REFERENCES
1. Bracken MB, Freeman DH, Hellenbrand K. Incidence of acute traumatic spinal cord injury in the United States, 1970-1977. Am J Epidemiol 1981;113:615-22.
2. Garfin SR, Shackford SR, Marshall LF, Drummond JC. Care of the multiply injured patient with cervical spine injury. Clin Orthop 1989;239:19-29.
3. Green BA, Klose JK, Goldberg ML. Clinical and research considerations in spinal cord injury. In: Becker DP, editor. Central nervous system trauma status report Washington, DC: National Institutes of Health; 1985. pp. 341-68.
4. Green BA, Magana I. Spinal injury pain. In: Long DM, editor. Current therapy in neurological surgery Philadelphia: BC Decker; 1989. pp. 294-7.
5. Woodruff BA, Baron RCA. Description of nonfatal spinal cord injury using a hospital-based registry. Am J Prev Med 1994;10:10-4.
6. Young JS, Northrup NE. Statistical information pertaining to some of the most commonly asked questions about spinal cord injury. Spinal Cord Injury Digest 1979;1:11.
7. Green BA, Eismont FJ, O’Heir JT. Pre-hospital management of spinal cord injuries. Paraplegia 1987;25:229-38.
8. Ray SK, Hogan EL, Banik NL. Calpain in the pathophysiology of spinal cord injury: Neuroprotection with calpain inhibitors. Brain Res Rev 2003;42:169-85.
9. Rossignol S, Schwab M, Schwartz M, Fehlings G. Spinal cord injury: time to move? J Neurosci 2007;27:11782-92.
10. Huang H, Liu H, Yan R, Hu M. PI3K/Akt and ERK/MAPK signaling promote different aspects of neuron survival and axonal regrowth following, rat facial nerve axotomy. Neurochem Res 2017;42:3515-24.
11. Xu B, Chen S, Luo Y, Chen Z, Liu L, et al. Calcium signaling is involved in cadmium-induced neuronal apoptosis via induction of reactive oxygen species and activation of MAPK/mTOR network. PLoS One 2011;6:e19052.
12. McAndrew CW, Gastwirt RF, Donoghue DJ. The atypical CDK activator Spy1 regulates the intrinsic DNA damage response and is dependent upon p53 to inhibit apoptosis. Cell Cycle 2009;8:66-75.
13. Yıldız Ünal A, Korulu Ş, Karabay A. SpeedyRINGO inhibits calpain-directed apoptosis in neurons. J Alzheimers Dis 2012;31:779-91.
14. Wang XD, Zhu MW, Shan D, Wang SY, Yin X, et al. Spy1, a unique cell cycle regulator, alters viability in ALS motor neurons and cell lines in response to mutant SOD1-induced DNA damage. DNA Repair (Amst) 2019;74:51-62.
15. Huang Y, Liu Y, Chen Y, Yu X, Yang J, et al. Peripheral nerve lesion induces an up-regulation of Spy1 in rat spinal cord. Cell Mol Neurobiol 2009;29:403-11.
16. Golipour A, Myers D, Seagroves T, Murphy D, Evan GI, et al. The Spy1/RINGO family represents a novel mechanism regulating mammary growth and tumorigenesis. Cancer Res 2008;68:3591-600.
17. Liu ML, Cheng YM, Jia MC. LM23 is essential for spermatogenesis in Rattus norvegicus. Front Biosci 2010;2:187-94.
18. Liu P, Begley M, Michowski W, Inuzuka H, Ginzberg M, et al. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature 2014;508:541-5.
19. Platt SR. The role of glutamate in central nervous system health and disease-a review. Vet J 2007;173:278-86.
20. Gagliardi RJ. Neuroprotection, excitotoxicity and NMDA antagonists. Arq Neuropsiquiatr 2000;58:583-8.
21. Berliocchi L, Bano D, Nicotera P. Ca2+ signals and death programmes in neurons. Philos Trans R Soc Lond B Biol Sci 2005;360:2255-8.
22. Wong PC, Cai H, Borchelt DR, Price DL. Genetically engineered mouse models of neurodegenerative diseases. Nat Neurosci 2002;5:633-9.
23. Anderson CNG, Tolkovsky AM. Role for MAPK/ERK in sympathetic neuron survival: protection against a p53-Dependent, JNK-Independent Induction of Apoptosis by Cytosine Arabinoside. J Neurosci 1999;19:664-73.
24. Institute of Medicine. Spinal cord injury: progress, promise, and priorities Washington, DC: The National Academies Press; 2005.
