BNIP3 and OGD‐induced oligodendrocyte death: Role in white matter injury in cerebral ischemia

Abstract

We sought to identify potential role of BNIP3, a proapoptotic member of the Bcl‐2 family of death‐regulating proteins that promote programmed cell death, in Oxygen–glucose deprivation (OGD) treated primary cultures of rat oligodendrocyte lineage cells (OLs). OGD induced cytotoxic injury to various maturational stages of OLs. Survival assays revealed that oligodendrocyte precursor cells (OPCs) and later‐stage precursors were highly vulnerable, whereas more mature OLs were relatively resistant. Exposure of OLs to OGD resulted in a significant increase in BNIP3 expression. Knockdown of BNIP3 with shRNA reduced OGD‐triggered OL apoptosis. Thirty minutes ischemic preconditioning (IPC) of later‐stage precursors and more mature OLs down‐regulated the BNIP3 expression and shown cytoprotection. Interestingly, OPCs were more susceptible to OGD after IPC pretreatment, concurrent with highly BNIP3 expression. These studies unveil BNIP3 as an important mediator in OLs death and reveal a novel mechanism of action of IPC on stage‐specific OLs cultures, which may contribute to a better understanding of white matter injury in cerebral ischemia.