Abstract: Objective To investigate the protective effect of cordycepin (COR) on brain tissue damage in rats with cerebral ischemia-reperfusion, and to preliminarily clarify the protectivemechanism. Methods Sixty Wistar rats were divided into 3 groups: Normal control group, modelgroup, and model plus drug group. Detection of learning and memory capacities in rats by step-down test and Y maze test. HE staining was employed to observe the pathological changes of brain tissues. Dry and wet weight ratio was used to calculate brain water content and brain index. TUNEL was used to observe cell apoptosis in brain tissues. The levels of serum SOD, MDA and LDH of rats were determined by ELISA. Western blotting was used to detect the expression levels of Bax / Bcl-2,cleaved cas9 / cas9, cleaved cas3 / cas3, Nrf2, HO-1 and NQO1 proteins. Results Compared withthe model group, COR can dose dependently improve brain tissue damage, inhibit oxidative stress,and promote activation of the Nrf2 / HO-1 / NQO1 pathway. Conclusion Cordycepin can improve brain tissue damage by upregulating the Nrf2 pathway.

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