Pathophysiology of the spinal cord injury

Abstract

Spinal cord injury (SCI) causes significant morbidity and mortality leading to serious social problems. Although many studies conducted on it, any universal treatment protocol has not been accepted to date. Studies about treatment of SCI focused on two mechanisms. First is usage of neuroprotective agents, and second are regeneration studies to improve axonal functions of injured spinal cord. Pathophysiological changes occurring after SCI has to be well understood in order to develop ideal treatment. J Clin Exp Invest 2014; 5 (1): 131-136

Keywords

• Spinal cord injury, pathophysiology

Omurilik yaralanmaların patofizyolojisi

Öz

Omurilik yaralanması toplumsal düzeyde problemlere yol açan morbidite ve mortalitenin önemli nedenlerindendir.Günümüze kadar pek çok çalışma yapılmasına rağmen evresel tedavi protokolü geliştirilememiştir. Omurilik yaralanmalarının tedavisinde çalışmalar iki mekanizma üzerine yoğunlaşmıştır. Birincisi hasar görmüş omuriliği koruyucu nöroprotektif ajanların kullanılması diğeri hasarlanmış omurilikte aksonların fonksiyonlarını kazanabilecekleri rejenerasyon çalışmalarıdır. Etkin tedavinin bulunabilmesi için omurilik yaralanması sonrası patofizyolojik değişiklikler iyi bilinmelidir.

Anahtar Kelimeler

• Omurilik yaralanması, patofizyoloji

Kaynakça

1. Tator CH. Biology of neurological recovery and func- tional restoration after spinal cord injury. Neurosur- gery 1998;42:696-707.
2. Dumont RJ, Verma S, Okonkwo DO, et al. Acute spinal cord injury, part II: contemporary pharmacotherapy. Clin Neuropharmacol 2001;24:265-279.
3. Li M, Ona VO, Chen M, et al. Friedlander RM. Func- tional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spi- nal cord injury. Neuroscience 2000;99:333-342.
4. Dumont AS, Dumont RJ, Oskouian RJ. Will improved understanding of the pathophysiological mechanisms involved in acute spinal cord injury improve the po- tential for therapeutic intervention? Curr Opin Neurol 2002;15:713-720.
5. Fehlings MG. Summary statement: the use of meth- ylprednisolone in acute spinal cord injury. Spine 2001;26:S55.
6. Schwab ME. Repairing the injured spinal cord. Science (New York, N.Y.) 2002;295:1029-1031.
7. Tator CH. Review of experimental spinal cord injury with emphasis on the local and systemic circulatory effects. Neurochirurgie 1991;37:291-302.
8. Lasfargues JE, Custis D, Morrone F, et al. A model for estimating spinal cord injury prevalence in the United States. Paraplegia 1995;33:62-68.

