Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission

• NRG1 protects against OGD-induced cortical neuronal apoptosis.
• NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition.
• GABA receptor agonists have no synergistic effect with NRG1.
• NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists.
• The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.

Identifying novel neuroprotectants that can halt or even reverse the effects of stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is an effective neuroprotectant, but its molecular mechanisms are largely unclear. In this study, NRG1 rescued cortical neurons from oxygen-glucose deprivation (OGD) model, but the effect was blocked by neutralizing NRG1 and ErbB4 inhibition. In addition, γ-Aminobutyric acid (GABA) receptor agonists had no synergistic effect with NRG1, and the neuroprotective effect of NRG1 against OGD was partly blocked by GABA receptor antagonists. Importantly, NRG1 neuroprotection against brain ischemia was abolished in the mice with specific deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1 protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic transmission.