Brain function is severely disturbed in ischemia. Within seconds, consciousness and spontaneous activity is lost, whereas interstitial concentrations of major ions are kept near normal levels. After a few minutes, there is a dramatic increase of potassium and a lowering of sodium, chloride, and calcium concentrations. Similar ionic changes are observed during spreading depression, however, that is spontaneously reversible and may be elicited in the otherwise normally perfused brain. In focal ischemia, the two events occur simultaneously. The central core of very low flow displays the ischemic increase of interstitial potassium concentration, whereas the surrounding tissue exhibits repeated episodes of spreading depression. This may induce energy failure by stimulating metabolism in areas with depressed flow thereby causing cell damage outside the ischemic core.