9. Dryden DM, Saunders LD, Rowe BH, et al. The epi- demiology of traumatic spinal cord injury in Alberta, Canada. Can J Neurol Sci 2003;30:113-121.
10. Griffin MR, Opitz JL, Kurland LT, et al. Traumatic spi- nal cord injury in Olmsted County, Minnesota, 1935- 1981. Am J Epidemiol 1985;121:884-895.
11. Pagliacci MC, Celani MG, Zampolini M, et al. An Ital- ian survey of traumatic spinal cord injury. The Gruppo Italiano Studio Epidemiologico Mielolesioni study. Arch Phys Med Rehabil 2003;84:1266-1275.
12. Karacan I, Koyuncu H, Pekel O, et al. Traumatic spi- nal cord injuries in Turkey: a nation-wide epidemio- logical study. Spinal cord 2000;38:697-701.
13. Citterio A, Franceschini M, Spizzichino L, et al. Non- traumatic spinal cord injury: an Italian survey. Arch Phys Med Rehabil 2004;85:1483-1487.
14. Allen AR: Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture disloca- tion of spinal column. A preliminary report :. J.A.M.A. 1911.;57:878-880.
15. Kaptanoğlu E. Omurilik yaralanmasının patofizyolo- jisi,, Vol. cilt 2 Ankara: Temel Nöroşirürji 2010:, 1623- 1635 , pp.
16. Anderson DK, Means ED, Waters TR, Green ES. Mi- crovascular perfusion and metabolism in injured spi- nal cord after methylprednisolone treatment. J Neuro- surg 1982;56:106-113.
17. Fehlings MG, Sekhon LH, Tator C. The role and timing of decompression in acute spinal cord injury: what do we know? What should we do? Spine 2001;26:S101- 110.
18. Tator CH, Fehlings MG. Review of the secondary in- jury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991;75:15- 26.
19. Young W. Secondary injury mechanisms in acute spi- nal cord injury. J Emerg Med 1993;11 Suppl 1:13-22.
20. Anthes DL, Theriault E, Tator CH. Ultrastructural evi- dence for arteriolar vasospasm after spinal cord trau- ma. Neurosurgery 1996;39:804-814.
21. Holtz A, Nystrom B, Gerdin B. Relation between spinal cord blood flow and functional recovery after blocking weight-induced spinal cord injury in rats. Neurosur- gery 1990;26:952-957.
22. Koyanagi I, Tator CH, Lea PJ. Three-dimensional analysis of the vascular system in the rat spinal cord with scanning electron microscopy of vascular corro- sion casts. Part 2: Acute spinal cord injury. Neurosur- gery 1993;33:285-291; discussion 292.
23. Amar AP, Levy ML. Pathogenesis and pharmaco- logical strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery 1999;44:1027- 1039; discussion 1039-1040.
24. Choi WS, Lee EH, Chung CW, et al. Cleavage of Bax is mediated by caspase-dependent or -independent calpain activation in dopaminergic neuronal cells: protective role of Bcl-2. J Neurochem 2001;77:1531- 1541.
25. Eaton MJ. Cell and molecular approaches to the at- tenuation of pain after spinal cord injury. J Neurotrau- ma 2006;23:549-559.
26. Zhang Z, Guth L. Experimental spinal cord injury: Wal- lerian degeneration in the dorsal column is followed by revascularization, glial proliferation, and nerve re- generation. Exp Neurol 1997;147:159-171.
27. Lou J, Lenke LG, Ludwig FJ, O’Brien MF. Apopto- sis as a mechanism of neuronal cell death following acute experimental spinal cord injury. Spinal cord 1998;36:683-690.
28. Dumont RJ, Okonkwo DO, Verma S, et al. Acute spi- nal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 2001;24:254-264.
29. Guha A, Tator CH, Rochon J. Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats. Stroke 1989;20:372-377.
30. Dolan EJ, Tator CH. The effect of blood transfusion, dopamine, and gamma hydroxybutyrate on post- traumatic ischemia of the spinal cord. J Neurosurg
31. Sandler AN, Tator CH. Review of the effect of spinal cord trama on the vessels and blood flow in the spinal cord. J Neurosurg 1976;45:638-646.
32. Kirshblum SC, Groah SL, McKinley WO, et al. Spinal cord injury medicine. 1. Etiology, classification, and acute medical management. Arch Phys Med Rehabil 2002;83:S50-57, s90-58.
33. Kaptanoglu E, Beskonakli E, Solaroglu I, et al. Mag- nesium sulfate treatment in experimental spinal cord injury: emphasis on vascular changes and early clini- cal results. Neurosurg Rev 2003;26:283-287.
34. Agrawal SK, Nashmi R, Fehlings MG. Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal cord white matter injury. Neurosci- ence 2000;99:179-188.
35. Schwab ME, Bartholdi D. Degeneration and regen- eration of axons in the lesioned spinal cord. Physiol Rev 1996;76:319-370.
