions, and gene expression. Multiple studies have indicated that NAD+
administration can profoundly decrease oxidative cell death as well as ischemic and traumatic brain injury,
suggesting NAD+ metabolism as a promising therapeutic target for cerebral ischemia and head injury.
Cumulating evidence has suggested that NAD+ can produce its protective effects by multiple mechanisms, including
preventing mitochondrial alterations, enhancing energy metabolism, preventing virtually all forms of cell death including
apoptosis, necrosis and autophagy, inhibiting inflammation, directly increasing antioxidation capacity of cells and tissues,
and activating SIRT1. Increasing evidence has also suggested that NADH metabolism is a potential therapeutic target for
treating several neurological disorders. A number of studies have further indicated that multiple NAD+-dependent enzymes
such as sirtuins, polymerase(ADP-ribose) polymerases (PARPs) and CD38 mediate cell death and multiple biological
processes. In this article, an overview of the recent findings regarding the roles of NAD+/NADH and NAD+-
dependent enzymes in cell death and ischemic brain injury is provided. These findings have collectively indicated that
NAD+/NADH and NAD+-dependent enzymes play fundamental roles in oxidative stress-induced cell death and ischemic
brain injury, which may become promising therapeutic targets for brain ischemia and multiple other neurological disorders.