Skip to main content

Advertisement

Log in

Significant correlation between cerebrospinal fluid nitric oxide concentrations and neurologic prognosis in incomplete cervical cord injury

  • Original Article
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

In animal models of spinal cord injury (SCI), inducible NO (nitric oxide) synthase is expressed in the spinal cord immediately after sustaining SCI. Excessive NO production has cytotoxic effects and induces neuronal apoptosis, causing neural degeneration and neurodysfunction in the spinal cord. Little is known, however, about the relationship between NOx (NO metabolites: nitrite and nitrate) levels in the cerebrospinal fluid (CSF) and neurologic severity or recovery in clinical cases. The objective of the present study was to examine the correlation between CSF NOx levels and neurologic severity or recovery in SCI. Twenty-five patients with incomplete cervical cord injury (CCI) were examined. Eight cases were treated conservatively (non-operated group). Seventeen cases underwent surgical intervention (operated group). NOx levels in the CSF were measured using the Griess method. The severity of the neurologic impairment was assessed using Frankel’s classification and the American Spinal Injury Association motor score (ASIA MS). The degree of neurologic recovery was assessed using Frankel’s classification and the ASIA motor recovery percentage (MRP). There was no significant difference in the NOx levels between the CCI group (NOx levels: 5.9 ± 0.7 μM) and the 36 control subjects (1 volunteer and 35 patients without neurologic disorders, NOx levels: 4.9 ± 0.3 μM). There was no significant difference in NOx levels and MRP between the non-operated group and the operated group. The NOx levels in total SCI group were significantly correlated with the ASIA MS and MRP. There was a significant correlation between CSF NOx levels and neurologic severity or recovery in incomplete CCI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bao F, Liu D (2002) Peroxynitrite generated in the rat spinal cord induces neuron death and neurological deficits. Neuroscience 115:839–849

    Article  PubMed  CAS  Google Scholar 

  2. Blum JW, Morel C, Hammon HM, Bruckmaier RM, Jaggy A, Zurbriggen A, Jungi T (2001) High constitutional nitrate status in young cattle. Comp Biochem Physiol A Mol Integr Physiol 130:271–282

    Article  PubMed  CAS  Google Scholar 

  3. Bracken MB, Shepard MJ, Collins WF Jr, Holford TR, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon JC, Marshall LF et al (1992) Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second national acute spinal cord injury study. J Neurosurg 76:23–31

    PubMed  CAS  Google Scholar 

  4. Crowe MJ, Bresnahan JC, Shuman SL, Masters JN, Beattie MS (1997) Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med 3:73–76

    Article  PubMed  CAS  Google Scholar 

  5. Dawson VL, Dawson TM, Bartley DA, Uhl GR, Snyder SH (1993) Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci 13:2651–2661

    PubMed  CAS  Google Scholar 

  6. El Masry WS, Katoh S, Khan A (1993) Reflections on the neurological significance of bony canal encroachment following traumatic injury of the spine in patients with Frankel C, D, and E presentation. J Neurotrauma 10(1 Suppl):S70

    Google Scholar 

  7. El Masry WS, Tsubo M, Katoh S, El Miligui YH, Khan A (1996) Validation of the American spinal injury association (ASIA) motor score and the national acute spinal cord injury study (NASCIS) motor score. Spine 21:614–619

    Article  PubMed  CAS  Google Scholar 

  8. Emery E, Aldana P, Bunge MB, Puckett W, Srinivasan A, Keane RW, Bethea J, Levi AD (1998) Apoptosis after traumatic human spinal cord injury. J Neurosurg 89:911–920

    PubMed  CAS  Google Scholar 

  9. Estevetz AG, Spear N, Manuel SM, Radi R, Henderson CE, Barbeito L, Beckman JS (1998) Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation. J Neurosci 18:923–931

    Google Scholar 

  10. Fehlings MG, Sekhon LH, Tator CH (2001) The role and timing of decompression in acute spinal cord injury. Spine 26:S101–S110

    Article  PubMed  CAS  Google Scholar 

  11. Frankel HL, Hancock DO, Hyslop G, Melzak J, Michaelis LS, Ungar GH, Vernon JD, Walsh JJ (1969) The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia. Part 1. Paraplegia 7:179–192

    PubMed  CAS  Google Scholar 

  12. Griess JP (1964) On a new series of bodies in which nitrogen is substituted for hydrogen. Philos Trans R Soc Lond 154:667–731

    Google Scholar 

  13. 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 20:1–9

    Article  PubMed  CAS  Google Scholar 

  14. Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94

    Article  PubMed  CAS  Google Scholar 

  15. Isaksson J, Farooque M, Olsson Y (2005) Improved functional outcome after spinal cord injury in iNOS-deficient mice. Spinal Cord 43:167–170

    Article  PubMed  CAS  Google Scholar 

  16. Katoh S, El Masry WS, Jaffray D, McCall IW, Eisenstein SM, Pringle RG, Pullicino V, Ikata T (1996) Neurological outcome in conservatively treated patients with incomplete closed traumatic cervical spinal cord injuries. Spine 21:2345–2351

