Abstract
The secondary pathological changes following mechanical trauma to the spinal cord cause deterioration of its function, and oxidative stress is known to contribute to the process. The roles of intercellular adhesion molecule-1 (ICAM-l) and nitric oxide in the process were investigated using rat incomplete spinal cord injury model.
ICAM-1mRNA expression reached its maximum at 6 h after SCI. By the intravenous injection of ICAM-1 monoclonal antibody (ICAM-l mAb) after SCI, posttraumatic polynuclear cell infiltration seemed to decrease and motor recovery was enhanced. Nitric oxide (NO) increased in the injured spinal cord. The expression of mRNA of constitutive NOS (c-NOS) did not change, whereas that of inducible NOS (i-NOS) increased after injury. Inhibiting the activity of c-NOS made motor function worse and that of i-NOS enhanced motor recovery.
Lecithinized superoxide dismutase (PC-SOD) was developed to increase half-life and permeability in vivo, and PC-SOD was used in this model to lessen oxidative stress. Intravenous injection of PC-SOD after injury suppressed the expression of IL-1β, ICAM-1, and i-NOS mRNAs, enhanced the expression of mRNA of neurotrophin-3, and caused motor recovery better than methylprednisolone injection.
These results indicated that oxidative stress enhances neuronal damage after mechanical trauma and suggested that it is important to suppress the oxidative stress.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Katoh S, el Masry WS (1994) Neurological recovery after conservative treatment of cervical cord injuries. J Bone Joint Surg Br 76(2):225–228
Janssen L, Hansebout R (1989) Pathogenesis of spinal cord injury and newer treatments. A review. Spine 14
Demopoulos H, Flamm E, Pietronigro D, Sligman M (1980) The free radical pathology and the microcirculation in the major central nervous disorders. Acta Physiol Scand Suppl 492:91–119
Iwasa K, Ikata T, Fukuzawa K (1989) Protective effect of vitamin E on spinal cord injury by compression and concurrent lipid peroxidation. Free Radic Biol Med 6:599–606
Mitsuhashi T, Ikata T, Morimoto K, Tonai T, Katoh S (1994) Increased production of eicosanoids, TXA2, PGI2 and LTC4 in experimental spinal cord injuries. Paraplegia 32(8):524–530
Means ED, Anderson DK (1983) Neuronophagia by leukocytes in experimental spinal cord injury. J Neuropathol Exp Neurol 42(6):707–719
Xu JA, Hsu CY, Liu TH, Hogan EL, Perot PL Jr, Tai HH (1990) Leukotriene B4 release and polymorphonuclear cell infiltration in spinal cord injury. J Neurochem 55(3):907–912
Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, Freeman DF, Wagner FC, Flamm ES, Eisenberg HM, Goodman JH et al (1985) Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the national acute spinal cord injury study. J Neurosurg 63(5):704–713
Bracken M, Shepard M, Collins W, Holford T, Young W, Baskin D, Eisenberg H, Flamm E, Leo-Summers L, Maroon J, Marshall L, Perot PJ, Piepmeier J, Sonntag V, Wagner F, Wilberger J, Winn H (1990) A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of second national acute spinal cord injury study. N Engl J Med 322:1405–1411
Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings MG, 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 (1998) Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third national acute spinal cord injury randomized controlled trial. J Neurosurg 89(5):699–706
Ito Y, Sugimoto Y, Tomioka M, Kai N, Tanaka M (2009) Does high dose methylprednisolone sodium succinate really improve neurological status in patient with acute cervical cord injury?: a prospective study about neurological recovery and early complications. Spine (Phila Pa 1976) 34(20):2121–2124. doi:10.1097/BRS.0b013e3181b613c7
Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H (2001) Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury. Spine 26(4):426–430
