Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo.

Neuroprotective strategies using diazoxide (DZX) have been demonstrated to limit ischemia/reperfusion (I/R)‑induced injury and cell apoptosis. In type 2 diabetes mellitus, DZX has been reported to improve β‑cell function and reduce their apoptosis, through suppressing endoplasmic reticulum (ER) stress. However, the effects of DZX on ER stress during I/R‑induced neuronal apoptosis in the hippocampus remains to be elucidated. In the present study, pretreatment of hippocampal neurons with DZX was revealed to inhibit oxygen‑glucose deprivation (OGD)‑stimulated apoptosis in vitro and to alleviate I/R‑induced hippocampal injury and behavioral deficits in rats in vivo. Furthermore, OGD and I/R were demonstrated to induce ER stress via upregulating the expression of ER stress‑associated proteins, including C/EBP homologous protein, 78 kDa glucose‑regulated protein and caspase‑12, whereas the exogenous administration of DZX effectively downregulated ER stress‑associated protein expression following OGD and I/R. In addition, DZX was revealed to significantly increase the protein expression of B‑cell lymphoma (Bcl)‑2 and suppress the expression of caspase‑3 and Bcl‑2‑associated X protein. These findings suggested that DZX may protect cells against apoptosis via regulating the expression of ER stress‑associated proteins in vitro and in vivo, thus enhancing the survival of hippocampal cells. The present results suggested a novel mechanism that may underlie the protective effect of DZX administration in the central nervous system.