Effect of Recombinant Human Erythropoietin on Survivin Expression in Brain Tissues after Traumatic Brain Injury in Rats

Peng Lei, Longfeng Peng, Xingchao Zhang

Department of Neurosurgery, Lanzhou General Hospital, Lanzhou, China.

DOI: 10.4236/ss.2012.35053                

Abstract

Objective: To explore the regulative effect on Survivin of r-HuEPO after traumatic brain injury (TBI) in rats, and understand the neuroprotection mechanisms of r-HuEPO. Methods: Seventy-eight adult Wistar rats were randomly divided into sham operation group (n = 6), TBI group (n = 36) and r-HuEPO group (n = 36). The experimental TBI model was created by Feeney’s method. Samples were obtained after injury for measuring apoptosis of cells by Epics XL Flow Cytometer. Immunochemical method was performed for inspection of expressions of Survivin and NF-κB proteins. Results: Compared to the sham group, the number of apoptotic cells and Survivin, NF-κB immunopositive cells was significantly increased in the injured brain after TBI (P < 0.01). R-HuEPO significantly increased the expression of survivin and NF-κB, but decreased the apoptotic rates. Conclusion: Increased expression of NF-κB by r-HuEPO may play important role in regulating Survivin level, inhibiting neuronal apoptosis in cortex and exerting protective function to neurons.

Keywords

Recombinant Human Erythropoietin (r-HuEPO); Brain Injury; Survivin; NF-κB; Apoptosis

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	E. A. Johnson, S. I. Svetlov, K. K. Wang, et al., “Cell-Specific DNA Fragmentation May Be Attenuated by a Survivin-Dependentmechanism after Traumatic Brain Injury in Rats,” Experimental Brain Research, Vol. 167, No. 1, 2005, pp. 17-26. doi:10.1007/s00221-005-2362-2
[2]	I. Yatsiv, N. Grigoriadis, C. Simeonidou, et al., “Erythropoietinis Neuroprotective, Improves Functional Recovery, and Reducesneuronal Apoptosis and Inflammation in a Rodent Modelof Experimental Closed Head Injury,” FASEB Journal, Vol. 19, No. 12, 2005, pp. 1701-1703.
[3]	J. Y. Jiang and C. Z. Luo, “Modern Brain Injury,” The Second Military Medical University, Shanghai, 2004, pp. 417-419.
[4]	P. Lei, L. Z. Tian, Y. Wang, et al., “General Treatment for Severe Brain Injury,” Chinese Journal of Trauma, Vol. 21, No. 7, 2005, pp. 541-543.
[5]	P. Lei, “Master the Key Points in Treatment of Severe Traumatic Brain Injury,” Magazine Trauma Surgery, Vol. 8, No. 5, 2006, pp. 385-387.
[6]	P. G. Marciano, J. Brettschneider, E. Manduchi, et al., “Neuron-Specific mRNA Complexity Responses during Hippo-Campal Apoptosis after Traumatic Brain Injury,” Journal of Neuroscience, Vol. 24, No. 12, 2004, pp. 2866-2876. doi:10.1523/JNEUROSCI.5051-03.2004
[7]	M. Hasselblatt, H. Ehrenreich and A. L. Siren, “The Brain Erythropoietinsystem and Its Potential for Therapeutic Exploitationin Brain Disease,” Journal of Neurosurgical Anesthesiology, Vol. 18, No. 2, 2006, pp. 132-138. doi:10.1097/00008506-200604000-00007
[8]	H.-T. Lan and Q. J. Zhang, “Recombinant Human Erythropoietin on Focal Cerebral Ischemia-Reperfusion Injury Inflammation of the Protective Effect of r-HuEPO on inflamematory injury induced by focal cerebral ischamia/reperfusion in rats,” Chinese Neurosurgery, Vol. 22, No. 1, 2006, pp. 51-54.
[9]	A. Kumral, S. Genc, E. Ozer, et al., “Erythropoietin Downregulatesbax and DP5 proapoptotic Gene Expression In Neonatalhypoxic-Ischemic Brain Injury,” Biology of the Neonate, Vol. 89, No. 3, 2006, pp. 205-210. doi:10.1159/000089951
[10]	W. J. van Houdt, Y. S. Haviv, B. Lu, et al., “The Human Survivinpromoter: A Novel Transcriptional Targeting Strategy Fortreatment of Glioma,” Journal of Neurosurgery, Vol. 104, No. 4, 2006, pp. 583-592. doi:10.3171/jns.2006.104.4.583
[11]	P. Sompol, Y. Xu, W. Ittarat, et al., “NF-κB-Associated Mn-SOD Induction Protects against β-Amyloid-Induced Neuronal Apoptosis,” Journal of Molecular Neuroscience, Vol. 29, No. 3, 2006, pp. 279-288. doi:10.1385/JMN:29:3:279
[12]	A. J. Williams, J. R. Dave and F. C. Tortella, “Neuroprotection with the Proteasome Inhibitor MLN519 in Focal Ischemic Brain Injury: Relation to Nuclear Factor κB (NF-κB), Inflammatory Gene Expression, and Leukocyte Infiltration,” Neurochemistry International, Vol. 49, No. 2, 2006, pp. 106-112. doi:10.1016/j.neuint.2006.03.018
[13]	National Kidney Foundation—Dialysis Outcomes Quality Initiative, “NKF-DOQI Clinical Practice Guidelines for the Treatment of Anemia of Chronic Renal Failure,” American Journal of Kidney Diseases, Vol. 30, Suppl. 3, 1997, pp. S192-S240.
[14]	A.-L. Siren, et al., “Erythropoietin Prevents Neuronal Apoptosis after Cerebral Ischemia and Metabolic Stress,” Proceedings of the National Academy of Sciences, Vol. 98, No. 7, 2001, pp. 4044-4049. doi:10.1073/pnas.051606598
[15]	P. Lei, et al., “Protective Role of Erythropoietin for Traumatic Brain Injury with Shock in Rats,” Chinese Journal of Neurosurgery, Vol. 24, No. 7, 2008, pp. 553-555.