Abstract: Objective To investigate the effects of recombinant human erythropoietin (rhEPO) on angiogenesis and neurofunction recovery of mice with traumatic brain injury(TBI). Methods Mice were randomly divided into sham operation group (sham group), traumatic brain injury group (TBI group, severe TBI model made by controlled cortical impact) and rhEPO treatment group (EPO group, rhEPO intraperitoneal injected at 5 000 IU/(kg·d) for 7 days after the trauma). Each group included 15 mice. Neurological scores were performed at 3, 7, and 14 d using modified neurological severity score(mNSS). Fourteen days after injury, Western blot and immunofluorescence were used to detect the protein expression of eNOS, VEGF and CD31 around ipsilateral cerebral cortex, and the microvessel density (MVD) was detected by CD31⁺ cells. The lesion volume was measured at 21 d after injury using hematoxylin-eosin (HE) stained specimens. Results 3,7 and 14 d after TBI, mNSS of TBI group was signifi- cantly higher than that of sham group (P＜0.001). 7 and 14 d after TBI, mNSS of EPO group was lower than those of TBI group (P＜0.05). Fourteen days after TBI, the protein expression of eNOS, VEGF and CD31 was higher in TBI group than those of sham group, and the EPO group was higher than those of TBI group. (P＜0.05). 14 d after TBI, the MVD of TBI group was significantly lower than sham group(P＜0.001), and the MVD of EPO group was significantly higher than TBI group(P＜0.001). Twenty one days after injury, the volume of EPO group was reduced compared with TBI group (8.90±1.79) (P＜0.05). Conclusions rhEPO promotes angiogenesis and improves neurological function after TBI of mice.

Key words: erythropoietin, traumatic brain injury, angiogenesis, eNOS, VEGF