MicroRNAs (miRNAs) have emerged as critical regulators of ischemic stroke, a condition that affects neuronal survival. However, the precise role of miRNAs in regulating neuronal injury during ischemic stroke remains largely unknown. In this study, we investigated the potential role of miR-152-3p in regulating oxygen-glucose-deprivation/reoxygenation (OGD/R)-induced neuronal injury in vitro. We found that OGD/R-exposed neurons expressed less miR-152-3p. Functional analysis revealed that miR-152-3p overexpression increased the viability and reduced the apoptosis and reactive oxygen species (ROS) production of OGD/R-exposed neurons. By contrast, miR-152-3p inhibition exacerbated OGD/R-induced injury. Notably, we identified postsynaptic density protein-93 (PSD-93), an important regulator of neuroprotection during ischemic stroke, as a miR-152-3p target gene. PSD-93 inhibition by small interfering RNA (siRNA) or miR-152-3p reinforced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) antioxidant signaling in OGD/R-exposed neurons. However, PSD-93 overexpression or Nrf2 silencing partially reversed miR-152-3p-mediated neuroprotection in OGD/R-exposed neurons. Overall, these results demonstrated that miR-152-3p protected neurons from OGD/R-induced apoptosis and ROS production by reinforcing Nrf2/ARE antioxidant signaling through targeting and inhibiting PSD-93, findings that suggest miR-152-3p is a potential target for neuroprotection during ischemic stroke. (C) 2019 Elsevier Inc. All rights reserved.