Protective mechanisms of calorie restriction against neuronal cell death in stroke. Stroke acts in detriment of neuronal health by different mechanisms, including exicitotoxicity, calcium overload, oxidative stress and inflammation, which can culminate in neuronal apoptosis. CR prepares neurons to bear each of these forms of stress by modifying the levels of key stress-response proteins. Certain proteins are up-regulated, such as the chaperones GRP78 and Hsp70, which protect from calcium overload and inflammation; neurotrophic factors such as BDNF, whose role is to protect the cells from excitotoxicity but are also key promoters of neurogenesis after stroke; SIRT1, a central mediator of many CR beneficial effects such as resistance to oxidative stress and moderation of inflammation (through its down-regulation of NFB); UCPs, which are thought to decrease the generation of ROS; and HO-1, with anti-oxidant properties. Hence, CR prepares brain cells at many levels to resist stroke-induced neuronal cell death and promote recovery after stroke.