Dipeptidyl peptidase 4 (DPP-4) inhibitors have been shown to have neuroprotective effects in diabetic patients suffering from stroke,but less research has focused on patients with mild hyperglycemia below the threshold for a diagnosis of diabetes.In this investigation,a hyperglycemic mouse model was generated by intraperitoneal injection of streptozotocin and then subjected to focal cerebral ischemia.We demonstrated that the DPP-4 inhibitor linagliptin significantly decreased the infarct volume,reduced neuronal cell death,decreased inflammation,and improved neurological deficit compared with control mice.Linagliptin up-regulated the expression of p-Akt and p-mTOR and regulated the apoptosis factors Bcl-2,Bax,and caspase 9.Taken together,these results suggest that linagliptin exerts a neuroprotective action likely through activation of the Akt/mTOR pathway along with anti-apoptotic and anti-inflammatory mechanisms.Therefore,linagliptin may be considered as a therapeutic treatment for stroke patients with mild hyperglycemia.