Abstract

Over the past couple of decades there have been no major improvements in the treatment of either acute ischaemic stroke or one of its major complications, neurodegenerative dementia. The majority of promising clinical trials associated with attempts to protect against the debilitating effects of Alzheimer's disease have ended prematurely following exasperation of the condition. Citicoline has been used extensively in patient trials following stroke but strong evidence for its ability to enhance neuroprotection and improve recovery are still lacking. Following our demonstration that this molecule can also enhance angiogenesis/vascularization we hypothesized that it could benefit patients suffering from vascular dementia. Here we describe our recent findings, discuss citicoline signalling and possible links to neurovascular degradation/protection, and consider novel mathematical-biological systems methodology for the identification of potential protective/therapeutic agents against this disease.

Keywords: CDP-Choline Neuroprotection · Vascular Remodeling · Vascular Dementia

References

  1. 1.Rapp P.E. An atlas of cellular oscillators, J. Exp. Biology 1979; 81: 281-306. New Model of Neurodegeneration, Raid Al-Baradie et al.
  2. 2.Hierlemann A., Frey U., Hafizovic S., Heer F. Growing cells atop microelectronic chips: Interfacing electrogenic cells in vitro with CMOS-based microelectrode arrays introduction, Proc. of IEEE 2011; 99: 249251.
  3. 3.Kruse K. and Jülicher F. Oscillations in cell biology, Opinion in Cell Biology 2005; 17: 20–26.
  4. 4.Hodgkin A. and Huxley A. A quantitative description of membrane current and its application to conduction and excitation in nerve, J. Physiol. 1952; 117: 500-544.
  5. 5.Borresen J. and Lynch S. Neuronal computers, Nonlinear Anal. Theory, Meth. & Appl. 2009; 71:2372-2376.
  6. 6.Lynch S. and Borresen J. Binary half adder using oscillators, International Publication Number WO 2012/001372 A1, 1-57.
  7. 7.Lynch S. and Borresen J. Binary half-adder and other logic circuits, UK Patent Number 2012; GB 2481717 A, 1-57.
  8. 8.James CD, Davis R., Meyer M. Aligned microcontact printing of micrometer-scale poly-L-lysine structures for controlled growth of cultured neurons on planar microelectrode arrays, IEEE Trans. on Biomedical Engineering 2000; 47: 17-21.
  9. 9.Delivopoulos E, Murray AF, MacLeod N.K. and Curtis JC. Guided growth of neurons and glia using microfabricated patterns of parylene-C on a silicon dioxide background, Biomaterials 2009; 30: 20482058.
  10. 10.Xu F.L., Fakas S., Korbeek S. et al. Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-DAspartate receptors, Molecular Brain (2012); 5: 1-14.
  11. 11.Fromherz P., Eick S. and Hofmann B. Neuroelectronic Interfacing with Semiconductor Chips, Nanoelectronics and Infromation Technology, Ed. R Waser, 2nd Edition. 2012.
  12. 12.Stephens C.L., Toda H., Palmer T.D. Adult neural progenitor cells reactivate superbursting in mature neural networks, Experimental Neurology 2012; 234: 20-30.
  13. 13.Arthur J.V., Merolla P.A., Akopyan F. Building block of a programmable neuromorphic substrate: A digital neurosynaptic core, International Joint Conference on Neural Networks 2012. 9 ORIGINAL ARTICLE
  14. 14.Jiang HB., Ren Y., Yuen EY. Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells, Nature Communications 2012; 3: Article number
  15. 15.Krupinski J., Abudawood M., Matou-Nasri S. Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1, Vascular Cell 2012; 4:
  16. 16.Borresen J. and Lynch S. Oscillatory threshold logic, PLoS ONE 2012; 7: e48498.
  17. 17.Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, Arnold SE. Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline.J Clin Invest. 2012 Apr 2;122(4):1316-38. doi: 10.1172/JCI59903. doi:10.1172/JCI59903
  18. 18.O'Neill C, Kiely AP, Coakley MF, Manning S, Long-Smith CM Insulin and IGF-1 signalling: longevity, protein homoeostasis and Alzheimer's disease.Biochem Soc Trans. 2012 Aug ;40(4):721-7. doi: 10.1042/BST20120080. doi:10.1042/BST20120080
  19. 19.Krupinski J, Abudawood M, Matou-Nasri S, Al-Baradie R, Petcu E, Justicia C, Planas A, Liu D, Rovira N, Grau-Slevin M, New Model of Neurodegeneration, Raid Al-Baradie et al. MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1 Secades J, Slevin M.Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1.Vasc Cell. 2012 Dec 10;4(1):20. [Epub ahead of print]
  20. 20.Biron KE, Dickstein DL, Gopaul R, Jefferies WAPLoS One. 2011;6(8):e23789. doi: 10.1371/journal.pone.0023789. Epub 2011 Aug 31.Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer's disease. doi:10.1371/journal.pone.0023789
  21. 21.Grammas P, Sanchez A, Tripathy D, Luo E, Martinez J. Vascular signaling abnormalities in Alzheimer disease.Cleve Clin J Med. 2011 Aug;78 Suppl 1:S50-3. doi: 10.3949/ccjm.78.s1.09. doi:10.3949/ccjm.78.s1.09
  22. 22.Jantaratnotai N, Ryu JK, Schwab C, McGeer PL, McLarnon JG.Comparison of Vascular Perturbations in an Aβ-Injected Animal Model and in AD Brain. Int J Alzheimers Dis. 2011;2011:918280. doi: 10.4061/2011/918280. Epub 2011 Sep 29. doi:10.4061/2011/918280
  23. 23.Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM.Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin.J Neurosci. 2009 Jul 15;29(28) :9078-89. doi: 10.1523/JNEUROSCI.107109.2009. 10 doi:10.1523/JNEUROSCI.107109.2009
Majmaah Journal of Health Sciences · eISSN 1658-8223 · Majmaah University · open access