“…Under these conditions, glycolysis may persist after oxygen has been depleted, but the reduction of oxidative metabolism of glucose leads to decreased ATP levels, while ADP and AMP levels increase (Hertz, 2008), causing a disruption of ionic homeostasis (Hansen, 1985), opening of anion channels (Kimelberg and Mongin, 1998), plasma membrane depolarization (Lipton, 1999), release of glutamate through astrocytic hemichannels (Ye et al, 2003) and downregulation of glutamate transporters (Harvey et al, 2011). The impairment of glutamate transporters, in addition to their operation in the reverse mode, leads to an accumulation of glutamate in the extracellular space (Grewer et al, 2008) and a consequent overactivation of postsynaptic glutamate receptors. Under these conditions, necrotic cell death occurs at the core region, while in the penumbra region the availability of ATP allows a delayed cell death by apoptosis (Broughton et al, 2009).…”