In summary, this study for the first time demonstrates that NADPH oxidase-mediated HDAC4/5 expression and activity contribute to cerebral ischaemia injury via HMGB1 signalling pathway, suggesting a new pathogenic pathway governing cellular responses to ischaemic stress, which may provide an important therapeutic strategy to prevent tissue damage in ischaemic stroke. This evidence concerns the gene HMGB1 and ischemic stroke.