摘要Objective: cerebral ischemic/hypox-ic preconditioning (I/HPC) is an endogenous strategy in which brief periods of sublethal ischemia/hypoxia render neural tissues resistant to subsequent ischemic/hypoxic damage. This phenomenon has been found in the brain, heart, liver, intestine, muscle, kidneys, and lung. How-ever, whether HPC has a protective effect on secondary cerebral ischemic injury or protein kinase Cδ (PKCδ) within ischemic patients and animal models is still un-clear. Methods: using a hypoxic preconditioned mouse model and a middle cerebral artery occlusion mouse mod-el, combined with 2,3,5-triphenyl tetrazolium chloride (TTC) staining, SDS-polyacrylamide gel electrophoresis (SDS-PAGE), and Western blot, we observed changes in infarction size, density, edema ratio, and changes in PKCδ and membrane translocation within the ischemic cortex of the middle cerebral artery occlusion (MCAO) mice. Results: HPC can attenuate neurological deficits and cerebral ischemic injuries of mice following MCAO, including decreases in infarct size, edema ratio, densities of infarct area, and neuron loss. In addition, HPC inhib-its PKCδ membrane translocation in the penumbra of the MCAO-induced ischemic cortex. We found that admin-istration of PKCδ-specific inhibitor dV1-1 mimics the neuroprotective effects of HPC, and nonisoform-specif-ic activation of PKC can partially abolish HPC-induced neuroprotection. Ischemic preconditioning decreased the levels of PKCδ in the serum of patients with cerebral in-farction and reduced the cerebral nerve damage caused by ischemia. Conclusion: hypoxic/ischemic precondi-tioning attenuates PKCδ-mediated injury in patients and mice. These findings enrich our understanding of the sig-nal transduction mechanism underlying cerebral HPC and provide clues to developing medicine against ischemia/hypoxia-induced cerebral injuries.