Objective To improve a model of hypoxic-ischmic brain injury (HIBI) in neonatal rats and observe the effects of hypoxic-ischemic brain injury on cerebral pathology and neurotrophic factor. Methods Thirty-two healthy 7-day-old neonatal Sprague-Dawley (SD) rats were used as research subjects and randomly divided into 3 groups:the control group (n=5), the sham operated group (n=8), and the HIBI group (n=19). The rats in the HIBI group received hypoxia immediately after operation without previous anaesthesia. The body weight, behavioral ability and neuropathological changes in each group were observed. β-NGF and human-NT3 of the brain tissue in the sham operated and HIBI groups were compared on d3 and d14. Results (1) The body weight gain of the HIBI group was significantly slower and lower than that in the control group and sham operated group (P<0.01). (2) Behavioral abnormalities were found in all rats of the HIBI group including unable to turnover (84%), muscle tremor and/or head tremble (63%) and mortality (21%). (3) HE staining showed neuronal damages and proliferation of neuroglial cells in the left hemisphere of the HIBI group. (4) The concentration of human-NT3 in the HIBI group was increased than that of sham operated group, but the concentration of β-NGF was not significantly different from that in the two groups on d3. ConclusionsA neonatal rat model of HIBI is successfully established and it is more closely resembling the course of human neonatal HIBI. The increase of neurotrophic factor plays an important role in the neuroprotection mechanism in the early phase of HIBI.