Figure 2.

Schematic representation of the mitochondrial mechanisms involved in neuronal cell death following cerebral ischemia. Mitochondrial dysfunction has been shown to be a critical player in mediating ischemic neuronal cell death via either necrosis or apoptosis. During cerebral ischemia, the absence of glucose and oxygen causes exacerbated intracellular and mitochondrial calcium (Ca²⁺) uptake, leading to mitochondrial dysfunction and bioenergetic failure. The extensive Ca²⁺ accumulation by mitochondria has been shown to increase the susceptibility to mitochondrial permeability transition pore (MPTP) opening, favoring reactive oxygen species (ROS) formation, mitochondrial membrane potential (ΔΨm) collapse, mitochondrial swelling, and rupture of the mitochondrial outer membrane. MPTP opening can also trigger the release of pro-apoptotic proteins, leading to neuronal cell death by apoptosis.