Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 9, December, p. 1329–1334

doi: 10.17219/acem/65478

Publication type: original article

Language: English

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The neuroprotective effect of N-acetylcysteine in spinal cord-injured rats

Edyta Olakowska1,A,B,D, Wiesław Marcol1,A,D, Adam Właszczuk1,B,C, Izabella Woszczycka-Korczyńska1,B,C, Joanna Lewin-Kowalik1,E,F

1 Department of Physiology, Medical University of Silesia, Katowice, Poland

Abstract

Background. Spinal cord injury (SCI) is an important cause of impairment of sensory and motor nerve function. It has been shown that free-radical species play an important role in the pathogenesis of acute tissue trauma after SCI. There are no proven pharmacological therapies that provide neuroprotection and stimulate axonal growth after trauma.
Objectives. The aim of this study was to investigate the neuroprotective effect of N-acetylcysteine (NAC) on the regeneration of spinal cord injuries in rats.
Material and Methods. A total of 20 male Wistar C rats were subjected to SCI and divided into control and experimental groups. In the control group (n = 10) trepanation and SCI by means of a pressure impactor was performed without any therapy. In the study group (n = 10), 1 dose of NAC was applied intraperitoneally (150 mg/kg b.w.) immediately after SCI, and another one after 24 h. The functional outcome on the Basso-Beattie-Bresnahan (BBB) scale and sciatic functional index (SFI) and morphological features of regeneration were analyzed during a 12-week follow-up. The spinal cords and brains were collected 12 weeks after SCI for histopathological and immunohistochemical analyses.
Results. The rats treated with NAC presented some improvement in locomotor activity and spinal cord morphology when compared to the control group. Namely, the hind paw angle of rotation was significantly lower in the NAC group than in the control group. No differences were observed between the control and study groups in terms of interlimb coordination. The area of the main lesion was only slightly decreased in the NAC group as compared to the control group. The length of lesions in the injured spinal cord in the NAC group was diminished in comparison to the control group. The number of FG-positive cells was higher in the NAC group than in the control group.
Conclusion. The study showed that the neuroprotective activity of NAC had limited positive influence on the regeneration of the isolated SCI in rats.

Key words

neuroprotection, N-acetylcysteine, spinal cord injury, neuroregeneration

References (30)

