Recent advances in the pharmacologic treatment of spinal cord injury

Metabolic Brain Disease

Volumn 30, Issue 2, 2015, Pages 473-482

  Cox, April ^a   Varma, Abhay ^a   Banik, Naren ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Estrogen; Inflammation; Myelin; Neurodegeneration; Regeneration; Spinal cord injury

Indexed keywords

NEUROPROTECTIVE AGENT;

ANIMAL; HUMAN; INFLAMMATION; NERVE DEGENERATION; PATHOLOGY; SPINAL CORD INJURIES;

ANIMALS; HUMANS; INFLAMMATION; NERVE DEGENERATION; NEUROPROTECTIVE AGENTS; SPINAL CORD INJURIES;

EID: 84939876789     PISSN: 08857490     EISSN: 15737365     Source Type: Journal    
DOI: 10.1007/s11011-014-9547-y     Document Type: Article

References (96)

1. Abdanipour A, Schluesener HJ, Tiraihi T (2012) Effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science. Iran Biomed J 16(2):90–100
2. Ahmed Z, Bansal D, Tizzard K, Surey S, Esmaeili M, Douglas MR, Gonzalez AM, Berry M, Logan A (2013) Decorin blocks scarring and cystic cavitation in acute and induces scar dissolution in chronic spinal cord wounds. Neurobiol Dis. doi:10.1016/j.nbd.2013.12.008
3. Akdemir O, Ucankale M, Karaoglan A, Barut S, Sagmanligil A, Bilguvar K, Cirakoglu B, Sahan E, Colak A (2008) Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury. J Clin Neurosci: Off J Neurosurg Soc Australa 15(10):1130–1136. doi:10.1016/j.jocn.2007.08.011
4. Anthes DL, Theriault E, Tator CH (1995) Characterization of axonal ultrastructural pathology following experimental spinal cord compression injury. Brain Res 702(1–2):1–16
5. Arataki S, Tomizawa K, Moriwaki A, Nishida K, Matsushita M, Ozaki T, Kunisada T, Yoshida A, Inoue H, Matsui H (2005) Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats. J Neurotrauma 22(3):398–406. doi:10.1089/neu.2005.22.398
6. Banik NL, Powers JM, Hogan EL (1980) The effects of spinal cord trauma on myelin. J Neuropathol Exp Neurol 39(3):232–244
7. Banik NL, Hogan EL, Powers JM, Whetstine LJ (1982) Degradation of cytoskeletal proteins in experimental spinal cord injury. Neurochem Res 7(12):1465–1475
8. Bell MT, Puskas F, Agoston VA, Cleveland JC Jr, Freeman KA, Gamboni F, Herson PS, Meng X, Smith PD, Weyant MJ, Fullerton DA, Reece TB (2013) Toll-like receptor 4-dependent microglial activation mediates spinal cord ischemia-reperfusion injury. Circulation 128(11 Suppl 1):S152–S156. doi:10.1161/CIRCULATIONAHA.112.000024
9. Bracken MB (1992) Pharmacological treatment of acute spinal cord injury: current status and future prospects. Paraplegia 30(2):102–107. doi:10.1038/sc.1992.34
10. Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, Silten RM, Hellenbrand KG, Ransohoff J, Hunt WE, Perot PL Jr et al (1984) Efficacy of methylprednisolone in acute spinal cord injury. JAMA: J Am Med Assoc 251(1):45–52
11. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J et al (1990) A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322(20):1405–1411. doi:10.1056/NEJM199005173222001
12. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W (1997) Administration of methylprednisolone for 24 or 48 h or tirilazad mesylate for 48 h in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA: J Am Med Assoc 277(20):1597–1604
13. Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR (2005) Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 202(1):145–156. doi:10.1084/jem.20041918
