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Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

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IMPACT FACTOR 2016 (Open Life Sciences): 0.448

CiteScore 2016: 1.02

SCImago Journal Rank (SJR) 2016: 0.329
Source Normalized Impact per Paper (SNIP) 2016: 0.621

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ISSN
2391-5412
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Volume 7, Issue 6 (Dec 2012)

Issues

Protective effects of glucosamine-kynurenic acid after compression-induced spinal cord injury in the rat

Andrea Korimová / Dáša Cížková / Jozsef Toldi / László Vécsei / Ivo Vanický
Published Online: 2012-10-10 | DOI: https://doi.org/10.2478/s11535-012-0096-2

Abstract

Kynurenic acid (KYNA), a metabolite of the essential amino acid L-tryptophan, is a broad spectrum antagonist of excitatory amino acid receptors, which have also anticonvulsant and neuroprotective properties. After spinal cord injury (SCI), excitotoxicity is considered to play a significant role in the processes of secondary tissue destruction in both grey and white matter of the spinal cord. In this study, we have tested the potential therapeutic effect of glucosamine-kynurenic acid, administered after experimental compression-induced SCI in the rat. Spinal application of glucosamine-kynurenic acid continually for 24 hr after experimental SCI resulted in improved motor function recovery, beginning from the first week of evaluation and continuing until the end of the study (4 weeks). After 4 weeks’ survival, quantitative morphometric analysis of the spinal cord showed that glucosamine-kynurenic acid treatment was associated with improved tissue preservation at the lesion site. These findings indicate that spinal application of glucosaminekynurenic acid is neuroprotective and improves the outcome even when administered after spinal trauma. Our results suggest that the treatments initiated in early posttraumatic period can alleviate secondary injury and improve the final outcome after SCI.

Keywords: Spinal cord injury; Excitotoxicity; NMDA receptor; Kynurenic acid

  • [1] Crowe M.J., Bresnahan J.C., Shuman S.L., Masters J.N., Beattie M.S., Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys, Nat. Med., 1997, 3, 73–76 http://dx.doi.org/10.1038/nm0197-73CrossrefGoogle Scholar

  • [2] Tator C.H., Fehlings M.G., Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms, J. Neurosurg., 1991,75, 15–26 http://dx.doi.org/10.3171/jns.1991.75.1.0015CrossrefGoogle Scholar

  • [3] Fitch M.T., Doller C., Combs C.K., Landreth G.E., Silver J., Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma, J. Neurosci., 1999, 19, 8182–8198 Google Scholar

  • [4] Nelson E., Gertz S.D., Rennels M.L., Ducker T.B., Blaumanis O.R., Spinal cord injury. The role of vascular damage in the pathogenesis of central hemorrhagic necrosis, Arch. Neurol., 1977, 34, 332–333 http://dx.doi.org/10.1001/archneur.1977.00500180026005CrossrefGoogle Scholar

  • [5] Taoka Y., Okajima K., Spinal cord injury in the rat, Prog. Neurobiol., 1998, 56, 341–358 http://dx.doi.org/10.1016/S0301-0082(98)00049-5CrossrefGoogle Scholar

  • [6] Liu X.Z., Xu X.M., Hu R., Du C., Zhang S.X., McDonald J.W., et al., Neuronal and glial apoptosis after traumatic spinal cord injury, J. Neurosci., 1997, 17, 5395–5406 Google Scholar

  • [7] Tator C.H., Koyanagi I., Vascular mechanisms in the pathophysiology of human spinal cord injury, J. Neurosurg., 1997, 86, 483–492 CrossrefGoogle Scholar

  • [8] Balentine J.D., Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury, Lab. Invest., 1978, 39, 236–253 Google Scholar

  • [9] Kwon B.K., Okon E., Hillyer J., Mann C., Baptiste D., Weaver L.C., et al., A systematic review of noninvasive pharmacologic neuroprotective treatments for acute spinal cord injury, J. Neurotrauma, 2011, 28, 1545–1588 http://dx.doi.org/10.1089/neu.2009.1149CrossrefGoogle Scholar

  • [10] Bracken M.B., Shepard M.J., Collins W.F., Holford T.R., Young W., Baskin D.S., et al., A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study, N. Engl. J. Med., 1990, 322, 1405–1411 http://dx.doi.org/10.1056/NEJM199005173222001CrossrefGoogle Scholar

