Abstract: ObjectiveTo investigate the protective effect and possible mechanism of ginkgo diterpene lactone
meglumine (GDLM) on cerebral ischemia-reperfusion (I-R) injury and oxyglucose deprived (OGD) hippocampal neurons.
Methods In vivo experiments: 30 SD rats were divided into sham operation group (Sham), I-R group and GDLM group by
random number table method. GDLM group was injected with GDLM 10 mg/kg by tail vein after I-R modeling, and Sham
and I-R groups were given equal dose of normal saline. The brain tissue was stained with TTC. Hippocampus tissues were
stained by Nissl and TUNEL, and Bradford method was used to quantitatively detect the changes in MDA content, gSH-PX
and SOD activity of hippocampus oxidative stress indexes in 3 groups. In vitro experiments: primary fetal hippocampal
neurons were cultured and divided into control group (Con), OGD/reoxygenation (R) model group and GDLM group. OGD/R
and GDLM groups were treated with oxyglucose deprivation and reoxygenation, while the control group was not treated. The
survival rate of neurons was calculated by MTT assay, apoptosis rate of neurons was measured by TUNEL and Annexin VFITC/PI flow cytometry, and PI3K, pAKt, mTOR protein expression levels were measured by Western blot assay. Results
In vivo experiment: compared with Sham group and I-R group, cerebral infarction volume and apoptosis rate of hippocampal
neurons were significantly reduced in GDLM group, and morphological improvement was significant. MDA expression level
was significantly decreased in GDLM group, while SOD and GSH-PX activities were significantly increased (P＜0.01). In
vitro experiment: compared with OGD/R group, the cell survival rate was increased and apoptosis rate was decreased in
GDLM group, and the expressions of PI3K, pAKt and mTOR were significantly increased (P＜0.01). ConclusionGDLM can inhibit the neuron apoptosis of cerebral ischemia-reperfusion and oxygen-deprived reoxygenated hippocampal
neurons, and has a neuroprotective effect, which may be related to its regulation of PI3K/AKt/mTOR signaling pathway and
oxidative stress.

Key words: reperfusion injury, brain ischemia, bilobalides, neuroprotection, oxidative stress, PI3K/AKt/mTOR
signaling pathway, ginkgo diterpene lactone meglumine