However, the sources of wild Rhodiola rosea L are on the edge of exhaustion. Therefore, considerable effort has been devoted to the synthesis and structure modification of salidroside. Our group synthesized a salidroside analog 2-ethyl-2-acetamido-2-deoxy-b-D-pyranoside and showed that it has pharmacological properties including antioxidation and anti-apoptosis, and its protective effects was shown to be superior to that of salidroside. In order to provide a new window into the pharmacological properties of GlcNAc-Sal, the present study was designed to investigate neuroprotective effects of GlcNAc-Sal on OGD-Rinduced HT22 cell death in vitro and GCI-R-induced hippocampal damage in vivo and further explored the underlying mechanisms. We hope to expand the understanding of the potential therapeutic value of salidroside for cerebral ischemia injury. Previous study showed that, GlcNAc-Sal pretreatment significantly inhibited cell apoptosis, here we further demonstrate the neuroprotective properties of GlcNAc-Sal pretreatment in the cultured hippocampal cells as well as in mice subjected to ischemia-reperfusion injury. Immortalized neuronal HT22 cells is a subclone of HT4, originating from mouse hippocampus. First we investigated the neuroprotective properties of GlcNAc-Sal in cultured HT22 cells. Pretreatment with GlcNAcSal, which had no significant effect on cell viability under normal conditions, reversed the injury induced by OGD-R in a concentration-dependent manner. Then, we examined the protective effects of GlcNAc-Sal in vivo using a model of transient global cerebral ischemia in mice induced by a 1 h BCCAO and 4 h reperfusion, and histochemical HhAntag691 studies revealed that GlcNAcSal inhibited the neuronal damage induced by GCI-R. Taken together, our findings clearly indicated that GlcNAc-Sal pretreatment has neuroprotective effects, which prompted further investigation of the underlying mechanisms. Whether treatment with GlcNAc-Sal during or after the induction of OGD-R or GCIR has protective effects remains uncertain and requires further study. OGD-R model, a highly reproducible and appropriate in vitro model of ischemic stroke, is believed to better mimic the pathological conditions of stroke including excitotoxicity, oxidative stress, intracellular calcium overload, inflammation and apoptosis. In this study, morphological examinations indicated that exposure to OGD-R led to extensive apoptotic-like cell death in HT22 cells. These results are consistent with the previously reported findings that stimulation with OGD-R induces neuronal death in a prevailing form of apoptosis under in vitro conditions. Apoptosis, which plays a significant role in the pathophysiology of cerebral ischemia reperfusion injury, occurs via a cascade of cellular events involving several apoptosis-regulatory genes, which are induced in apoptotic cells. The Bcl-2 family proteins represent a critical checkpoint in major apoptotic signal transduction cascades, acting upstream of irreversible damage to cellular constituents. The Bcl-2/Bax ratio is a determining factor in the regulation of apoptotic cell death.