<strong>A Comparative Morphological Study on Early Stage Treatment of Rat Spinal Cord Contusion with Recombinant Human Erythropoietin and Methylprednisolone</strong>

Abstract

Abstract:Objective：To comparatively study the morphological changes of the spinal cord in rats by treatment with recombinant human erythropoietin (rHuEPO) and methylprednisolone (MP) at an early stage after contusion injury.Methods：Spinal cord contusion model in rats was duplicated with a Benchmark^TMstereotaxic impactor. 30 min after the procedure, animals were administrated with 5000 UI·kg^-1·BW rHuEPO (i.p.) or 30 mg·kg^-1·BW MP (tail intravenous injection). Morphological changes were examined by using the Harris HE staining and Luxol fast blue staining methods in combination with the immunohistochemical NeuN staining and GFAP staining.Results： One and 3 days after the contusion procedure, the number of survived neurons, the residual myelination area and the reduction of astrocytes in the bilateral anterior horn of gray matter in and 3-5 mm around the the injury center were significantly higher in MP group than in rHuEPO group. However, 14 and 28 days after the contusion procedure, the cavity area of and surrounding the spinal cord injury site and the reduction of astrocytes were significantly larger in rHuEPO group than in MP group. In addition, the number of survival neurons and residual myelination area 3, 5 mm surrounding the injury site were significantly larger in rHuEPO group than in MP group (P<0.05).Conclusion：MP (30 mg·kg^-1·BW)treatment at the early stage after contusion damage (the first week) significantly improves the neuronal survival, reduces loss of the myelin sheath and inhibits the proliferation of astrocytes in rats with spinal cord injury. However, at a later stage (2-4 weeks after the injury) the effect of rHuEPO treatment was more significant.

Key words:traumatic spinal cord injury,recombinant human erythropoietin（rHuEPO）,methylprednisolone（MP）,Luxol fast blue,neuronal nuclei（NeuN）,glial fibrillary acidic protein（GFAP）,immuohistochemistry

CLC Number:

R965.1

GU Bing, WANG Shuo-yu, LI Hua-nan, WANG Jun, ZHANG Shui-yin.A Comparative Morphological Study on Early Stage Treatment of Rat Spinal Cord Contusion with Recombinant Human Erythropoietin and Methylprednisolone[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(6): 7-16.

References

[1] Darryl C. Baptiste, Michael G. Fehlings. Pharmacological approaches to repair the injured spinal cord [J]. J Neurotrauma, 2006, 23(3-4): 318-334.

[2] José E. Pereiraa, Luís M. Costaa, António M. Cabrita, et al. Methylprednisolone fails to improve functional and histological outcome following spinal cord injury in rats [J]. Exp Neurol, 2009, 220(1): 71-81.

[3] A. Mofidi, A. Bader, S. Pavlica. The use of erythropoietin and its derivatives to treat spinal cord injury [J]. Mini Rev Med Chem, 2011, 11(9): 763-770.

[4] 顾兵，王俊，李华南，等. 大剂量甲强龙冲击治疗大鼠脊髓挫伤的形态学研究[J]. 中国药理学通报, 2012, 28(10): 1417-1423.

[5] Young-tae Kim, Jon-Michael Caldwell, Ravi V. Bellamkonda. Nanoparticle-mediated local delivery of methylprednisolone after spinal cord injury [J]. Biomaterials, 2009, 30(13): 2582-2590.

[6] Alfredo Gorio, Necati Gokmen, Serhat Erbayraktar, et al. Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma[J]. Proc Natl Acad Sci USA, 2002, 99(14): 9450-9455.

[7] Murat Celik, Necati Gökmen, Serhat Erbayraktar, et al. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury[J]. Proc Natl Acad Sci USA, 2002, 99(4): 2258-2263.

[8] Raad Nashmi, Owen T. Jones, Michael G. Fehlings. Abnormal axonal physiology is associated with altered expression and distribution of Kv1.1 and Kv1.2 K+ channels after chronic spinal cord injury [J]. Eur J Neurosci, 2000, 12(2): 491-506.

[9] Alberto Pinzon, Alexander Marcillo, Ada Quintana, et al. A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model [J]. Brain Res, 2008, 1243: 146-151.

[10] Holly H Nash, Rosemary C. Borke, Juanita J. Anders. Ensheathing cells and methylprednisolone promote axonal regeneration and functional recovery in the lesioned adult rat spinal cord [J]. J Neurosci, 2002, 22(16): 7111-7120.

[11] Costanza Savino, Rosetta Pedotti, Fulvio Baggi, et al. Delayed administration of erythropoietin and its non-erythropoietic derivatives ameliorates chronic murine autoimmune encephalomyelitis [J]. J Neuroimmunol, 2006, 172(1-2): 27-37.

[12] Chang Chia-Mao, Lee Ming-Hsueh, Wang Ting-Chung, et al. Brain protection by methylprednisolone in rats with spinal cord injury [J]. Neuroreport, 2009, 20(10): 968-972.

[13] Abdurrahman Cetin, Kemal Nas, Hüseyin Büyükbayram, et al. The effects of systemically administered methylprednisolone and recombinant human erythropoietin after acute spinal cord compressive injury in rats[J]. Eur Spine J, 2006, 15(10): 1539-1544.

[14] Jin-Moo Lee, Ping Yan, Qingli Xiao, et al. Methylprednisolone protects oligodendrocytes but not neurons after spinal cord injury [J]. J Neurosci, 2008, 28(12): 3141-3149.

[15] Kenneth Maiese, Zhao Zhong-chong, Hou Jin-ling, et al. New strategies for Alzheimer's disease and cognitive impairment [J]. Oxid Med Cell Longev, 2009, 2(5): 279-289.

[16] Henrich Cheng, Jey-Pei Wu, Shun-Fen Tzeng. Neuroprotection of glial cell line-derived neurotrophic factor in damaged spinal cords following contusive injury [J]. J Neurosci Res, 2002, 69(3): 397-405.

[17] 刘曾旭，王向东，余庆，等. 微囊化兔嗅球细胞悬液移植对脊髓损伤大鼠GFAP及NF200表达的影响[J]. 中国临床解剖学杂志, 2009, 27(5): 566-569.

[18] 郝彦明，王洪震，徐又佳，等. 促红细胞生成素对星形胶质细胞损伤的保护作用[J]. 山东医药, 2009, 49(30): 4-6.

[19] Park Sung-Jin, Oh In-Soo, Kwon Jae-Young, et al. The effect of irradiation and methylprednisolone in spinal cord injured rats [J]. Spine, 2011, 36(6): 434-440.

[20] Liu Wei-Lin, Yi-Hsuan Lee, Shih-Ying Tsai, et al. Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes [J]. Glia, 2008, 56(13): 1390-1400.

A Comparative Morphological Study on Early Stage Treatment of Rat Spinal Cord Contusion with Recombinant Human Erythropoietin and Methylprednisolone

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