    Article  PubMed  CAS  Google Scholar 

  17. Kimura S, Uchiyama S, Takahashi HE, Shibuki K (1998) cAMP-dependent long-term potentiation of nitric oxide release from cerebellar parallel fibers in rats. J Neurosci 18:8551–8558

    PubMed  CAS  Google Scholar 

  18. Kimura S, Yajiri Y, Uchiyama S, Takahashi HE, Shibuki K (1999) Nitric oxide release from substantia gelatinosa of the rat spinal cord in vitro. Neurosci Lett 275:199–202

    Article  PubMed  CAS  Google Scholar 

  19. Kimura S, Watanabe K, Yajiri Y, Motegi T, Masuya Y, Shibuki K, Uchiyama S, Homma T, Takahashi HE (1999) Cerebrospinal fluid nitric oxide metabolites in painful diseases. NeuroReport 10:275–279

    Article  PubMed  CAS  Google Scholar 

  20. Kimura S, Watanabe K, Yajiri Y, Uchiyama S, Hasegawa K, Shibuki K, Endo N (2001) Cerebrospinal fluid nitric oxide metabolites are novel predictors of pain relief in degenerative lumbar diseases. Pain 92:363–371

    Article  PubMed  CAS  Google Scholar 

  21. Kimura S, Ito T, Watanabe K, Hirano T, Yamazaki A, Imura K (2005) Prediction of postoperative pain relief in degenerative lumbar diseases using CSF nitric oxide metabolites: multiple center study. Spine J 5:10–11

    Article  Google Scholar 

  22. La Rosa G, Cardali S, Genovese T, Conti A, Di Paola R, La Torre D, Cacciola F, Cuzzocrea S (2004) Inhibition of the nuclear factor -κB activation with pyrolidine dithiocarbamate attenuating inflammation and oxidative stress after spinal cord trauma in rats. J Neurosurg Spine 3:311–321

    Google Scholar 

  23. 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 364:626–632

    Article  PubMed  CAS  Google Scholar 

  24. Marino RJ, Ditunno JF Jr, Donovan WH, Maynard F Jr (1999) Neurologic recovery after traumatic spinal cord injury. Data from the model spinal cord injury systems. Arch Phys Med Rehabil 80:1391–1396

    Article  PubMed  CAS  Google Scholar 

  25. Maynard FM Jr, Bracken MB, Creasey G, Ditunno JF Jr, Donovan WH, Ducker TB, Garber SL, Marino RJ, Stover SL, Tator CH, Waters RL, Wilberger JE, Young W (1997) International standards for neurological and functional classification of spinal cord injury. Spinal Cord 35:266–274

    Article  PubMed  Google Scholar 

  26. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide; physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

  27. Moshage H, Kok B, Huizenga JR, Jansen PL (1995) Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 41:892–896

    PubMed  CAS  Google Scholar 

  28. Nakahara S, Yone K, Setoguchi T, Yamaura I, Arishima Y, Yoshino S (2002) Change in nitric oxide synthase in spinal cord after traumatic injury in rats. J Neurotrauma 11:1467–1474

    Article  Google Scholar 

  29. Nishisho T, Tonai T, Tamura Y, Ikata T (1996) Experimental and clinical studies of eicosanoids in cerebrospinal fluid after spinal cord injury. Neurosurg 39:950–957

    Article  CAS  Google Scholar 

  30. Selden NR, Quint DJ, Pate N, Hannah S, Papadopoulos SM (1999) Emergency magnetic resonance imaging of cervical spinal cord injuries: clinical correlation and prognosis. Neurosurgery 44:785–793

    Article  PubMed  CAS  Google Scholar 

  31. Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75:15–26

    Article  PubMed  CAS  Google Scholar 

  32. Wang X, Kimura S, Yazawa T, Endo N (2005) Cerebrospinal fluid sampling by lumbar puncture in rats—repeated measurements of nitric oxide metabolites. J Neurosci Methods 145:89–95

    Article  PubMed  CAS  Google Scholar 

  33. Xu J, Kim GM, Chen S, Yan P, Ahmed SH, Ku G, Beckman JS, Xu XM, Hsu CY (2001) iNOS and nitrotyrosine expression after spinal cord injury. J Neurotrauma 18:523–532

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Yoshiaki Tanaka for his technical assistance. This study was supported in part by a medical research grant on traffic accidents from The General Insurance Association of Japan. This study was approved by the Ethics Committee of Niigata University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shinji Kimura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hosaka, N., Kimura, S., Yamazaki, A. et al. Significant correlation between cerebrospinal fluid nitric oxide concentrations and neurologic prognosis in incomplete cervical cord injury. Eur Spine J 17, 281–286 (2008). https://doi.org/10.1007/s00586-007-0477-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-007-0477-9

Keywords

Navigation