Neuroscience and Behavioral Physiology

, Volume 45, Issue 7, pp 820–828 | Cite as

Assessment of the Efficacy of Nucleotide Therapy after Sciatic Nerve Injury

  • V. A. Chavushyan
  • L. R. Gevorgyan
  • K. V. Simonyan
Article

Experimental and clinical data provide evidence of an increased need for pyrimidine nucleotides after peripheral nerve injury. The aim of the present work was to evaluate the neuroprotective efficacy of the agent Nucleo CMP (Ferrer International, which contains the nucleotides cytidine monophosphate and uridine triphosphate), after unilateral crushing of the sciatic nerve in rats. Extracellular spike activity was recorded from individual spinal cord motoneurons on the side ipsilateral to the injury using high-frequency stimulation of the distal branches (tibial nerve, common peroneal nerve) of the injured sciatic nerve. The extent and ratio of excitatory/inhibitory evoked motoneuron responses in the Nucleo CMP group approached normal. The Nucleo CMP group showed recovery of measures in the abduction reflex test and the static sciatic index of the injured limb by day 30. Single therapeutic doses of Nucleo CMP given to intact animals increased baseline and evoked spike activity of individual motoneurons from 10 to 80 min.

Keywords

sciatic nerve crushing Nucleo CMP spinal cord motoneurons 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    A. I. Orlov, Applied Statistics, Ekzamen, Moscow (2004).Google Scholar
  2. 2.
    M. Bervar, “Video analysis of standing an alternative footprint analysis to assess functional loss following injury to the rat sciatic nerve,” J. Neurosci. Meth., 102, No. 109–116 (2000).Google Scholar
  3. 3.
    A. Bozkurt, R. Deumens, J. Scheffel, et al., “Cat Walk gait analysis in assessment of functional recovery after sciatic nerve injury,” J. Neurosci. Meth., 173, 91–98 (2008).CrossRefGoogle Scholar
  4. 4.
    A. Bozkurt, J. Scheffel, G. A. Brook, et al., “Aspects of static and dynamic motor function in peripheral nerve regeneration: SSI and CatWalk gait analysis,” Behav. Brain Res., 21, No. 1, 55–62 (2011).CrossRefGoogle Scholar
  5. 5.
    A. Bozkurt, S. Tholl, S. Wehner, et al., “Evaluation of functional nerve recovery with Visual-SSI – a novel computerized approach for the assessment of the static sciatic index (SSI),” J. Neurosci. Meth., 170, 117–122 (2008).CrossRefGoogle Scholar
  6. 6.
    P. M. Bridge, D. M. Ball, S. E. Mackinnon, et al., “Nerve crush injuries – a model for axonotmesis,” Exp. Neurol., 127, No. 2, 284–290 (1994).CrossRefPubMedGoogle Scholar
  7. 7.
    G. Burnstock and G. E. Knight, “Cellular distribution and functions of P2 receptor subtypes in different systems,” Int. Rev. Cytol., 240, 31–304 (2004).CrossRefPubMedGoogle Scholar
  8. 8.
    W. W. Campbell, “Evaluation and management of peripheral nerve injury,” Clin. Neurophysiol., 119, 1951–1965 (2008).CrossRefPubMedGoogle Scholar
  9. 9.
    C. Coskun, B. Avci, B. Ocak, et al., “Effect of repeatedly given CDPcholine on cardiovascular and tissue injury in spinal shock conditions: investigation of the acute phase,” J. Pharm. Pharmacol., 62, 497–506 (2010).PubMedGoogle Scholar
  10. 10.
    J. Dijkstra, “Methods to evaluate functional nerve recovery in adult rats: walking track analysis, video analysis and the withdrawal refl ex,” J. Neurosci. Meth., 96, 89–96 (2000).CrossRefGoogle Scholar
  11. 11.
    H. U. Gerbershaden, “Pharmakotherapie im Bereich des peripheren Nervensystem,” TW Neurologie/Psyhiatrie, No. 6, 21–23 (1992).Google Scholar
  12. 12.
    P. A. Guertin, “Central pattern generator for locomotion: anatomical physiological and pathophysiological considerations,” Front. Neurol., No. 3, 183 (2013).Google Scholar
  13. 13.
    P. A. Guertin and I. Steuer, “Key central pattern generators of the spinal cord,” J. Neurosci. Res., 87, 2399–2405 (2009).CrossRefPubMedGoogle Scholar
  14. 14.