Hamada Y, Ikata T, Katoh S, Nakauchi K, Niwa M, Kawai Y, Fukuzawa K (1996) Involvement of an intercellular adhesion molecule 1-dependent pathway in the pathogenesis of secondary changes after spinal cord injury in rats. J Neurochem 66(4):1525–1531
Clark WM, Madden KP, Rothlein R, Zivin JA (1991) Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule. J Neurosurg 75(4):623–627. doi:10.3171/jns.1991.75.4.0623
Zielasek J, Archelos JJ, Toyka KV, Hartung HP (1993) Expression of intercellular adhesion molecule-1 on rat microglial cells. Neurosci Lett 153(2):136–139
Fujita H, Morita I, Murota S (1994) A possible mechanism for vascular endothelial cell injury elicited by activated leukocytes: a significant involvement of adhesion molecules, CD11/CD18, and ICAM-1. Arch Biochem Biophys 309(1):62–69. doi:S000398618471085X [pii]
Hallenbeck JM, Dutka AJ, Tanishima T, Kochanek PM, Kumaroo KK, Thompson CB, Obrenovitch TP, Contreras TJ (1986) Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. Stroke 17(2):246–253
Hamada Y, Ikata T, Katoh S, Tsuchiya K, Niwa M, Tsutsumishita Y, Fukuzawa K (1996) Roles of nitric oxide in compression injury of rat spinal cord. Free Radic Biol Med 20(1):1–9
Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288(5789):373–376
Li P, Tong C, Eisenach JC, Figueroa JP (1994) NMDA causes release of nitric oxide from rat spinal cord in vitro. Brain Res 637(1–2):287–291. doi:0006-8993(94)91246-7 [pii]
Wink DA, Hanbauer I, Laval F, Cook JA, Krishna MC, Mitchell JB (1994) Nitric oxide protects against the cytotoxic effects of reactive oxygen species. Ann N Y Acad Sci 738:265–278
Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A 88(11):4651–4655
Tominaga T, Sato S, Ohnishi T, Ohnishi ST (1993) Potentiation of nitric oxide formation following bilateral carotid occlusion and focal cerebral ischemia in the rat: in vivo detection of the nitric oxide radical by electron paramagnetic resonance spin trapping. Brain Res 614(1–2):342–346
Nakauchi K, Ikata T, Katoh S, Hamada Y, Tsuchiya K, Fukuzawa K (1996) Effects of lecithinized superoxide dismutase on rat spinal cord injury. J Neurotrauma 13(10):573–582
Chikawa T, Ikata T, Katoh S, Hamada Y, Kogure K, Fukuzawa K (2001) Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats: transcriptional regulation of inflammatory and neurotrophic genes. J Neurotrauma 18(1):93–103
McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244(22):6049–6055
Cuevas P, Carceller-Benito F, Reimers D (1989) Administration of bovine superoxide dismutase prevents sequelae of spinal cord ischemia in the rabbit. Anat Embryol (Berl) 179(3):251–255
Igarashi R, Hoshino J, Ochiai A, Morizawa Y, Mizushima Y (1994) Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity. J Pharmacol Exp Ther 271:1672–1677
el Masry WS (1993) Physiological instability of the spinal cord following injury. Paraplegia 31(5):273–275
Katoh S, Ikata T, Tsubo M, Hamada Y, el Masry WS (1997) Possible implication of leukocytes in secondary pathological changes after spinal cord injury. Injury 28(3):215–217
Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364(6438):626–632. doi:10.1038/364626a0
Conflict of Interest All authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Japan
About this chapter
Cite this chapter
Katoh, S., Hamada, Y., Chikawa, T. (2014). Oxidative Stress as Secondary Injury Mechanism After Mechanical Trauma in the Spinal Cord. In: Uchida, K., Nakamura, M., Ozawa, H., Katoh, S., Toyama, Y. (eds) Neuroprotection and Regeneration of the Spinal Cord. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54502-6_18
Download citation
DOI: https://doi.org/10.1007/978-4-431-54502-6_18
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-54501-9
Online ISBN: 978-4-431-54502-6
eBook Packages: MedicineMedicine (R0)