Anesthetic-induced neurodegeneration mediated via inositol 1,4,5-trisphosphate receptors.

ABSTRACT: The commonly used general anesthetic isoflurane induces widespread neurodegeneration in the developing mammalian brain through poorly understood mechanisms. We have investigated whether excessive Ca2+ release from the endoplasmic reticulum via overactivation of inositol 1,4,5-trisphosphate receptors (InsP3Rs) is a contributing factor in such neurodegeneration in rodent primary cultured neurons and developing rat brain. We also investigated the correlation between isoflurane exposure and cognitive decline in rats at 1 month of age. Our results show that isoflurane increases cytosolic calcium in the primary cortical neurons through release from the endoplasmic reticulum and influx from the extracellular space. Pharmacological inhibition of InsP3R activity and knockdown of its expression near

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC2846020 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature