EXPERIMENTAL STUDY ON NEUROPROTECTIVE EFFECT OF 17β-ESTRADIOL AFTER CHRONIC SPINAL CORD INJURY IN OVARIECTOMIZED RATS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Yanhong , YANG Tongqun , WANG Bingyi , ZHANG Qian , GENG Xilin , WANG Hao.

Department of Trauma Surgery, Second Hospital of Lanzhou University, Lanzhou Gansu, 730030, P.R.China. Corresponding author: YANG Tongqun, E-mail: lyh702@126.com;

Corresponding author：

Keywords：

17β-estradiol; Chronic spinal cord injury; Nerve protection; Rat

DOI：

10.7507/1002-1892.20130159

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of 17β-estradiol on the cell apoptosis after chronic spinal cord injury in ovariectomized rats. Methods A total of 90 female Wistar rats (weighing, 220-250 g) received removal of bilateral ovaries. After 2 weeks, the rats were randomly divided into 3 groups (n=30): sham-operation group (group A); chronic gradual spinal cord injury model and 17β-estradiol treatment group (group B); and chronic gradual spinal cord injury model and normal saline treatment group (group C). Rats of group A only received removal of spinous process at T10. Rats of groups B and C were made the models of chronic gradual spinal cord injury, and then 17β-estradiol (100 μg/kg, twice a week) and normal saline were given by peritoneal injection, respectively. The cell apoptosis and positive cells of Caspase-3 were examined by the TUNEL methods and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28, and 60 days after modeling; and the neurological function was evaluated by Tarlov scale and inclined plane test scoring. Results At 14, 28, and 60 days after modeling, Tarlov scale and inclined plane test scores of group B were significantly better than those of group C (P lt; 0.05), but were significantly lower than those of group A (P lt; 0.05). At 28 days after modeling, HE staining showed that the edema of spinal gray matter and the neurons, the proliferation of glial cells and astrocytes, and less pathologic change were observed in group B; and the pathological changes in group B were mitigated than in group C. At 60 days after modeling, edema of spinal gray matter and the neurons was significantly ameliorated in group B. At 14, 28, and 60 days after modeling, the rate of Caspase-3 positive cells in group B was significantly lower than in group C (P lt; 0.05), but was significantly higher than in group A (P lt; 0.05). At 7, 14, 28, and 60 days after modeling, the cell apoptotic rate was significantly lower in group B than in group C (P lt; 0.05), but was significantly higher than in group A (P lt; 0.05). Conclusion 17β-estradiol can reduce the numbers of apoptotic cells and promote the nerve function recovery after chronic spinal cord injury of rats.

Citation： LI Yanhong,YANG Tongqun,WANG Bingyi,ZHANG Qian,GENG Xilin,WANG Hao.. EXPERIMENTAL STUDY ON NEUROPROTECTIVE EFFECT OF 17β-ESTRADIOL AFTER CHRONIC SPINAL CORD INJURY IN OVARIECTOMIZED RATS. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(6): 720-725. doi: 10.7507/1002-1892.20130159 Copy

1.	Sur P, Sribnick EA, Wingrave JM, et al. Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells. Brain Res, 2003, 971(2): 178-188.
2.	Yune TY, Kim SJ, Lee SM, et al. Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma, 2004, 21(3): 293-306.
3.	Schramm J. A model for chronic spinal cord compression in cats. Neurochirurgia (Stuttg), 1982, 25(4): 113-115.
4.	Salzman SK, Puniak MA, Liu ZJ, et al. The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma. Ann Neurol, 1991, 30(4): 533-541.
5.	Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in the rat. Neurosurg, 1977, 47(4): 577-581.
6.	Cardona-Rossinyol A, Mir M, Caraballo-Miralles V, et al. Neuroprotective effects of estradiol on motoneurons in a model of rat spinal cord embryonic explants. J Cell Mol Neurobiol, 2013, 33(3): 421-432.
7.	Das A, Smith JA, Gibson C, et al. Estrogen receptor agonists and estrogen attenuate TNF-α-induced apoptosis in VSC4.1 motoneurons. J Endocrinol, 2011, 208(2): 171-182.
8.	Sribnick EA, Wingrave JM, Matzelle DD, et al. Estrogen as a neuroprotective agent in the treatment of spinal cord injury. Ann N Y Acad Sci, 2003, 993: 125-133.
9.	Sribnik EA, Ray SK, Nawak MW, et al. 17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons. J Neurosci Res, 2004, 76(5): 688-696.
10.	Mermelstein PG. Membrane-localised oestrogen receptor alpha and beta influence neuronal activity through activation of metabotropic glutamate receptors. J Neuroendocrinol, 2009, 21(4): 257-262.
11.	Rong W, Wang J, Liu X, et al. 17β-estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int J Neurosci, 2012, 122(7): 381-387.
12.	Kachadroka S, Hall AM, Niedzielko TL, et al. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats. J Neurotrauma, 2010, 27(3): 611-626.
13.	Lee JY, Choi SY, Oh TH, et al. 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. J Endocrinology, 2012, 153(8): 3815-3827.
14.	Siriphorn A, Dunham KA, Chompoopong S, et al. Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats. J Comp Neurol, 2012, 520(12): 2630-2646.
15.	Thompson KE, Sipes IG, Greenstein BD, et al. 17beta-estradiol affords protection against 4-vinylcyclohexenediepoxide-induced ovarian follicle loss in Fischer-344 rats. Endocrinology, 2002, 143(3): 1058-1065.
16.	Khalaj L, Peirovi H, Khodagholi F, et al. Acute 17β-estradiol pretreatment protects against abdominal aortic occlusion induced spinal cord ischemic-reperfusion injury. J Neurochem Res, 2011, 36(2): 268-280.
17.	Maier JK, Lahoua Z, Gendron NH, et al. The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. J Neurosci, 2002, 22(6): 2035-2043.
18.	Emery E, Aldana P, Bunge MB, et al. Apoptosis after traumatic human spinal cord injury. J Neurosurg, 2002, 89(6): 911-920.
19.	Matsushita K, Wu Y, Qiu J, et al. Fas receptor and neuronal cell death after spinal cord ischemia. J Neurosci, 2000, 20(18): 6879-6887.
20.	Sribnick EA, Matzelle DD, Ray SK, et al. Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. J Neurosci Res, 2006, 84(5): 1064-1075.