25. Choi DW. Methods for antagonizing glutamate neurotoxicity. Cerebrovasc Brain Metab Rev 1990;2:105-14732.
26. Du S, Rubin A, Klepper S, Barrett C, Kim YC, et al. Calcium influx and activation of Calpain I mediate acute reactive gliosis in injured spinal cord. Exp Neurol 1999;157:96-105.
27. Beirowski B, Adalbert R, Wagner D, Grumme DS, Addicks K, et al. The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves. BMC Neurosci 2005;6:6.
28. Emery E, Aldana P, Bunge MB, Puckett W, Srinivasan A, et al. Apoptosis after traumatic human spinal cord injury. J Neurosurg 1998;89:911-20.
29. Mizuno Y, Mochizuki H, Sugita Y, Goto K. Apoptosis in neurodegenerative disorders. Intern Med 1998;37:192-3.
30. Das A, Smith JA, Gibson C, Varma AK, Ray SK, et al. Estrogen receptor agonists and estrogen attenuate TNF-alpha-induced apoptosis in VSC4.1 motoneurons. J Endocrinol 2011;208:171-82.
31. Samantaray S, Sribnick EA, Das A, Knaryan VH, Matzelle D, et al. Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. J Pineal Res 2008;44:348-57.
32. Das A, McDowell M, Pava MJ, Smith JA, Reiter RJ, et al. The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors. J Pineal Res 2010;48:157-69.
33. Ray SK, Hogan EL, Banik NL. Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res Rev 2003;42:169-85.
34. Samantaray S, Sribnick EA, Das A, Thakore NP, Matzelle D, et al. Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats. Ann N Y Acad Sci 2010;1199:90-4.
36. Sribnick EA, Wingrave JM, Matzelle DD, Wilford GG, Ray SK, et al. Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats. J Neurosci Res 2005;82:283-93.
37. Wingrave JM, Schaecher KE, Sribnick EA, Wilford GG, Ray SK, et al. Early induction of secondary injury factors causing activation of calpain and mitochondria-mediated neuronal apoptosis following spinal cord injury in rats. J Neurosci Res 2003;73:95-104.
38. Mazzone GL, Nistri A. Delayed neuroprotection by riluzole against excitotoxic damage evoked by kainate on rat organotypic spinal cord cultures. Neuroscience 2011;190:318-27.
39. Rong W, Wang J, Liu X, Jiang L, Wei F, et al. 17 beta-estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int J Neurosci 2012;122:381-7.
40. Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta 2012;1822:675-84.
41. Robert AA, Zamzami M, Sam AE, Al Jadid M, Al Mubarak S. The efficacy of antioxidants in functional recovery of spinal cord injured rats: an experimental study. Neurol Sci 2012;33:785-91.
42. Bo W, Ren XJ. Control of demyelination for recovery of spinal cord injury. Chin J Traumatol 2008;11:306-10.
43. Borisoff JF, Chan CC, Hiebert GW, Oschipok L, Robertson GS, et al. Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Mol Cell Neurosci 2003;22:405-16.
44. Ferrari G, Fabris M, Gorio A. Gangliosides enhance neurite outgrowth in PC12 cells. Brain Res 1983;284:215-21.
45. Gonzenbach RR, Schwab ME. Disinhibition of neurite growth to repair the injured adult CNS: focusing on Nogo. Cell Mol Life Sci 2008;65:161-76.
46. Gorio A, Ferrari G, Fusco M, Janigro D, Zanoni R, et al. Gangliosides and their effects on rearranging peripheral and central neural pathways. Cent Nerv Syst Trauma 1984;1:29-37.
47. Liu BP, Cafferty WB, Budel SO, Strittmatter SM. Extracellular regulators of axonal growth in the adult central nervous system. Philos Trans R Soc Lond B Biol Sci 2006;361:1593-610.
50. Karimi-Abdolrezaee S, Billakanti R. Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects. Mol Neurobiol 2012;46:251-64.
51. Dergham P, Ellezam B, Essagian C, Avedissian H, Lubell WD, et al. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002;22:6570-7.
52. Dubreuil CI, Winton MJ, McKerracher L. Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J Cell Biol 2003;162:233-43.
53. Jalink K, van Corven EJ, Hengeveld T, Morii N, Narumiya S, et al. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho. J Cell Biol 1994;126:801-10.
54. Lord-Fontaine S, Yang F, Diep Q, Dergham P, Munzer S, et al. Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury. J Neurotrauma 2008;25:1309-22.
55. Sung JK, Miao L, Calvert JW, Huang L, Louis Harkey H, et al. A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat. Brain Res 2003;959:29-38.
