Abstract
The role of oxidative stress in spinal cord injury (SCI) induced upregulation of constitutive or inducible isoforms of nitric oxide synthase (cNOS or iNOS) is not well known. The present investigation was undertaken to examine the influence of an antioxidant compound H-290/51 (Astra-Zeneca, Molndal, Sweden) on SCI induced cNOS and iNOS upregulation in a rat model. SCI induced by incision into the right dorsal horn of the T10–11 segment resulted in marked NOS upregulation. Upregulation of cNOS was most prominent in the uninjured T9 and T12 segments. On the other hand, iNOS expression was most marked in the injured T10–11 segments. These NOS immunoreactivities were mainly confined to the injured cells located in the edematous regions of the cord exhibiting profound leakage of Evans blue and [131]Iodine-sodium tracers. Pretreatment with H-290/51 markedly attenuated the trauma-induced cNOS and iNOS expression along with the microvascular permeability disturbances, edema formation and cell injury. These results suggest that (i) oxidative stress is involved in SCI induced induction of cNOS and iNOS, (ii) NO plays an important role in the cord pathology, and (iii) that the compound H-290/51 has a potential therapeutic value in SCI.
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References
Chiueh CC, Gilbert DL, Colton CA (1994) The neurobiology of NO and OH. Ann NY Acad Sci 738: 1–471
Choi DW (1993) Nitric oxide: foe or friend to the injured brain. Proc Natl Acad Sci USA 90: 9741–9743
Dawson VL, Dawson TM (1996) Nitric oxide neurotoxicity. J Chem Neuroanat 10: 179–190
Faden AI, Halt P (1992) Platelet-activating factor reduces spinal cord blood flow and causes behavioral deficits after intrathecal administration in rats through a specific receptor mechanism. J Pharmacol Exp Ther 261: 1064–1070
Frerichs KU, Feuerstein GZ (1990) Platelet-activating factor; key mediat or in neuro injury? Cerebrovasc Brain Metab Rev 2: 148–160
Fukuda K, Richmon JD, Sato M, Sharp FR, Panter SS, Noble LJ (1996b) Induction of heme oxygenase-1 (HO-1) in glia after traumatic brain injury. Brain Res 736: 68–95
Kimura H, Steinbusch HWM (1996) The role of nitric oxide in the central nervous system. From basic to therapeutic aspect. J Chem Neuroanat 10: 179–322
McCord JM (1987) Oxygen-derivated radicals: a link between reperfusion injury and inflammation. Federation Proc 46: 2402–2406
Misra HP, Fridovich I (1972) The role of superoxide an ion in the auto-oxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247: 3170–3175
Mustafa A, Sharma HS, Olsson Y, Gordh T, Thorén P, Sjöquist P-O, Roos P, Adem A, Nyberg F (1995) Vascular permeability to growth hormone in the rat central nervous system after focal spinal cord injury. Influence of a new antioxidant compound H290/51 and age. Neurosci Res 23: 185–194
Novikov L, Novikova L, Kellerth J-O (1995) Brain-derived neurotrophic factor promotes survival and blocks nitric oxide synthase expression in adult rat spinal motoneurons after ventral nerve root avulsion. Neurosci Lett 200: 45–48
Sharma HS (1987) Effect of captopril (a converting enzyme inhibitor) on blood-brain barrier permeability and cerebral blood flow in normotensive rats. Neuropharmacology 26: 85–92
Sharma HS, Olsson Y (1990) Edema formation and cellular alterations following spinal cord injury in rat and their modification with p-chlorophenylalanine. Acta Neuropathol (Berlin) 79: 604–610
Sharma HS, Cervós-Navarro J, Dey PK (1991) Rearing at high ambient temperature during later phase of the brain development enhances functional plasticity of the CNS and induces tolerance to heat stress. An experimental study in the conscious normotensive young rats. Brain Dysfunction 4: 104–124
Sharma HS, Olsson Y, Dey PK (1990) Early accumulation of serotonin in rat spinal cord subjected to traumatic injury. Relation to edema and blood flow changes. Neuroscience 36: 725–730
Sharma HS, Westman J, Olsson Y, Alm P (1996) Involvement of nitric oxide in acute spinal cord injury: an immunohistochemical study using light and electron microscopy in the rat. Neurosci Res 24: 373–384
Sharma HS, Westman J, Alm P, Sjöquist P-O, Cervjós-Navarro J, Nyberg F (1997) Involvement of nitric oxide in the pathophysiology of acute heat stress in the rat. Ann NY Acad Sci 813: 581–590
Sharma HS, Nyberg F, Gordh T, Alm P, Westman J (1997) Topical application of insulin like growth factor-1 reduces edema and upregulation of neuronal nitric oxide synthase following trauma to the rat spinal cord. Acta Neurochir Suppl 70: 130–133
Sharma HS, Alm P, Westman J (1998) Nitric oxide and carbon monoxide in the pathophysiology of brain functions in heat stress. Brain functions in hot environment. In: Sharma HS, Westman J (eds) Progr Brain Res 115: 297–333
Sharma HS, Nyberg F, Gordh T, Aim P, Westman J (1998) Neurotrophic factors attenuate neuronal nitric oxide synthase upregulation, microvascular permeability disturbances, edema formation and cell injury in the spinal cord following trauma. Spinal cord monitoring. In: Stålberg E, Sharma HS, Olsson Y (eds) Springer, Wien New York, pp 181–210
Sharma HS, Westman J, Nyberg F (1998) Pathophysiology of brain edema and cell changes following hyperthermic brain injury. Brain functions in hot environment. In: Sharma HS, Westman J (eds) Progr Brain Res 115: 351–412
Sharma HS, Sjjöquist P-O, Westman J (2001) Pathophysiology of the blood-spinal cord barrier in spinal cord injury. Influence of a new antioxidant compound H-290/51. In: Kobiler D, Lustig S, Shapra S (eds) Blood-brain barrier. Drug Delivery and Brain Pathology. Kluwer Academic/Plenum Publishers, New York, pp 401–416
Svensson L, Björjesson I, Kull B, Sjöquist P-O (1993) Automated procedure for measuring TBARS for in vitro comparison of the effect of antioxidants on tissues. Scand J C1in Lab Invest 53: 83–85
Winkler T, Sharma HS, Stålberg E, Westman (1998) Spinal cord bioelectrical activity, edema and cell injury following a focal trauma to the spinal cord. An experimental study using pharmacological and morphological approach. Spinal cord monitoring. In: Stålberg E, Sharma HS, Olsson Y (eds) Springer, Wien New York, pp 283–363
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Sharma, H.S., Sjöquist, PO., Alma, P. (2003). A new antioxidant compound H-290/51 attenuates spinal cord injury induced expression of constitutive and inducible isoforms of nitric oxide synthase and edema formation in the rat. In: Kuroiwa, T., et al. Brain Edema XII. Acta Neurochirurgica Supplements, vol 86. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0651-8_86
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DOI: https://doi.org/10.1007/978-3-7091-0651-8_86
Publisher Name: Springer, Vienna
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