Neuroscience and Behavioral Physiology

, Volume 43, Issue 6, pp 706–711 | Cite as

Neuroprotective Therapy with Citicoline (Ceraxon) in Patients with Ischemic Stroke

  • M. Yu. MartynovEmail author
  • A. N. Boiko
  • P. R. Kamchatnov
  • A. A. Kabanov
  • A. N. Yasamanova
  • I. A. Shchukin
  • T. I. Kolesnikova
  • V. I. Chubykin
  • A. P. Glukhareva
  • E. I. Gusev

The dynamics of neurological symptoms were assessed using the Scandinavia Stroke Scale and functional disease outcomes with the Barthel index and modified Rankin scale in 89 patients during the acute period of ischemic stroke of moderate severity, whose treatment included citicoline (Ceraxon) i.v. and p.o. The results were compared with those from a reference group (52 patients) selected in terms of clinical and demographic parameters, who received similar treatment without citicoline. By discharge from hospital (days 21–24 of illness), there was significantly (p < 0.05) greater recovery in the study group. The efficacy of citicoline was significantly (p < 0.05) greater in patients aged less than 70 years and when citicoline was given in the first hours of illness.


ischemic stroke cytoprotective therapy citicoline 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    E. I. Gusev, V. I. Skvortsova, and L. V. Stakhovskaya, “The problem of stroke in the Russian Federation: a time for positive actions,” Zh. Nevrol. Psikhiat., 107, No. 6, 4–10 (2007).Google Scholar
  2. 2.
    P. A. Lapchak, “Emerging therapies: pleiotropic multi-target drugs to treat stroke victims,” Transl. Stroke Res., 2, 129–135 (2011).PubMedCrossRefGoogle Scholar
  3. 3.
    M. D. Ginsberg, “Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection: The 2002 Thomas Willis Lecture,” Stroke, 34, 214–223 (2003).PubMedCrossRefGoogle Scholar
  4. 4.
    E. I. Gusev, A. N. Boiko, V. L. Baratashvili, et al., “Results obtained using citicoline (Ceraxon) in patients with acute cerebral stroke,” Med. Krit. Sostoyanii, 2, 42–47 (2010).Google Scholar
  5. 5.
    A. Rogalewski, A. Schneider, B. E. Ringelstein, and W. R. Schabitz, “Toward a multimodal neuroprotective treatment of stroke,” Stroke, 37, 1129–1136 (2006).PubMedCrossRefGoogle Scholar
  6. 6.
    A. A. Mangoni and S. H. Jackson, “Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications,” Brit. J. Clin. Pharmacol., 57, No. 1, 6–14 (2004).CrossRefGoogle Scholar
  7. 7.
    G. Trifiró and E. Spina, “Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems,” Curr. Drug. Metab., 12, No. 4, 542–549 (2011).Google Scholar
  8. 8.
    X. Bao, P. J. Mills, B. K. Rana, et al., “Interactive effects of common β2-adrenoceptor haplotypes and age on susceptibility to hypertension and receptor function,” Hypertension, 46, 301–307 (2005).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Meller, S. Jakobsen, and A. Gjedde, “Parametric and regional maps of free serotonin 5-HT1A receptor sites in human brain as function of age in healthy humans,” Neuropsychopharmacology, 32, 1707–1714 (2007).CrossRefGoogle Scholar
  10. 10.
    R. M. Adibhatla, J. F. Hatcher, E. C. Larsen, et al., “CDP-choline significantly restores phosphatidylcholine levels by differentially affecting phospholipase A2 and CTP:phosphocholine cytidyltransferase after stroke,” J. Biol. Chem., 281, No. 10, 6718–6725 (2005).PubMedCrossRefGoogle Scholar
  11. 11.
    A. Farooqui, L. Horrocks, and T. Farooqui, “Glycerophospholipids in brain: their metabolism, incorporation to membranes, functions, and involvement in neurological disorders,” Chem. Phys. Lipids, 106, 1–29 (2000).PubMedCrossRefGoogle Scholar
  12. 12.
    Z. Li and D. E. Vance, “Phosphatidylcholine and choline homeostasis,” J. Lipid Res., 49, 1187–1194 (2008).PubMedCrossRefGoogle Scholar
  13. 13.
    O. Hurtado, M. A. Moro, A. Cárdenas, et al., “Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport,” Neurobiol. Dis., 18, 336–345 (2005).PubMedCrossRefGoogle Scholar
  14. 14.
    M. Martinet, P. Fonlupt, and H. Pacheco, “Effects of cytidine 5'-diphosphocholine on norepinephrine, dopamine and serotonin synthesis in various regions of the rat brain,” Arch. Int. Pharmacodyn. Ther., 239, 52–61 (1979).PubMedGoogle Scholar
