PTEN is the only suppressor genes on the dual phosphatase activity of tumor in recent years, It is the most important tumor suppressor gene after p53 era.PTEN focus on the autosome 10q23.3, with the activity of lipid phosphatase and protein phosphatase.Normaly, there are three signaling pathways for PTEN to play a role in regulating cells growth, apoptosis, migration and transformation: PI3K/AKT, FAK and MAPK.A study on the central optic nerve injury model,found that PTEN-mediated restrain the activity of mTOR is a key endogenous inhibitory mechanisms affect CNS axonal regrowth after injury.Others found that PTEN can reduce infarct volume and neuronal apoptosis through pharmacological and genetic interference inhibition in the acute cerebral ischemia, and it is proved that through activated AKT/mTOR/S6 signal pathway to achieve neuroprotection.But is it true that PTEN signaling pathway is the inhibitory mechanisms for CNS axonal regrowth of ischemic stroke? There is no systematic report of suppressant PTEN can promote recovery after ischemic.In the views above, this paper aimed to investigate the effects of PTEN inhibition on the axonal regrowth and functional recovery of ischemic stroke and try to explore its downstream molecular mechanism.Objectives: Study on the effect of PTEN inhibitor bpv on the axonal regrowth and functional recovery of cerebral ischemia reperfusion injury in mice, and explore whether PTEN is the endogenous inhibition mechanism of the axonal regrowth after stroke.Methods: Firstly, according to the modified Zea-Longa suture method, build MCAO-reperfusion injury model.Cerebral ischemia and reperfusion, at the time point of ld, 3d, 7d, 14d, Cortical and striatal tissue were harvested from ischemic boundary zones and contralateral separately, use Western-blot technique to detect the p-PTEN and PTEN proteins expression at each time point of each group.Secondly, the animals were randomly divided into 3 groups: Sham group; MCAO + saline group; MCAO+ bpv group.a potent PTEN inhibitor bpv at the doses of 0.2mg/kg/daily via a intra-peritoneal route for 14 days, starting at 24 hours after reperfusion;.MCAO+Saline is injected with the same dose of saline.After 96h, we use TTC staining and compare each groups cerebral infarction volume, observe the mortality of animals after 14 days ischemia and the cortical width index at the time point: ld, 3d, 5d, 7d, 9d, 14d, we use NSS and forelimb placement test to assess the changes of neurological function in each group.We use Bielschowsky Silve staining method to show the distribution of axons within the white matter tracts at the edge of the cerebral ischemia, we use IHC to detect MBP and protein-43s (GAP-43) expression which is associated with growth on the ischemic border zone.Results: During the animal ischemia reperfusion 1-14 days, total PTEN protein showed persistent high levels of expression in the ischemic cortex and striatum, no significant decrease compared with the Sham; Also no significant changes on cerebral ischemia phosphorylation of PTEN proteins (non-activated) level compared with the Sham, the levels of phosphorylated and total PTEN protein expression, also its ratio in the contralateral cortex and striatum, compared with the Sham, have no significant changes(P>0.05).After 96h ischemia and reperfusion, there is no infarct area in Sham, the Saline groups infarct volume was 18.75% ± 1.69%; the bvp treated groups infarct volume was 18.65% ± 1.54%, no significant difference between these two groups (P>0.05).After 14d ischemia reperfusion, the mortality of bpv group was 28.57%, Saline group is 52.38%, more than the bpv treated group (P<0.05).Compared the neurological score within bpv treatment group and Saline group at each time point, the nerve injury severity score of 1 lds 4.33± 1.07 vs 5.83 ± 1.7 (P<0.05), 14ds 3.58 ± 0.9 vs 5.33 ± 1.37 (P<0.01); forelimb placement test score of 11ds 0.58 ± 0.51 vs 1.17 ± 0.57 (P<0.05), 14ds 0.50 ± 0.52 vs 1.17 ± 0.57 (P <0.01).Compared bpv treatment group with Saline group, ischemia-reperfusion 14d cerebral cortex width index is 0.68 ± 0.13 vs 0.56 ± 0.14 (P<0.05), Bielschowsky Silver staining positive area is 35.41%± 2.08% vs 24.77% ± 4.31% (P<0.001), MBP protein positive area of the ischemic border zone is 32.10% ±4.53% vs 27.01% ± 4.79% (P <0.05), GAP-43 positive cells is 51.77 ± 6.75 vs 34.35±4.06 (P <0.001).Conclusions:Maybe the activated PTEN is the endogenous factor to inhibit axonal regrowth after cerebral ischemia;Maybe the PTEN signaling pathway is the important endogenous inhibit mechanism for axonal regrowth.;PTEN inhibition can significantly reduce the mortality of cerebral ischemia reperfusion injury in mice, promote CNS axonal regrowth and functional recovery.Exclude the possibility of bpv promotes functional recovery of mice by reducing the infarction volume.