Top

Published in:

01-02-2008 | Original Article

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

Authors: Noboru Hosaka, Shinji Kimura, Akiyoshi Yamazaki, Xianjun Wang, Hiroshi Denda, Takui Ito, Toru Hirano, Naoto Endo

Published in: European Spine Journal | Issue 2/2008

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 NO_x (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 NO_x 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). NO_x 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 NO_x levels between the CCI group (NO_x levels: 5.9 ± 0.7 μM) and the 36 control subjects (1 volunteer and 35 patients without neurologic disorders, NO_x levels: 4.9 ± 0.3 μM). There was no significant difference in NO_x levels and MRP between the non-operated group and the operated group. The NO_x levels in total SCI group were significantly correlated with the ASIA MS and MRP. There was a significant correlation between CSF NO_x levels and neurologic severity or recovery in incomplete CCI.

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

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 130:271–282PubMedCrossRef

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 76:23–31PubMed

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 3:73–76PubMedCrossRef

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

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

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 21:614–619PubMedCrossRef

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 89:911–920PubMed

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

10.

Fehlings MG, Sekhon LH, Tator CH (2001) The role and timing of decompression in acute spinal cord injury. Spine 26:S101–S110PubMedCrossRef

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 7:179–192PubMed

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

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 20:1–9PubMedCrossRef

14.

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

15.

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

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 21:2345–2351PubMedCrossRef

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 18:8551–8558PubMed

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 275:199–202PubMedCrossRef

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 10:275–279PubMedCrossRef

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 92:363–371PubMedCrossRef

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 5:10–11CrossRef

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

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 364:626–632PubMedCrossRef

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 80:1391–1396PubMedCrossRef

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 35:266–274PubMedCrossRef

26.

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

27.

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

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 11:1467–1474CrossRef

29.

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

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 44:785–793PubMedCrossRef

31.

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

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 145:89–95PubMedCrossRef

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 18:523–532PubMedCrossRef

Title: Significant correlation between cerebrospinal fluid nitric oxide concentrations and neurologic prognosis in incomplete cervical cord injury
Authors: Noboru Hosaka
Shinji Kimura
Akiyoshi Yamazaki
Xianjun Wang
Hiroshi Denda
Takui Ito
Toru Hirano
Naoto Endo
Publication date: 01-02-2008
Publisher: Springer-Verlag
Published in: European Spine Journal / Issue 2/2008
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-007-0477-9

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2008

The effects of a 5-HT2A receptor antagonist on blood flow in lumbar disc herniation : application of nucleus pulposus in a canine model

Scoliosis correction with pedicle screws in Duchenne muscular dystrophy

A survey of the “surgical and research” articles in the European Spine Journal, 2007

Vertebral endplate trauma induces disc cell apoptosis and promotes organ degeneration in vitro

Pain and disability correlated with disc degeneration via magnetic resonance imaging in scoliosis patients

The positive effect of posterolateral lumbar spinal fusion is preserved at long-term follow-up: a RCT with 11–13 year follow-up