56. Gu YL, Yin LW, Zhang Z, Liu J, Liu SJ, et al. Neurotrophin expressions in neural stem cells grafted acutely to transected spinal cord of adult rats linked to functional improvement. Cell Mol Neurobiol 2012;32:1089-97.
57. Quertainmont R, Cantinieaux D, Botman O, Sid S, Schoenen J, et al. Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and proangiogenic actions. PLoS One 2012;7:e39500.
58. Uchida K, Nakajima H, Hirai T, Yayama T, Chen K, et al. The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice. Spine 2012;37:2125-35.
59. Donnelly EM, Lamanna J, Boulis NM. Stem cell therapy for the spinal cord. Stem Cell Res Ther 2012;3:24.
60. Wang H, Fang H, Dai J, Liu G, Xu ZJ. Induced pluripotent stem cells for spinal cord injury therapy: current status and perspective. Neurol Sci 2013;34:11-7.
61. Beattie MS. Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 2004;10:580-3.
62. Okada S, Nakamura M, Renault-Mihara F, Mukaino M, Saiwai H, et al. The role of cytokine signaling in pathophysiology for spinal cord injury. Inflamm Regen 2008;28:440-6.
63. Ito M, Natsume A, Takeuchi H, Shimato S, Ohno M, et al. Type I interferon inhibits astrocytic gliosis and promotes functional recovery after spinal cordinjury by deactivation of the MEK/ERK pathway. J Neurotrauma 2009;26:41-53.
64. Askvig JM, Watt JA. The MAPK and PI3K pathways mediate CNTF-induced neuronal survival and process outgrowth in hypothalamic organotypic cultures. J Cell Commun Signal 2015;9:217-31.
65. Ray SK, Samantaray S, Smith JA, Matzelle DD, Das A, et al. Inhibition of cysteine proteases in acute and chronic spinal cord injury. Neurotherapeutics 2011;8:180-6.
66. Samantaray S, Smith JA, Das A, Matzelle DD, Varma AK, et al. Low dose estrogen prevents neuronal degeneration and microglial reactivity in an acute model of spinal cord injury: effect of dosing, route of administration, and therapy delay. Neurochem Res 2011;36:1809-16.
67. Lee JY, Choi SY, Oh TH, Yune TY. 17 beta-estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting rhoA-JNK3 activation after spinal cord injury. Endocrinology 2012;153:3815-27.
68. Bonnefont-Rousselot D, Collin F, Jore D, Gardes-Albert M. Reaction mechanism of melatonin oxidation by reactive oxygen species in vitro. J Pineal Res 2011;50:328-35.
69. Wu UI, Mai FD, Sheu JN, Chen LY, Liu YT, et al. Melatonin inhibits microglial activation, reduces pro-inflammatory cytokine levels, and rescues hippocampal neurons of adult rats with acute Klebsiella pneumoniae meningitis. J Pineal Res 2011;50:159-70.
70. Das A, Wallace G 4th, Reiter RJ, Varma AK, Ray SK, et al. Overexpression of melatonin membrane receptors increases calcium-binding proteins and protects VSC4.1 motoneurons from glutamate toxicity through multiple mechanisms. J Pineal Res 2013;54:58-68.
71. Cheng A, Gerry S, Kaldis P, Solomon MJ. Biochemical characterization of Cdk2-Speedy/Ringo A2. BMC Biochem 2005;6:19.
73. Bartek J, Lukas J. DNA damage checkpoints: from initiation to recovery or adaptation. Curr Opin Cell Biol 2007;19:238-45.
74. Attardi LD. The role of p53-mediated apoptosis as a crucial anti-tumor response to genomic instability: lessons from mouse models. Mutat Res 2005;569:145-57.
75. Gastwirt RF, Slavin DA, McAndrew CW, Donoghue DJ. Inhibition of apoptosis and checkpoint activation. J Biol Chem 2006;281:35425-35.
76. Dhariwala FA, Rajadhyaksha MS. An unusual member of the cdk family: cdk5. Cell Mol Neurobiol 2008;28:351-69.
77. Yip YP, Capriotti C, Drill E, Tsai LH, Yip JW. Cdk5 selectively affects the migration of different populations of neurons in the developing spinal cord. J Comp Neurol 2007;503:297-307.
78. Fu X, Choi YK, Qu D, Yu Y, Cheung NS, et al. Identification of nuclear import mechanisms for the neuronal Cdk5 activator. J Biol Chem 2006;281:39014-21.
79. Cruz JC, Tsai LH. Cdk5 deregulation in the pathogenesis of Alzheimer’s disease. Trends Mol Med 2004;10:452-8.
80. Zhang J, Krishnamurthy PV, Johnson GVW. Cdk5 phosphorylates p53 and regulates its activity. J Neurochem 2002;81:307-13.