    R. M. Harris-Warrick, “Neuromodulation and fl exibility in central pattern generator networks,” Curr. Opin. Neurobiol., 21, 685–692 (2011).PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    S. Holguin, J. Martinez, C. Chow, and R. Wurtman, “Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils,” FASEB J., 22, No. 11, 3938–3946 (2008).PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    X.-E. Hou and A. Dahlström, “Synaptic vesicle proteins and neuronal plasticity in adrenergic neurons,” Neurochem. Res., 25, 1275– 1300 (2000).CrossRefPubMedGoogle Scholar
  17. 17.
    V. Jankowsk, M. Van Der Giet, H. Mischak, et al., “Dinucleoside polyphosphates: strong endogenous agonists of the purinergic system,” Brit. J. Pharmacol., 157, 1142–1153 (2009).CrossRefGoogle Scholar
  18. 18.
    A. L. Luis, S. Amado, S. Geuna, et al., “Long-term functional and morphological assessment of a standardized rat sciatic nerve crush injury with a non-serrated clamp,” Neurosci. Meth., 163, 92–104 (2007).CrossRefGoogle Scholar
  19. 19.
    C. H. Ma, T. Omura, E. J. Cobos, et al., “Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice,” Clin. Invest., 121, No. 11, 4332–4347 (2011).CrossRefGoogle Scholar
  20. 20.
    E. Mantuano, K. Henry, T. Yamauchi, et al., “The unfolded protein response is a major mechanism by which LRP1 regulates Schwann cell survival after injury,” J. Neurosci., 31, No. 38, 13376–13385 (2011).PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    T. Mert, I. Gunay, and S. Polat, “Alterations in conduction characteristics of crushed peripheral nerves,” Restor. Neurol. Neurosci., 23, No. 5–6, 347–354 (2005).PubMedGoogle Scholar
  22. 22.
    E. K. Moses, C. J. Langford, and L. Austin, “Small molecular weight RNAs altered metabolism in regenerating nerve,” Biochem. Int., 5, 177–184 (1982).Google Scholar
  23. 23.
    C. Mukherjee and R. J. Lejkowitz, “Desensitization of beta-adrenergic receptors by beta-adrenergic agonists in a cell-free system: resensitization by guanosine 5’-(beta gamma-imino)triphosphate and other purine nucleotides,” Proc. Natl. Acad. Sci. USA, 73, No. 5 1494–1498 (1976).Google Scholar
  24. 24.
    S. G. Neerven, A. Bozkurt, D. M. O’Dey, et al., “Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study.” Brach. Plexus Periph. Nerve Injury, 7, 5 (2012).Google Scholar
  25. 25.
    R. Ozay, A. Bekar, H. Kocaeli, et al., “Citicoline improves functional recovery, promotes nerve regeneration, and postoperative scarring after peripheral nerve surgery in rats,” Surg. Neurol., 68, 615–622 (2007).CrossRefPubMedGoogle Scholar
  26. 26.
    G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press (2005), 5th ed.Google Scholar
  27. 27.
    F. Schuettauf, R. Rejdak, S. Thaler, et al., “Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat,” Exp. Eye Res., 83, 1128–1134 (2006).CrossRefPubMedGoogle Scholar
  28. 28.
    J. J. Secades, “Citicoline: pharmacological and clinical review 2010 update,” Rev. Neurol., 52, 1–62 (2011).Google Scholar
  29. 29.
    G. Sun, Z. Li, X. Wang, et al., “Modulation of MAPK and Akt signaling pathways in proximal segment of injured sciatic nerves,” Neurosci. Lett., 534, 205–210 (2013).CrossRefPubMedGoogle Scholar
  30. 30.
    A. Turkkan, T. Alkan, B. Goren, et al., “Citicoline and postconditioning provides neuroprotection in a rat model of ischemic spinal cord injury,” Acta Neurochir. Wien, 152, 1033–1042 (2010).CrossRefPubMedGoogle Scholar
  31. 31.
    B. Wattig, F. Heydenreich, and G. Schalow, “Nucleotide beschleunigen die Nerven regeneration,” Z. Klin. Med., 46, 1371–1373 (1991).Google Scholar
  32. 32.
    T. Yamazaki, H. Sabit, Y. Oya, et al., “Activation of MAP kinases Akt and PDGF receptors in injured peripheral nerves,” Peripher. Nerv. Syst., 14, No. 3, 165–176 (2009).CrossRefGoogle Scholar
  33. 33.
    A. Yousuf, F. Klinger, K. Schicker, and S. Boehm, “Nucleotides control the excitability of sensory neurons via two P2Y receptors and a bifurcated signaling cascade,” Pain, 15, No. 8, 1899–1908 (2011).Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • V. A. Chavushyan
    • 1
  • L. R. Gevorgyan
    • 1
  • K. V. Simonyan
    • 1
  1. 1.Orbeli Institute of PhysiologyNational Academy of Sciences of the Republic of ArmeniaErevanArmenia

Personalised recommendations