  • [11] Short D.J., El Masry W.S., Jones P.W., High dose methylprednisolone in the management of acute spinal cord injury — a systematic review from a clinical perspective, Spinal Cord, 2000, 38, 273–286 http://dx.doi.org/10.1038/sj.sc.3100986CrossrefGoogle Scholar

  • [12] McAdoo D.J., Xu G.Y., Robak G., Hughes M.G., Changes in amino acid concentrations over time and space around an impact injury and their diffusion through the rat spinal cord, Exp. Neurol., 1999, 159, 538–544 http://dx.doi.org/10.1006/exnr.1999.7166CrossrefGoogle Scholar

  • [13] Ikonomidou C., Turski L., Excitotoxicity and neurodegenerative diseases, Curr. Opin. Neurol., 1995, 8, 487–497 http://dx.doi.org/10.1097/00019052-199512000-00017CrossrefGoogle Scholar

  • [14] Muir K.W., Lees K.R., Clinical experience with excitatory amino acid antagonist drugs, Stroke, 1995, 26, 503–513 http://dx.doi.org/10.1161/01.STR.26.3.503CrossrefGoogle Scholar

  • [15] Stone T.W., Kynurenines in the CNS: from endogenous obscurity to therapeutic importance, Prog. Neurobiol., 2001, 64, 185–218 http://dx.doi.org/10.1016/S0301-0082(00)00032-0CrossrefGoogle Scholar

  • [16] Birch P.J., Grossman C.J., Hayes A.G., Kynurenic acid antagonises responses to NMDA via an action at the strychnine-insensitive glycine receptor, Eur. J. Pharmacol., 1988, 154, 85–87 http://dx.doi.org/10.1016/0014-2999(88)90367-6CrossrefGoogle Scholar

  • [17] Schwarcz R., Pellicciari R., Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities, J. Pharmacol. Exp. Ther., 2002, 303, 1–10 http://dx.doi.org/10.1124/jpet.102.034439CrossrefGoogle Scholar

  • [18] Hilmas C., Pereira E.F., Alkondon M., Rassoulpour A., Schwarcz R., Albuquerque E.X., The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications, J. Neurosci., 2001, 21, 7463–7473 Google Scholar

  • [19] Wang J., Zhao X., Zheng Y., Kong H., Lu G., Cai Z., et al., Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35, J. Biol. Chem., 2006, 281, 22021–22028 http://dx.doi.org/10.1074/jbc.M603503200CrossrefGoogle Scholar

  • [20] Wrathall J.R., Bouzoukis J., Choiniere D., Effect of kynurenate on functional deficits resulting from traumatic spinal cord injury, Eur. J. Pharmacol., 1992, 218, 273–281 http://dx.doi.org/10.1016/0014-2999(92)90179-8CrossrefGoogle Scholar

  • [21] Fuvesi J., Somlai C., Nemeth H., Varga H., Kis Z., Farkas T., et al., Comparative study on the effects of kynurenic acid and glucosamine-kynurenic acid, Pharmacol. Biochem. Behav., 2004, 77, 95–102 http://dx.doi.org/10.1016/j.pbb.2003.10.001CrossrefGoogle Scholar

  • [22] Nemeth H., Toldi J., Vecsei L., Role of kynurenines in the central and peripheral nervous systems, Curr. Neurovasc. Res., 2005, 2, 249–260 http://dx.doi.org/10.2174/1567202054368326CrossrefGoogle Scholar

  • [23] Vanicky I., Urdzikova L., Saganova K., Cizkova D., Galik J., A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat, J. Neurotrauma, 2001, 18, 1399–13407 http://dx.doi.org/10.1089/08977150152725687CrossrefGoogle Scholar

  • [24] Basso D.M., Beattie M.S., Bresnahan J.C., A sensitive and reliable locomotor rating scale for open field testing in rats, J. Neurotrauma, 1995, 12, 1–21 http://dx.doi.org/10.1089/neu.1995.12.1CrossrefGoogle Scholar

  • [25] Herzog A., Brosamle C., ’semifree-floating’ treatment: a simple and fast method to process consecutive sections for immunohistochemistry and neuronal tracing, J. Neurosci. Methods, 1997, 72, 57–63 http://dx.doi.org/10.1016/S0165-0270(96)00156-2CrossrefGoogle Scholar

