Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs

Figure 1

Cerebral ischemia induces mitochondrial dysfunction and neuronal cell death. Ischemia-reperfusion induces elevations in cytosolic Ca²⁺ via glutamate binding extrasynaptic NMDA receptors (NMDA-R) and/or mitochondrial-associated membrane (MAM) mediated release from the endoplasmic reticulum (ER). As mitochondrial Ca²⁺ buffering capacity is exceeded and mitochondrial dysfunction ensues, mitochondria produce excessive reactive oxygen species (ROS), decrease capacity for ATP production, and activate the mitochondrial permeability transition pore (MPTP), which can trigger cytochrome c mediated apoptosis. Sustained elevations in cytosolic Ca²⁺ can activate proteases, lipases, and nucleases triggering autophagy or necrotic cell death. NMDA: N-methyl-D-aspartate.