Objectives: To study whether the PTEN inhibitors bpv ischemia increase AKT and mTOR activity post-ischemic, as well as promotes neurite outgrowth on primary cortical neurons in vitro OGD model, To investigate the PTEN inhibitions downstream molecular mechanisms in the promotion of CNS axonal regrowth after ischemic stroke.Methods: A potent PTEN inhibitor bpv at the doses of 0.2mg/kg/daily via a intra-peritoneal routes, starting at 24 hours after reperfusion;At the time point 96h after reperfusion, Cortical and striatal tissue were harvested from ischemic boundary zones (IBZ)and contralateral of the bpv treatment group and Saline group, use Western-blot to detect protein expression of AKT, p-AKT, S6,p-S6.Isolated from mouse embryos, cultured primary cortical nerve cells, after 7 days, 1h OGD to the neurons, then divided into five groups: 200niM bpv group, 100nM bpv treatment group, 50nM bpv treatment group, 20nM bpv group and 2μl Saline group.They are placed in a CO2 incubator, After 24 hours re-oxygenation, immunostaining was performed using antibodies against TUJ1 to assess dendrite outgrowth under the fluorescence microscope, determine the dose of bpv promote neurite outgrowth of neurons after OGD.After that, processing 1h OGD to neurons, then divided into four groups: bvp +mTOR inhibitor (rapamycin-100nM) group, bpv+AKT inhibitors (LY294002, 10μM), bpv+DMSO and Saline group.They are placed in a CO2 incubator, After 24 hours re-oxygenation, immunostaining was performed using antibodies against TUJ1 to assess dendrite outgrowth under the fluorescence microscope, determine PTEN inhibition promote ischemic downstream molecular mechanism of CNS axonal regrowth after stroke.Results: The bpv group significantly increased phosphorylation of AKT and S6 in the Cortical and striatal IBZ at 96h after reperfusion compared to saline injection.After 24h re-oxygenation, the neurite length is 200.51 ±35.98um in 100riM bpv group, much higher than the others (P <0.001).After 24h re-oxygenation, the neurite length is 210.80 ± 49.34um in bpv+DMSO group,much higher than bpv+mTOR inhibitor group (141.22 ± 25.15um) and bpv+AKT inhibitor group (140.46 ±26.16um) (P<0.001).The neurite length of Saline group is 164.10 ± 24.60um, also much higher than the bpv + mTOR inhibitor group and bpv + AKT inhibitor group (P <0.001).There is no difference of the neurite length between bpv + mTOR inhibitor group and bpv + AKT group (P>0.05).Conclusion: The PTEN inhibitors bpv promotes neurite outgrowth on primary cortical neurons in vitro OGD model that is probably through activated AKT/mTOR signal pathway.Maybe the activation of AKT/mTOR/S6 is the main downstream molecular mechanisms of PTEN inhibition promote CNS axonal regrowth after ischemic stroke.