14. Brambilla R, Hurtado A, Persaud T, Esham K, Pearse DD, Oudega M, Bethea JR (2009) Transgenic inhibition of astroglial NF-kappa B leads to increased axonal sparing and sprouting following spinal cord injury. J Neurochem 110(2):765–778. doi:10.1111/j.1471-4159.2009.06190.x
15. Brosamle C, Huber AB, Fiedler M, Skerra A, Schwab ME (2000) Regeneration of lesioned corticospinal tract fibers in the adult rat induced by a recombinant, humanized IN-1 antibody fragment. J Neurosci: Off J Soc Neurosci 20(21):8061–8068
16. Busch SA, Hamilton JA, Horn KP, Cuascut FX, Cutrone R, Lehman N, Deans RJ, Ting AE, Mays RW, Silver J (2011) Multipotent adult progenitor cells prevent macrophage-mediated axonal dieback and promote regrowth after spinal cord injury. J Neurosci: Off J Soc Neurosci 31(3):944–953. doi:10.1523/JNEUROSCI.3566-10.2011
17. Byrnes KR, Stoica BA, Fricke S, Di Giovanni S, Faden AI (2007) Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury. Brain: J Neurol 130(Pt 11):2977–2992. doi:10.1093/brain/awm179
18. Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ (2012) Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain: J Neurol 135(Pt 4):1224–1236. doi:10.1093/brain/aws072
19. Chatzipanteli K, Yanagawa Y, Marcillo AE, Kraydieh S, Yezierski RP, Dietrich WD (2000) Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J Neurotrauma 17(4):321–332
20. Chen SH, Yeh CH, Lin MY, Kang CY, Chu CC, Chang FM, Wang JJ (2010) Premarin improves outcomes of spinal cord injury in male rats through stimulating both angiogenesis and neurogenesis. Crit Care Med 38(10):2043–2051. doi:10.1097/CCM.0b013e3181ef44dc
21. Cho DC, Cheong JH, Yang MS, Hwang SJ, Kim JM, Kim CH (2011) The effect of minocycline on motor neuron recovery and neuropathic pain in a rat model of spinal cord injury. J Korean Neurosurg Soc 49(2):83–91. doi:10.3340/jkns.2011.49.2.83
22. David S, Kroner A (2011) Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 12(7):388–399. doi:10.1038/nrn3053
23. De Nicola AF, Gonzalez SL, Labombarda F, Deniselle MC, Garay L, Guennoun R, Schumacher M (2006) Progesterone treatment of spinal cord injury: effects on receptors, neurotrophins, and myelination. J Molec Neurosci MN 28(1):3–15. doi:10.1385/JMN:30:3:341
24. Dididze M, Green BA, Dalton Dietrich W, Vanni S, Wang MY, Levi AD (2013) Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Spinal Cord 51(5):395–400. doi:10.1038/sc.2012.161
25. Doble A (1999) The role of excitotoxicity in neurodegenerative disease: implications for therapy. Pharmacol Ther 81(3):163–221
26. Donovan WH (2007) Donald Munro Lecture. Spinal cord injury–past, present, and future. J Spinal Cord Med 30(2):85–100
27. Ducker TB, Hamit HF (1969) Experimental treatments of acute spinal cord injury. J Neurosurg 30(6):693–697. doi:10.3171/jns.1969.30.6.0693
28. Esposito E, Genovese T, Caminiti R, Bramanti P, Meli R, Cuzzocrea S (2009) Melatonin reduces stress-activated/mitogen-activated protein kinases in spinal cord injury. J Pineal Res 46(1):79–86. doi:10.1111/j.1600-079X.2008.00633.x
29. Esposito E, Paterniti I, Mazzon E, Genovese T, Galuppo M, Meli R, Bramanti P, Cuzzocrea S (2011) MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma. BMC Neurosci 12:31. doi:10.1186/1471-2202-12-31
30. Fehlings MG, Theodore N, Harrop J, Maurais G, Kuntz C, Shaffrey CI, Kwon BK, Chapman J, Yee A, Tighe A, McKerracher L (2011) A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma 28(5):787–796. doi:10.1089/neu.2011.1765