81. Sedarous M, Keramaris E, O’Hare M, Melloni E, Slack RS, et al. Calpains mediate p53 activation and neuronal death evoked by DNA damage. J Biol Chem 2003;278:26031-8.
82. Wu GS. The functional interactions between the p53 and MAPK signaling pathways. Cancer Biol Ther 2004;3:156-61.
83. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53regulated genes. Nat Rev Mol Cell Biol 2008;9:402-12.
84. Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer 2009;9:724-37.
85. McCubrey JA, Linda S, Terrian DM, Milella M, Tafuri A, et al. Roles of the RAF/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007;1773:1263-84.
86. Sawe N, Steinberg G, Zhao H. Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke. J Neu rosci Res 2008;86:1659-69.
87. She QB, Bode AM, Ma WY, Chen NY, Dong Z. Resveratrol_induced activation of p53 and apoptosis is mediated by extracellular_signal_regulated protein kinases and p38 kinase. Cancer Res 2001;61:1604-10.
88. Duan WJ, Li QS, Xia MY, Tashiro S, Onodera S, et al. Silibinin activated p53 and induced autophagic death in human fibrosarcoma HT1080 cells via reactive oxygen species p38 and C-Jun N-terminal kinase pathways. Biol Pharm Bull 2011;34:47-53.
89. Xiao Y, Yan W, Lu L, Wang Y, Lu W, et al. p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death. Cell Cycle 2015;14:1548-58.
90. Persons DL, Yazlovitskaya EM, Pelling JC. Effect of extracellular signal-regulated kinase on p53 accumulation in response to cisplatin. J Biol Chem 2000;275:35778-85.
91. Kaji A, Zhang Y, Nomura M, Bode AM, Ma WY, et al. Pifithrin-alpha promotes p53- mediated apoptosis in JB6 cells. Mol Carcinog 2003;37:138-48.
92. Lin T, Mak NK, Yang MS. MAPK regulate p53 dependent cell death induced by benzo[a]pyrene: involvement of p53 phosphorylation and acetylation. Toxicology 2008;247:145-53.
93. Drosten M, Sum EY, Lechuga CG, Simón Carrasco L, Jacob HK, et al. Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway. Proc Nat Acad Sci U S A 2014;111:15155-60.
94. Singh S, Upadhyay AK, Ajay AK, Bhat MK. p53 regulates ERK activation in carboplatin induced apoptosis in cervical carcinoma: a novel target of p53 in apoptosis. FEBS Lett 2007;581:289-95.
95. Lee SY, Shin SJ, Kim HS. ERK1/2 activation mediated by the nutlin-3-induced mitochondrial translocation of p53. Int J Oncol 2013;42:1027-35.
96. Ongusaha PP, Kim JI, Fang L, Wong TW, Yancopoulos GD, et al. p53 induction and activation of DDR1 kinase counteract p53-mediated apoptosis and influence p53 regulation through a positive feedback loop. EMBO J 2003;22:1289-301.
97. Bermudez O, Jouandin P, Rottier J, Bourcier C, Pagès G, et al. Post-transcriptional regulation of the DUSP6/MKP3 phosphatase by MEK/ERK signaling and hypoxia. J Cell Physiol 2011;226:276-84.
98. Zhang H, Chi Y, Gao K, Zhang X, Yao J. p53 protein-mediated upregulation of MAP kinase phosphatase 3 (MKP3) contributes to the establishment of the cellular senescent phenotype through dephosphorylation of extracellular signalregulated kinase 1/2 (ERK1/2). J Biol Chem 2015;290:1129-40.
99. Franke TF, Kaplan DR, Cantley LC. PI3K: downstream AKT action blocks apoptosis. Cell 1997;88:435-7.
100. Wymann MP, Pirola L. Structure and function of phosphoinositide 3-kinases. Biochim Biophys Acta 1998;1436:127-50.
101. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev 1999;13:2905-27.
102. Sabbatini P, McCormick F. Phosphoinositide 3-OH kinase (PI3K) and PKB/Akt delay the onset of p53-mediated, transcriptionally dependent apoptosis. J Biol Chem 1999;274:24263-9.
103. Henry MK, Lynch JT, Eapen AK, Quelle FW. DNA damage-induced cell-cycle arrest of hematopoietic cells is overridden by activation of the PI-3 kinase/Akt signaling pathway. Blood 2001;98:834-41.
104. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci 1999;96:4240-5.
105. Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, et al. Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci 1999;96:2110-5.
106. Rossignol S, Schwab M, Schwartz M, Fehlings MG. Spinal cord injury: time to move? J Neurosci 2007;27:11782-92.
