Fig. 3

Calcium overload and the calcineurin/cyclophilin D signal transduction pathway for the cell death induced after cerebral ischemia. Ischemia induces the loss of ATP-dependent ion homeostasis and leads to an increase in intracellular Na⁺ and extracellular K⁺. Eventually, the cells undergo depolarization. As a result, excessive Ca²⁺ influx due to the activation of voltage-sensitive calcium channels, NMDA, and AMPA receptors activates numerous signal transduction cascades, particularly the calcineurin/cyclophilin D signal transduction pathway. This eventually induces the MPT, leading to mitochondrial dysfunction