Erythropoietin can promote survival of cerebral cells by downregulating Bax gene after traumatic brain injury in rats|
Liao, Z. B.; Jiang, G. Y.; Tang, Z. H.; Zhi, X. G.; Sun, X. C.; Tang, W. Y. & Wu, M. J.
Background : Traumatic brain injury (TBI) is an important cause of adult mortality and morbidity. Erythropoietin (Epo) has been shown to promote the viability of cerebral cells by upregulating Bcl-2 gene; however, Epo may exert its antiapoptotic effect via the differential regulation of the expression of genes involved in the apoptotic process.
Aim : The present study examined the neuroprotective effect of Epo as a survival factor through the regulation of the Bax.
Materials and Methods : Wistar rats were randomly divided into three groups: Recombinant human EPO treated (rhEPO) TBI, vehicle-treated TBI, and sham-operated. Traumatic brain injury was induced by the Feeney free-falling model. Rats were killed 5, 12, 24, 72, 120, or 168 h after TBI. Regulation of Bcl-2 was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunofluorescence.
Results : Bax mRNA and protein levels were lower in the rhEPO)-treated rat brains than in the vehicle-treated rat brains. Induction of Bax expression peaked at 24 h and remained stable for 72-120 h in vehicle-treated rat brains, whereas induction of Bax expression was only slightly elevated in rhEPO-treated rat brains. The number of TdT-mediated dUTP Nick-End Labeling(TUNEL)-positive cells in the rhEPO-treated rat brains was far fewer than in the vehicle-treated rat brains.
Conclusions : Epo exerts neuroprotective effect against traumatic brain injury via reducing Bax gene expression involved in inhibiting TBI-induced neuronal cell death.
Bax, cell death, rhEPO, traumatic brain injury