36. Kaptanoglu E, Beskonakli E, Okutan O, et al. Effect of magnesium sulphate in experimental spinal cord in- jury: evaluation with ultrastructural findings and early clinical results. J Clin Neurosci 2003;10:329-334.
37. Bracken MB, Holford TR. Effects of timing of methyl- prednisolone or naloxone administration on recovery of segmental and long-tract neurological function in NASCIS 2. J Neurosurg 1993;79:500-507.
38. Nashmi R, Fehlings MG. Mechanisms of axonal dys- function after spinal cord injury: with an emphasis on the role of voltage-gated potassium channels. Brain Res Brain Res Rev 2001;38:165-191.
39. Guha A, Tator CH, Piper I. Effect of a calcium chan- nel blocker on posttraumatic spinal cord blood flow. J Neurosurg 1987;66:423-430.
40. Lucas JH, Wang GF, Gross GW. NMDA antagonists prevent hypothermic injury and death of mammalian spinal neurons. J Neurotrauma 1990;7:229-236.
41. Faden AI. Pharmacotherapy in spinal cord injury: a critical review of recent developments. Clin Neuro- pharmacol 1987;10:193-204.
42. Hall ED, Wolf DL. A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spi- nal cord ischemia. J Neurosurg 1986;64:951-961.
43. Ross IB, Tator CH, Theriault E. Effect of nimodip- ine or methylprednisolone on recovery from acute experimental spinal cord injury in rats. Surg Neurol 1993;40:461-470.
44. Fehlings MG, Tator CH, Linden RD. The effect of ni- modipine and dextran on axonal function and blood flow following experimental spinal cord injury. J Neu- rosurg 1989;71:403-416.
45. Heffner JE, Repine JE. Pulmonary strategies of an- tioxidant defense. Am Rev Respir Dis 1989;140:531- 554.
46. Genovese T, Mazzon E, Di Paola R, et al. Increased oxidative-related mechanisms in the spinal cord injury in old rats. Neurosci Lett 2006;393:141-146.
47. Fujimoto T, Nakamura T, Ikeda T, et al. Effects of EPC- K1 on lipid peroxidation in experimental spinal cord injury. Spine 2000;25:24-29.
48. Kaptanoglu E, Sen S, Beskonakli E, et al. Antioxidant actions and early ultrastructural findings of thiopental and propofol in experimental spinal cord injury. J Neu- rosurg Anesthesiol 2002;14:114-122.
49. Kaptanoglu E, Solaroglu I, Okutan O, et al. Erythro- poietin exerts neuroprotection after acute spinal cord injury in rats: effect on lipid peroxidation and early ultrastructural findings. Neurosurg Rev 2004;27:113- 120.
50. Kaptanoglu E, Tuncel M, Palaoglu S, et al. Compari- son of the effects of melatonin and methylpredniso- lone in experimental spinal cord injury. J Neurosurg 2000;93:77-84.
51. Faden AI, Jacobs TP, Smith MT, Zivin JA. Naloxone in experimental spinal cord ischemia: dose-response studies. Eur J Pharmacol 1984;103:115-120.
52. Faden AI, Jacobs TP, Holaday JW. Comparison of early and late naloxone treatment in experimental spi- nal injury. Neurology 1982;32:677-681.
53. Balentine JD. Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest 1978;39:236-253.
54. Bethea JR, Dietrich WD. Targeting the host inflam- matory response in traumatic spinal cord injury. Curr Opin Neurol 2002;15:355-360.
55. Faden AI, Simon RP. A potential role for excitotoxins in the pathophysiology of spinal cord injury. Ann Neurol 1988;23:623-626.
56. Yanase M, Sakou T, Fukuda T. Role of N-methyl-D- aspartate receptor in acute spinal cord injury. J Neu- rosurg 1995;83:884-888.
57. Agrawal SK, Fehlings MG. Role of NMDA and non- NMDA ionotropic glutamate receptors in traumatic spinal cord axonal injury. J Neurosci 1997;17:1055- 1063.
58. Wrathall JR, Choiniere D, Teng YD. Dose-dependent reduction of tissue loss and functional impairment af- ter spinal cord trauma with the AMPA/kainate antago- nist NBQX. J Neurosci 1994;14:6598-6607.
59. Liu D, Thangnipon W, McAdoo DJ. Excitatory amino acids rise to toxic levels upon impact injury to the rat spinal cord. Brain Res 1991;547:344-348.
60. Emery E, Aldana P, Bunge MB, et al. Apoptosis af- ter traumatic human spinal cord injury. J Neurosurg
61. Shuman SL, Bresnahan JC, Beattie MS. Apoptosis of microglia and oligodendrocytes after spinal cord con- tusion in rats. J Neurosci Res 1997;50:798-808.
62. Crowe MJ, Bresnahan JC, Shuman SL, et al. Apopto- sis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med 1997;3:73-76.
63. Ozawa H, Keane RW, Marcillo AE, et al. Therapeutic strategies targeting caspase inhibition following spinal cord injury in rats. Exp Neurol 2002;177:306-313.