Cell injury and its protection in astrocytes

Abstract

Incubation of cultured astrocytes in Ca²⁺-containing medium after exposure to Ca²⁺-free medium causes Ca²⁺ influx followed by delayed cell death. Here, we summarize the mechanisms underlying the Ca²⁺-mediated injury of cultured astrocytes and the protective effects of drugs against Ca²⁺-reperfusion injury. Our results show that Ca²⁺-reperfusion injury of astrocytes appears to be mediated by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species (ROS) production, calcineurin, caspase-3, and NF-κB activation are involved in Ca ²⁺-reperfusion injury. Several drugs including T-588 and idebenone protect astrocytes against Ca²⁺-reperfusion injury. The protective effect of idebenone is mediated by nerve growth factor production, whereas that of T-588 is mediated mainly by the mitogen-activated protein/extracellular signal-regulated kinase signal cascade.