  • [26] Liu D., Thangnipon W., McAdoo D.J., Excitatory amino acids rise to toxic levels upon impact injury to the rat spinal cord, Brain Res., 1991, 547, 344–348 http://dx.doi.org/10.1016/0006-8993(91)90984-4CrossrefGoogle Scholar

  • [27] Painter S.C., Wum S.W., Faden A.I., Alteration in extracellular amino acids after traumatic spinal cord injury, Ann. Neurol., 1990, 27, 96–99 http://dx.doi.org/10.1002/ana.410270115CrossrefGoogle Scholar

  • [28] Mody I., MacDonald J.F., NMDA receptordependent excitotoxicity: the role of intracellular Ca2+ release, Trends Pharmacol. Sci., 1995, 16, 356–359 http://dx.doi.org/10.1016/S0165-6147(00)89070-7CrossrefGoogle Scholar

  • [29] Hall E.D., Springer J.E., Neuroprotection and acute spinal cord injury: a reappraisal, NeuroRx., 2004, 1, 80–100 http://dx.doi.org/10.1602/neurorx.1.1.80CrossrefGoogle Scholar

  • [30] Robotka H., Németh H., Somlai C., Vécsei L., Toldi J., Systemically administered glucosaminekynurenic acid, but not pure kynurenic acid, is effective in decreasing the evoked activity in area CA1 of the rat hippocampus, Eur. J. Pharmacol., 2005, 513, 75–80 http://dx.doi.org/10.1016/j.ejphar.2005.02.043CrossrefGoogle Scholar

  • [31] Faden A.I., Ellison J.A., Noble L.J., Effects of competitive and non-competitive NMDA receptor antagonists in spinal cord injury, Eur. J. Pharmacol., 1990, 175, 165–174 http://dx.doi.org/10.1016/0014-2999(90)90227-WCrossrefGoogle Scholar

  • [32] Wrathall J.R., Choiniere D., Teng Y.D., Dosedependent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/ kainate antagonist NBQX, J. Neurosci., 1994, 14, 6598–6607 Google Scholar

  • [33] McAdoo D.J., Wu P., Microdialysis in central nervous system disorders and their treatment, Pharmacol. Biochem. Behav., 2008, 90, 282–296 http://dx.doi.org/10.1016/j.pbb.2008.03.001CrossrefGoogle Scholar

  • [34] Carriedo S.G., Yin H. Z., Sensi S. L., Weiss J. H. (1998) Rapid Ca2+ entry through Ca2+-permeable AMPA/Kainate channels triggers marked intracellular Ca2+ rises and consequent oxygen radical production, J. Neurosci., 1998, 18, 7727–7738 Google Scholar

  • [35] Doble A., The role of excitotoxicity in neurodegenerative disease: implications for therapy, Pharmacol. Ther., 1999, 81, 163–221 http://dx.doi.org/10.1016/S0163-7258(98)00042-4CrossrefGoogle Scholar

  • [36] Choi W.D., Excitotoxic cell death, J. Neurobiol., 1992, 23, 1261–1276 http://dx.doi.org/10.1002/neu.480230915CrossrefGoogle Scholar

  • [37] Choi W.D., Glutamate neurotoxicity and diseases of the nervous system, Neuron, 1998, 1, 623–634 http://dx.doi.org/10.1016/0896-6273(88)90162-6CrossrefGoogle Scholar

  • [38] Li S., Mealing G.A., Morley P., Stys P.K., Novel injury mechanism in anoxia and trauma of spinal cord white matter: glutamate release via reverse Na+-dependent glutamate transport, J. Neurosci., 1999, 19, RC16 Google Scholar

  • [39] Li S., Stys P.K., Mechanisms of ionotropic glutamate receptor-mediated excitotoxicity in isolated spinal cord white matter, J. Neurosci., 2000, 20, 1190–1198 Google Scholar

  • [40] Rosenberg L.J., Teng Y.D., Wrathall J.R., 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f) quinoxaline reduces glial loss and acute white matter pathology after experimental spinal cord contusion, J. Neurosci., 1999, 19, 464–475 Google Scholar

About the article

Published Online: 2012-10-10

Published in Print: 2012-12-01


Citation Information: Open Life Sciences, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-012-0096-2.

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© 2012 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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