| Osteopontin (OPN), a large secreted glycoprotein with an arginine, glycine, aspartate (RGD) motif, can bind an array of integrins that affect a wide range of cellular processes, such as adhesion, differentiation, survival, and repair. Observation suggested that OPN conferred neuroprotective effects on stroke. Study also showed delayed expression of OPN after focal stroke in rats. We hypothesized that delayed administration of OPN conferred neuroprotective effects on the neonatal hypoxic ischemic (HI) brain injury.Neonatal rats were randomly assigned into 5 groups:Sham group, HI group, OPN group, OPN+GRGDSP group and OPN+Rac1 inhibitor group. Neonatal rats in the Sham group experienced surgical procedure without ligation and those in the remaining groups were subjected to ligation of common carotid artery followed by hypoxia (8% O2) for 2 h. The dose of OPN, GRGDSP and Rac1 was 50 ng,2 ng and 50μg, respectively, and administration was intracerebroventricularly performed at 4, 5 and 6 days after hypoxic injury. Seven and fourteen days after administration, brain atrophy, neurological functions, neurogenesis and angiogenesis were determined. In addition, the VEGF and BDNF expression was detected.At 14 days after OPN treatment, the ratio of right to left brain weight was increased accompanied by decreased spleen to body weight ratio. The wire hanging score was increased 7 days and 14 days after treatment, and the scores for beam balance, cylider test and T maze test were improved 14 days after treatment. Furthermore, after OPN treatment, the number of newly generated neurons and blood vessels was increased at 14 days accompanied by increased expression of VEGF and BDNF. In addition, administration of GRGDSP and Rac1 inhibitor alleviated the neuroprotective effects of OPN.Delayed administration of osteopontin exerted neuroprotective effects on the hypoxic ischemic brain injury via Racl pathway, in which angiogenesis and neurogenesis played important roles.
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