Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia

Abstract

Mitochondria play important roles as the powerhouse of the cell. After cerebral ischemia, mitochondria overproduce reactive oxygen species (ROS), which have been thoroughly studied with the use of superoxide dismutase transgenic or knockout animals. ROS directly damage lipids, proteins, and nucleic acids in the cell. Moreover, ROS activate various molecular signaling pathways. Apoptosis-related signals return to mitochondria, then mitochondria induce cell death through the release of pro-apoptotic proteins such as cytochrome c or apoptosis-inducing factor. Although the mechanisms of cell death after cerebral ischemia remain unclear, mitochondria obviously play a role by activating signaling pathways through ROS production and by regulating mitochondria-dependent apoptosis pathways.

Mitochondrial dynamics in neuronal injury, development and plasticity

“…In vitro models of cerebral ischemia confirm these findings, as glutamate excitotoxicity (Kumari et al, 2012;Niizuma et al, 2010) and hypoxia (Sanderson et al, 2015) on their own can induce mitochondrial fragmentation. The relationship between mitochondrial fission and ischemic injury appears more than correlative, as inhibition of Drp1 with the small-molecule inhibitor mdivi-1 was shown by several groups to decrease infarct volume following MCAO (Grohm et al, 2012;Li et al, 2015;Zhang et al, 2013).…”

The Role of Parl and HtrA2 in Striatal Neuronal Injury After Transient Global Cerebral Ischemia

“…3,4 Mitochondrial dysfunction also plays a pivotal role in ischemic neuronal injury, and maintaining mitochondrial integrity against cerebral ischemia is a very important cellular response. [5][6][7] The presenilin-associated rhomboid-like (PARL) protein is a member of the rhomboid family and is located in the inner mitochondrial membrane. As with other rhomboids, PARL is an intramembrane serine protease.…”

Diabetes-Mediated Exacerbation of Neuronal Damage and Inflammation After Cerebral Ischemia in Rat: Protective Effects of Water-Soluble Extract from Culture Medium of Ganoderma lucidum Mycelia

“…In particular, reperfusion after a long period of vessel occlusion triggers explosive generation of ROS, which causes cell death by peroxidative damage of lipids, proteins and nucleic acids (Warner et al, 2004;Anabela et al, 2006). In addition to the early necrotic cell death in the ischemic core region, ROS triggers apoptosis, a delayed death of cells, in the ischemic penumbra (Nakka et al, 2008;Niizuma et al, 2010). Furthermore, ROS induces rupture of blood brain barrier through transcriptional activation of matrix metalloproteinase and pro-inflammatory cytokines resulting in the extension of cerebral infarction and exacerbation of brain edema (Cunningham et al, 2005;Zhao et al, 2006).…”