  15. 15.
    M. Alonso de Laciñana, M. Gutiérrez, J. M. Rada, et al., “Effect of combined therapy with thrombolysis and citicoline in a rat model of embolic stroke,” J. Neurol. Sci., 247, 121–129 (2006).CrossRefGoogle Scholar
  16. 16.
    O. Hurtado, A. Cardenas, J. M. Pradillo, et al., “A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke,” Neurobiol. Dis., 26, 105–111 (2007).PubMedCrossRefGoogle Scholar
  17. 17.
    J. Alvarez-Sabín and G. C. Román, “Citicoline in vascular cognitive impairment and vascular dementia after stroke,” Stroke, 42, Suppl., 40–43 (2011).CrossRefGoogle Scholar
  18. 18.
    R. A. Cohen, J. N. Browndyke, D. J. Moser, et al., “Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes,” Cerebrovasc. Dis., 16, 199–204 (2003).PubMedCrossRefGoogle Scholar
  19. 19.
    M. M. Odinak and I. A. Voznyuk, “The role of exogenous choline in protection and recovery of brain matter in stroke. Quality of life,” Meditsina, 21, No. 4, 1–7 (2007).Google Scholar
  20. 20.
    W. M. Clark, S. J. Warach, L. C. Pettigrew, et al., “A randomized dose–response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group,” Neurology, 49, 671–678 (1997).PubMedCrossRefGoogle Scholar
  21. 21.
    A. Davalos, J. Castillo, J. Alvarez-Sabin, et al., “Oral citicoline in acute ischemic stroke: An individual patient data pooling analysis of clinical trials,” Stroke, 33, No. 12, 2850–2857 (2002).PubMedCrossRefGoogle Scholar
  22. 22.
    S. Warach, L. C. Pettigrew, J. F. Dashe, et al., “Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging,” Citicoline 010 investigators,” Ann. Neurol., 48, No. 5, 713–722 (2000).PubMedCrossRefGoogle Scholar
  23. 23.
    M. F. Kuo, J. Grosch, E. Fregni, et al., “Focusing effect of acetylcholine on neuroplasticity in the human motor cortex,” J. Neurosci., 27, No. 52, 14442–14447 (2007).PubMedCrossRefGoogle Scholar
  24. 24.
    F. Meintzschel and U. Ziemann, “Modification of practice-dependent plasticity in human motor cortex by neuromodulators,” Cerebral Cortex, 16, 1106–1115 (2006).PubMedCrossRefGoogle Scholar
  25. 25.
    M. M. Silveri, J. Dikan, A. J. Ross, et al., “Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy,” NMR Biomed., 21, 1066–1075 (2008).PubMedCrossRefGoogle Scholar
  26. 26.
    V. Rema, K. K. Bali, R. Ramachandra, et al., “Cytidine-5-diphosphocholine supplement early in life induces stable increase in dendritic complexity of neurons in the somatosensory cortex of adult rats,” Neurosci., 155, No. 2, 556–564 (2008).CrossRefGoogle Scholar
  27. 27.
    V. Bramanti, D. Bronzi, D. Tomassoni, et al., “Effect of choline-containing phospholipids on transglutaminase activity in primary astroglial cell cultures,” Clin. Exp. Hypertens., 30, No. 8, 798–807 (2008).PubMedCrossRefGoogle Scholar
  28. 28.
    I. D. Grachev and A. V. Apkarian, “Aging alters regional multichemical profile of the human brain: an in vivo 1H-MRS study of young versus middle-aged subjects,” J. Neurochem., 76, 582–593 (2001).PubMedCrossRefGoogle Scholar
  29. 29.
    K. Haga, Y. Khor, A. Farrall, and J. M. Wardlaw, “A systematic review of brain metabolite changes, measured with 1H magnetic resonance spectroscopy, in healthy aging,” Neurobiol. Aging, 30, 353–363 (2009).PubMedCrossRefGoogle Scholar
  30. 30.
    M. Castellanos, T. Sobrino, and J. Castillo, “Evolving paradigms for neuroprotection: molecular identification of ischemic penumbra,” Cerebrovasc. Dis., 21, No. 2, 71–79 (2006).PubMedCrossRefGoogle Scholar
  31. 31.
    T. J. Quinn, P. Langhorne, and D. J. Stott, “Barthel index for stroke trials: development, properties, and application,” Stroke, 42, 1146–1151 (2011).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • M. Yu. Martynov
    • 1
    Email author
  • A. N. Boiko
    • 1
  • P. R. Kamchatnov
    • 1
  • A. A. Kabanov
    • 1
  • A. N. Yasamanova
    • 1
  • I. A. Shchukin
    • 1
  • T. I. Kolesnikova
    • 1
  • V. I. Chubykin
    • 1
  • A. P. Glukhareva
    • 1
  • E. I. Gusev
    • 1
  1. 1.Department of Neurology and NeurosurgeryN. I. Pirogov Russian National Research Medical UniversityMoscowRussia

Personalised recommendations