31. Fleming JC, Norenberg MD, Ramsay DA, Dekaban GA, Marcillo AE, Saenz AD, Pasquale-Styles M, Dietrich WD, Weaver LC (2006) The cellular inflammatory response in human spinal cords after injury. Brain: J Neurol 129(Pt 12):3249–3269. doi:10.1093/brain/awl296
32. Fujimoto T, Nakamura T, Ikeda T, Takagi K (2000) Potent protective effects of melatonin on experimental spinal cord injury. Spine 25(7):769–775
33. Geisler FH, Dorsey FC, Coleman WP (1991) Recovery of motor function after spinal-cord injury—a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med 324(26):1829–1838. doi:10.1056/NEJM199106273242601
34. Geisler FH, Coleman WP, Grieco G, Poonian D (2001) The Sygen multicenter acute spinal cord injury study. Spine 26(24 Suppl):S87–S98
35. Green DR (1998) Apoptotic pathways: the roads to ruin. Cell 94(6):695–698
36. Gris D, Marsh DR, Oatway MA, Chen Y, Hamilton EF, Dekaban GA, Weaver LC (2004) Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci: Off J Soc Neurosci 24(16):4043–4051. doi:10.1523/JNEUROSCI.5343-03.2004
37. Grossman RG, Fehlings MG, Frankowski RF, Burau KD, Chow DS, Tator C, Teng A, Toups EG, Harrop JS, Aarabi B, Shaffrey CI, Johnson MM, Harkema SJ, Boakye M, Guest JD, Wilson JR (2013) A prospective, multicenter, phase i matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma. doi:10.1089/neu.2013.2969
38. Gwak YS, Kang J, Unabia GC, Hulsebosch CE (2012) Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp Neurol 234(2):362–372. doi:10.1016/j.expneurol.2011.10.010
39. Hawryluk GW, Rowland J, Kwon BK, Fehlings MG (2008) Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury. Neurosurg Focus 25(5):E14. doi:10.3171/foc.2008.25.11.e14
40. Hunt D, Coffin RS, Anderson PN (2002) The Nogo receptor, its ligands and axonal regeneration in the spinal cord; a review. J Neurocytol 31(2):93–120
41. Joint Section on Disorders of the Spine and Peripheral Nerves of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (2013) Guideline for the management of acute cervical and spinal cord injuries. Neurosurgery 72 (supplement 2):1–259. http://neurosurgerycns.wordpress.com/2013/02/20/guidelines-for-the-management-of-acute-cervical-spine-and-spinal-cord-injury/. 2013
42. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG (2009) Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci: Off J Soc Neurosci 29(43):13435–13444. doi:10.1523/JNEUROSCI.3257-09.2009
43. Kwon BK, Sekhon LH, Fehlings MG (2010) Emerging repair, regeneration, and translational research advances for spinal cord injury. Spine 35(21 Suppl):S263–S270. doi:10.1097/BRS.0b013e3181f3286d
44. Labombarda F, Gonzalez S, Lima A, Roig P, Guennoun R, Schumacher M, De Nicola AF (2011) Progesterone attenuates astro- and microgliosis and enhances oligodendrocyte differentiation following spinal cord injury. Exp Neurol 231(1):135–146. doi:10.1016/j.expneurol.2011.06.001
45. Lee JK, Geoffroy CG, Chan AF, Tolentino KE, Crawford MJ, Leal MA, Kang B, Zheng B (2010) Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 66(5):663–670. doi:10.1016/j.neuron.2010.05.002
46. Lee JY, Choi SY, Oh TH, Yune TY (2012) 17beta-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. Endocrinology 153(8):3815–3827. doi:10.1210/en.2012-1068
47. Levi AD, Casella G, Green BA, Dietrich WD, Vanni S, Jagid J, Wang MY (2010) Clinical outcomes using modest intravascular hypothermia after acute cervical spinal cord injury. Neurosurgery 66(4):670–677. doi:10.1227/01.NEU.0000367557.77973.5F
