Erythropoietin can promote survival of cerebral cells by downregulating Bax gene after traumatic brain injury in rats.
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.


OBJECTIVE
The present study examined the neuroprotective effect of Epo as a survival factor through the regulation of the Bax.


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.
Liao
Z B
ZB
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. liaozhengbu@hotmail.com
Jiang
G Y
GY
Tang
Z H
ZH
Zhi
X G
XG
Sun
X C
XC
Tang
W Y
WY
Wu
M J
MJ
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D004921:Erythropoietin