Neurogenin-2 (Ngn2),as a proneural gene that promotes the survival and differentiation of neural precursor cells,is an attractive candidate for therapy against cerebral ischemia-reperfusion injury.However,the delivery approach limits its clinical application.To deliver Ngn2 protein into the cerebral ischemic region and exert a therapeutic effect on injured neurons after ischemia,we here reported that the fusion protein TAT-LBD-Ngn2 was constructed by fusing a transactivator of transcription (TAT) domain and a laminin-binding domain (LBD) to Ngn2.TAT-LBD-Ngn2 promoted the outgrowth of neuronal neurite,increased the survival rate and alleviated apoptosis of hippocampal neurons exposed to oxygen glucose deprivation in vitro.Furthermore,a focal cerebral ischemia model in C57BL/6 mice showed that TAT-LBD-Ngn2 efficiently crossed the blood brain barrier,aggregated in the ischemic zone and was consistently incorporated into neurons.Moreover,TAT-LBD-Ngn2 transduced into brains attenuated neuronal degeneration and apoptosis in the ischemic zone.TAT-LBD-Ngn2 treatment resulted in a reduction of infarct volume that was associated with a parallel improvement in neurological functional outcomes after reperfusion.In conclusion,the targeted delivery of TAT-LBD-Ngn2 into the ischemic zone attenuated cerebral ischemia-reperfusion injury through the inhibition of neuronal degeneration and apoptosis,suggesting that TAT-LBD-Ngn2 is a promising target candidate for the treatment of ischemic stroke.