48. Lin CY, Strom A, Vega VB, Kong SL, Yeo AL, Thomsen JS, Chan WC, Doray B, Bangarusamy DK, Ramasamy A, Vergara LA, Tang S, Chong A, Bajic VB, Miller LD, Gustafsson JA, Liu ET (2004) Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells. Genome Biol 5(9):R66. doi:10.1186/gb-2004-5-9-r66
49. Liu D, Thangnipon W, McAdoo DJ (1991) Excitatory amino acids rise to toxic levels upon impact injury to the rat spinal cord. Brain Res 547(2):344–348
50. Liu NK, Zhang YP, Titsworth WL, Jiang X, Han S, Lu PH, Shields CB, Xu XM (2006) A novel role of phospholipase A2 in mediating spinal cord secondary injury. Ann Neurol 59(4):606–619. doi:10.1002/ana.20798
51. Lu WH, Wang CY, Chen PS, Wang JW, Chuang DM, Yang CS, Tzeng SF (2013) Valproic acid attenuates microgliosis in injured spinal cord and purinergic P2X4 receptor expression in activated microglia. J Neurosci Res 91(5):694–705. doi:10.1002/jnr.23200
52. Ma M, Ferguson TA, Schoch KM, Li J, Qian Y, Shofer FS, Saatman KE, Neumar RW (2013) Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration. Neurobiol Dis 56:34–46. doi:10.1016/j.nbd.2013.03.009
53. Mahon RT, Auker CR, Bradley SG, Mendelson A, Hall AA (2013) The emulsified perfluorocarbon Oxycyte improves spinal cord injury in a swine model of decompression sickness. Spinal Cord 51(3):188–192. doi:10.1038/sc.2012.135
54. McDowell ML, Das A, Smith JA, Varma AK, Ray SK, Banik NL (2011) Neuroprotective effects of genistein in VSC4.1 motoneurons exposed to activated microglial cytokines. Neurochem Int 59(2):175–184. doi:10.1016/j.neuint.2011.04.011
55. Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL (2013) Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur J Pharmacol 698(1–3):6–18. doi:10.1016/j.ejphar.2012.10.032
56. Momeni HR, Kanje M (2006) Calpain inhibitors delay injury-induced apoptosis in adult mouse spinal cord motor neurons. Neuroreport 17(8):761–765. doi:10.1097/01.wnr.0000220127.01597.04
57. Muradov JM, Hagg T (2013) Intravenous infusion of magnesium chloride improves epicenter blood flow during the acute stage of contusive spinal cord injury in rats. J Neurotrauma 30(10):840–852. doi:10.1089/neu.2012.2670
58. Muradov JM, Ewan EE, Hagg T (2013) Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats. Exp Neurol 249:59–73. doi:10.1016/j.expneurol.2013.08.009
59. Ok JH, Kim YH, Ha KY (2012) Neuroprotective effects of hypothermia after spinal cord injury in rats: comparative study between epidural hypothermia and systemic hypothermia. Spine 37(25):E1551–E1559. doi:10.1097/BRS.0b013e31826ff7f1
60. Olsen ML, Campbell SC, McFerrin MB, Floyd CL, Sontheimer H (2010) Spinal cord injury causes a wide-spread, persistent loss of Kir4.1 and glutamate transporter 1: benefit of 17 beta-oestradiol treatment. Brain: J Neurol 133(Pt 4):1013–1025. doi:10.1093/brain/awq049
61. Park SW, Yi JH, Miranpuri G, Satriotomo I, Bowen K, Resnick DK, Vemuganti R (2007) Thiazolidinedione class of peroxisome proliferator-activated receptor gamma agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats. J Pharmacol Exp Ther 320(3):1002–1012. doi:10.1124/jpet.106.113472
62. Park K, Lee Y, Park S, Lee S, Hong Y, Kil Lee S (2010) Synergistic effect of melatonin on exercise-induced neuronal reconstruction and functional recovery in a spinal cord injury animal model. J Pineal Res 48(3):270–281. doi:10.1111/j.1600-079X.2010.00751.x
