Thrombopoietin Has Protective Effect in Neonatal Hypoxia-Ischemia Rat Model

Thrombopoietin (TPO) is a growth factor for the megakaryocytic lineage. The expression of TPO and TPO receptor (c-mpl) in the central nervous system (CNS) and the role of TPO in neural cells and brain damage models were investigated. Our results showed the expression of TPO in human cerebral hemisphere, cerebellum, cerebrospinal fluid and blood plasma. We found that TPO had a protective effect in hypoxic-ischemic rat model, as indicated by the increased ipsilateral brain weight and neuron density in a neonatal rat model of hypoxic-ischemic brain damage. Recoveries of sensorimotor functions and histopathology were observed in these animals that received TPO. In addition, TPO could promote C17.2 cells proliferation by activating PI3K/Akt signaling pathway, and the proliferation could be reduced to nearly basal level by the pre-treatment with LY 294002. The phosphorylation of AKT, which is a hallmark of activation of each molecule was significantly enhanced after the treatment with TPO in the cells, peaking at 30 min after stimulation with TPO. TPO was also found to have an anti-apoptotic effect which mediated via Bcl-2/BAX and suppressing the mitochondrial membrane potential. Results showed the increased level of Bcl-2 and decreased level of BAX were in the time-dependence manner (0, 5, 15, 30 and 60 mins) in these cells. In addition, the mitochondrial membrane potential was significantly decreased by adding 100 ng/ml TPO. Our results indicated that TPO have neural protective effects.