Fig. 2. Overview of the pathogenesis of hypoxic–ischemic brain injury. Excitotoxic brain injury after hypoxic–ischemia occurs because of overstimulation of neurons after excess glutamate release. Influx of sodium and calcium leads to cellular depolarization and swelling and activation of multiple injury cascades that lead to cell death. Critical mediators include the generation of free radicals and activation of enzymes that leads to membrane damage, inflammation, and apoptosis. Mitochondrial energy failure and calcium overload further contribute to the generation of free radicals and stimulation of apoptotic cascades through the release of cytochrome C .