In this study, we used a loss-of-function approach to examine the neuroprotective potential of Npas4 in the context of ischaemic damage. Using oxygen and glucose deprivation, we demonstrated that the knockdown of Npas4 in mouse cortical neurons resulted in increased susceptibility to cell death. The protective effect of Npas4 was further investigated in vivo using a photochemically-induced stroke model in mice. We found a significantly larger lesion size and increased neurodegeneration in Npas4 knockout mice as compared to wild-type mice […] Taken together, these data suggest that Npas4 plays a neuroprotective role in ischaemic stroke by limiting progressive neurodegeneration and neuroinflammation.;Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia […] Npas4, whose expression is robustly and transiently upregulated in the brain during the acute phase of ischaemia, plays a neuroprotective role because Npas4 deficiency increased the susceptibility of cultured neurons to cell death by OGD and exacerbated the severity of brain injury after photochemically-induced stroke in mice.; Reduced Npas4 expression during neural differentiation results in delayed neural differentiation