  1. Cripps RA, Lee BB, Wing P, Weerts E, Mackay J, Brown D. A global map for traumatic spinal cord injury epidemiology: Towards a living data repository for injury prevention. Spinal Cord. 2011;49:493–501.
  2. Hulsebosch CE. Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ. 2002;26:238–255.
  3. Demppoulos HB, Flamm ES, Seligman ML, Pietronigro DD, Tomasula J, DeCrescito V. Further studies on free-radical pathology in the major central nervous system disorders: Effect of very high doses of methylprednisolone on the functional outcome, morphology and chemistry of experimental spinal cord impact injury. Can J Physiol Pharmacol. 1982;60:1415–1424.
  4. Sekhon LH, Fehlings MG. Epidemiology, demographics and pathophysiology of acute spinal cord injury. Spine. 2001;26 (Suppl 24):2–12.
  5. Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D. Antioxidant therapy in acute central nervous system injury: Current state. Pharmacol Rev. 2002;54:271–284.
  6. Leker RR, Shohami E. Cerebral ischemia and trauma – Different etiologies yet similar mechanisms: Neuroprotective opportunities. Brain Res Rev. 2002;39:55–73.
  7. Panickar KS, Jayakumar AR, Norenberg MD. Differential response of neural cells to trauma-induced free radical production in vitro. Neurochem Res. 2002;27:161–166.
  8. Hall ED. Antioxidant therapies for acute spinal cord injury. Neurotherapeutics. 2011;8:152–167.
  9. Rabchevsky AG, Patel SP, Springer JE. Pharmacological interventions for spinal cord injury: Where do we stand? How might we step forward? Pharmacol Ther. 2011;132:15–29.
  10. Cuzzocrea S, Mazzon E, Constantino G, Serraino I, De Sarro A, Caputi AP. Effect of N-acetylcysteine in a rat model of ischemia and reperfusion injury. Cardiovasc Res. 2000;47:537–548.
  11. Kersick C, Willoughby D. The antioxidant role of glutathione and N-acetylcysteine supplements and exercise-induced oxidative stress. J Int Soc Sports Nutr. 2005;2:38–44.
  12. Supriti S, Nakul PT, Denise DM, Abhay V, Swapan KR, Naren LB. Neuroprotective drugs in traumatic CNS injury. Open Drug Discov J. 2010;2:174–180.
  13. Gilgun-Sherky Y, Knuckey NW, Palm D, Primiano M, Epstein MH, Johanson CE. N-acetylcysteine enhances hippocampal neuronal survival after transient forebrainischemia in rats. Stroke. 1995;26:305–310.
  14. Naziroglu M, Senol M, Ghazizadeh V, Yuruker V. Neuroprotection induced by N-acetylcysteine and selenium against traumatic brain injury-induced apoptosis and calcium entry in hippocampus of rat. Cell Moll Neurobiol. 2014;34:895–903.
  15. Marcol W, Ślusarczyk W, Gzik M, et al. Air gun impactor: A novel model of graded white matter spinal cord injury in rodents. J Reconstr Microsurg. 2012;28:561–568.
  16. Basso DM, Beattie SM, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of Neurotrauma. 1995;12:1–21.
  17. Coumans JV, Lin TT, Dai HN, et al. Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neutrophins. J Neurosci. 2001;21:9334–9344.
  18. Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N-acetylcysteine for antioxidant therapy: Pharmacology and clinical utility. Expert Opin Biol Ther. 2008;8:1955–1962.
  19. Galley HF, Howdle PD, Walker BE. The effect of intravenous antioxidants in patients with septic shock. Free Radic Biol Med. 1997;23:768–774.
  20. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Morshead CM, Fehlings MG. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci. 2006;26:3377–3389.
  21. Hanci V, Kerimoğlu A, Koca K, Başkesen A, Kiliç K, Taştekin D. The biochemical effectiveness of N-acetylcysteine in experimental spinal cord injury in rats. Ulus Travma Acil Cerrahi Derg. 2010;16(1):15–21.
  22. Karalija A, Novikowa LN, Kongham PJ, Wiberg M, Novikov LN. Neuroprotective effects of N-acetylcysteine and acetyl-L-carnitine after spinal cord injury in adult rats. PLoS One. 2012;7:1–10.
  23. Kaynar MY, Erdinçler P, Tadayyon E, Belce A, Gümüstas K, Ciplak N. Effect of nimodipine and N-acetylcysteine on lipid peroxidation after experimental spinal cord injury. Neurosurg Rev. 1998;21:260–264.
  24. Khan M, Sekhon B, Jatana M, et al. Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res. 2004;76:519–527.
  25. Thomale UW, Griebenow M, Kroppenstendt SN, Unterberg AW, Stover JF. The antioxidant effect of N-acetylcysteine on experimental contusion in rats. Acta Neurochir Suppl. 2005;95:429–431.
  26. Cakir O, Erdem K, Oruc A, Kilinc N, Eren N. Neuroprotective effect of N-acetylcysteine and hypothermia on the spinal cord ischemia-reperfusion injury in animal model. Cardiovasc Surg. 2003;11:375–379.
  27. Hicdonmez T, Kanter M, Tiryaki M, Parsak T, Cobanoglu S. Neuroprotective effects of N-acetylcysteine on experimental closed head trauma in rats. Neurochem Res. 2006;31:473–481.
  28. Thomale UW, Griebenow M, Kroppenstedt SN, Unterberg AW, Stover JF. The effect of N-acetylcysteine on posttraumatic changes after controlled cortical impact in rats. Intensive Care Med. 2006;32:149–155.
  29. Cuzzocrea S, Mazzon E, Constantino G, et al. Beneficial effects of N-acetylcysteine on ischemic brain injury. Br J Pharmacol. 2000;130:1219–1226.
  30. Shahripour RB, Harrigan MR, Andrei V, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: Mechanisms of action and therapeutic opportunities. Brain and Behavior. 2014;4:108–112.