63. Park S, Lee SK, Park K, Lee Y, Hong Y, Lee S, Jeon JC, Kim JH, Lee SR, Chang KT (2012) Beneficial effects of endogenous and exogenous melatonin on neural reconstruction and functional recovery in an animal model of spinal cord injury. J Pineal Res 52(1):107–119. doi:10.1111/j.1600-079X.2011.00925.x
64. Ray SK, Wilford GG, Matzelle DC, Hogan EL, Banik NL (1999) Calpeptin and methylprednisolone inhibit apoptosis in rat spinal cord injury. Ann N Y Acad Sci 890:261–269
65. Ray SK, Matzelle DD, Wilford GG, Hogan EL, Banik NL (2001) Cell death in spinal cord injury (SCI) requires de novo protein synthesis. Calpain inhibitor E-64-d provides neuroprotection in SCI lesion and penumbra. Ann N Y Acad Sci 939:436–449
66. Ray SK, Hogan EL, Banik NL (2003) Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res Brain Res Rev 42(2):169–185
67. Ren Y, Young W (2013) Managing Inflammation after spinal cord injury through manipulation of macrophage function. Neural Plast 2013:945034. doi:10.1155/2013/945034
68. Samantaray S, Sribnick EA, Das A, Knaryan VH, Matzelle DD, Yallapragada AV, Reiter RJ, Ray SK, Banik NL (2008) Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. J Pineal Res 44(4):348–357. doi:10.1111/j.1600-079X.2007.00534.x
69. Samantaray S, Das A, Thakore NP, Matzelle DD, Reiter RJ, Ray SK, Banik NL (2009) Therapeutic potential of melatonin in traumatic central nervous system injury. J Pineal Res 47(2):134–142. doi:10.1111/j.1600-079X.2009.00703.x
70. Samantaray S, Smith JA, Das A, Matzelle DD, Varma AK, Ray SK, Banik NL (2011) 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 36(10):1809–1816. doi:10.1007/s11064-011-0498-y
71. Schiaveto-de-Souza A, da Silva CA, Defino HL, Del Bel EA (2013) Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord. Braz J Med Biol Res Rev Bras Pesquisas Med Biol/Soc Bras Biofis [et al] 46(4):348–358
72. Schnell L, Schwab ME (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343(6255):269–272. doi:10.1038/343269a0
73. Schomberg D, Olson JK (2012) Immune responses of microglia in the spinal cord: contribution to pain states. Exp Neurol 234(2):262–270. doi:10.1016/j.expneurol.2011.12.021
74. Schroeder JL, Highsmith JM, Young HF, Mathern BE (2008) Reduction of hypoxia by perfluorocarbon emulsion in a traumatic spinal cord injury model. J Neurosurg Spine 9(2):213–220. doi:10.3171/spi/2008/9/8/213
75. Schwab ME, Kapfhammer JP, Bandtlow CE (1993) Inhibitors of neurite growth. Annu Rev Neurosci 16:565–595. doi:10.1146/annurev.ne.16.030193.003025
76. Schwartz G, Fehlings MG (2001) Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole. J Neurosurg 94(2 Suppl):245–256
77. Siriphorn A, Dunham KA, Chompoopong S, Floyd CL (2012) Postinjury administration of 17beta-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats. J Comp Neurol 520(12):2630–2646. doi:10.1002/cne.23056
78. Sonmez E, Kabatas S, Ozen O, Karabay G, Turkoglu S, Ogus E, Yilmaz C, Caner H, Altinors N (2013) Minocycline treatment inhibits lipid peroxidation, preserves spinal cord ultrastructure, and improves functional outcome after traumatic spinal cord injury in the rat. Spine 38(15):1253–1259. doi:10.1097/BRS.0b013e3182895587
79. Springer JE, Azbill RD, Kennedy SE, George J, Geddes JW (1997) Rapid calpain I activation and cytoskeletal protein degradation following traumatic spinal cord injury: attenuation with riluzole pretreatment. J Neurochem 69(4):1592–1600