1. Sur P, Sribnick EA, Wingrave JM, et al. Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells. Brain Res, 2003, 971(2): 178-188.
2. Yune TY, Kim SJ, Lee SM, et al. Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma, 2004, 21(3): 293-306.
3. Schramm J. A model for chronic spinal cord compression in cats. Neurochirurgia (Stuttg), 1982, 25(4): 113-115.
4. Salzman SK, Puniak MA, Liu ZJ, et al. The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma. Ann Neurol, 1991, 30(4): 533-541.
5. Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in the rat. Neurosurg, 1977, 47(4): 577-581.
6. Cardona-Rossinyol A, Mir M, Caraballo-Miralles V, et al. Neuroprotective effects of estradiol on motoneurons in a model of rat spinal cord embryonic explants. J Cell Mol Neurobiol, 2013, 33(3): 421-432.
7. Das A, Smith JA, Gibson C, et al. Estrogen receptor agonists and estrogen attenuate TNF-α-induced apoptosis in VSC4.1 motoneurons. J Endocrinol, 2011, 208(2): 171-182.
8. Sribnick EA, Wingrave JM, Matzelle DD, et al. Estrogen as a neuroprotective agent in the treatment of spinal cord injury. Ann N Y Acad Sci, 2003, 993: 125-133.
9. Sribnik EA, Ray SK, Nawak MW, et al. 17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons. J Neurosci Res, 2004, 76(5): 688-696.
10. Mermelstein PG. Membrane-localised oestrogen receptor alpha and beta influence neuronal activity through activation of metabotropic glutamate receptors. J Neuroendocrinol, 2009, 21(4): 257-262.
11. Rong W, Wang J, Liu X, et al. 17β-estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int J Neurosci, 2012, 122(7): 381-387.
12. Kachadroka S, Hall AM, Niedzielko TL, et al. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats. J Neurotrauma, 2010, 27(3): 611-626.
13. Lee JY, Choi SY, Oh TH, et al. 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. J Endocrinology, 2012, 153(8): 3815-3827.
14. Siriphorn A, Dunham KA, Chompoopong S, et al. Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats. J Comp Neurol, 2012, 520(12): 2630-2646.
15. Thompson KE, Sipes IG, Greenstein BD, et al. 17beta-estradiol affords protection against 4-vinylcyclohexenediepoxide-induced ovarian follicle loss in Fischer-344 rats. Endocrinology, 2002, 143(3): 1058-1065.
16. Khalaj L, Peirovi H, Khodagholi F, et al. Acute 17β-estradiol pretreatment protects against abdominal aortic occlusion induced spinal cord ischemic-reperfusion injury. J Neurochem Res, 2011, 36(2): 268-280.
17. Maier JK, Lahoua Z, Gendron NH, et al. The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. J Neurosci, 2002, 22(6): 2035-2043.
18. Emery E, Aldana P, Bunge MB, et al. Apoptosis after traumatic human spinal cord injury. J Neurosurg, 2002, 89(6): 911-920.
19. Matsushita K, Wu Y, Qiu J, et al. Fas receptor and neuronal cell death after spinal cord ischemia. J Neurosci, 2000, 20(18): 6879-6887.
20. Sribnick EA, Matzelle DD, Ray SK, et al. Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. J Neurosci Res, 2006, 84(5): 1064-1075.

Chinese Journal of Reparative and Reconstructive Surgery

EXPERIMENTAL STUDY ON NEUROPROTECTIVE EFFECT OF 17β-ESTRADIOL AFTER CHRONIC SPINAL CORD INJURY IN OVARIECTOMIZED RATS

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content