80. Sribnick EA, Matzelle DD, Banik NL, Ray SK (2007) Direct evidence for calpain involvement in apoptotic death of neurons in spinal cord injury in rats and neuroprotection with calpain inhibitor. Neurochem Res 32(12):2210–2216. doi:10.1007/s11064-007-9433-7
81. Sribnick EA, Samantaray S, Das A, Smith J, Matzelle DD, Ray SK, Banik NL (2010) Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats. J Neurosci Res 88(8):1738–1750. doi:10.1002/jnr.22337
82. Stirling DP, Khodarahmi K, Liu J, McPhail LT, McBride CB, Steeves JD, Ramer MS, Tetzlaff W (2004) Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J Neurosci: Off J Soc Neurosci 24(9):2182–2190. doi:10.1523/jneurosci.5275-03.2004
83. Takeda M, Kawaguchi M, Kumatoriya T, Horiuchi T, Watanabe K, Inoue S, Konishi N, Furuya H (2011) Effects of minocycline on hind-limb motor function and gray and white matter injury after spinal cord ischemia in rats. Spine 36(23):1919–1924. doi:10.1097/BRS.0b013e3181ffda29
84. Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75(1):15–26. doi:10.3171/jns.1991.75.1.0015
85. Tator CH, Koyanagi I (1997) Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg 86(3):483–492. doi:10.3171/jns.1997.86.3.0483
86. Teng YD, Choi H, Onario RC, Zhu S, Desilets FC, Lan S, Woodard EJ, Snyder EY, Eichler ME, Friedlander RM (2004) Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury. Proc Natl Acad Sci U S A 101(9):3071–3076. doi:10.1073/pnas.0306239101
87. Thomas AJ, Nockels RP, Pan HQ, Shaffrey CI, Chopp M (1999) Progesterone is neuroprotective after acute experimental spinal cord trauma in rats. Spine 24(20):2134–2138
88. Titsworth WL, Cheng X, Ke Y, Deng L, Burckardt KA, Pendleton C, Liu NK, Shao H, Cao QL, Xu XM (2009) Differential expression of sPLA2 following spinal cord injury and a functional role for sPLA2-IIA in mediating oligodendrocyte death. Glia 57(14):1521–1537. doi:10.1002/glia.20867
89. Tsai EC, Tator CH (2005) Neuroprotection and regeneration strategies for spinal cord repair. Curr Pharm Des 11(10):1211–1222
90. Tsubokawa T, Solaroglu I, Yatsushige H, Cahill J, Yata K, Zhang JH (2006) Cathepsin and calpain inhibitor E64d attenuates matrix metalloproteinase-9 activity after focal cerebral ischemia in rats. Stroke J Cereb Circ 37(7):1888–1894. doi:10.1161/01.STR.0000227259.15506.24
91. Watanabe K, Kawaguchi M, Kitagawa K, Inoue S, Konishi N, Furuya H (2012) Evaluation of the neuroprotective effect of minocycline in a rabbit spinal cord ischemia model. J Cardiothorac Vasc Anesth 26(6):1034–1038. doi:10.1053/j.jvca.2012.05.003
92. Wells JE, Hurlbert RJ, Fehlings MG, Yong VW (2003) Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain: J Neurol 126(Pt 7):1628–1637. doi:10.1093/brain/awg178
93. Wu Y, Satkunendrarajah K, Teng Y, Chow DS, Buttigieg J, Fehlings MG (2013) Delayed post-injury administration of riluzole is neuroprotective in a preclinical rodent model of cervical spinal cord injury. J Neurotrauma 30(6):441–452. doi:10.1089/neu.2012.2622
94. Yacoub A, Hajec MC, Stanger R, Wan W, Young H, Mathern BE (2013) Neuroprotective effects of perflurocarbon (Oxycyte) after contusive spinal cord injury. J Neurotrauma. doi:10.1089/neu.2013.3037
95. York EM, Petit A, Roskams AJ (2013) Epigenetics of neural repair following spinal cord injury. Neurother: J Am Soc Exp Neuro Ther 10(4):757–770. doi:10.1007/s13311-013-0228-z
96. Yu CG, Joshi A, Geddes JW (2008) Intraspinal MDL28170 microinjection improves functional and pathological outcome following spinal cord injury. J Neurotrauma 25(7):833–840. doi:10.1089/neu.2007.0490