COMBINED ACTION OF VEGETABLE POLYPHENOLS AND MESENCHYMAL STEM CELLS ON ISCHEMIC DAMAGE OF THE BRAIN
DOI:
https://doi.org/10.26577/eb.2021.v86.i1.014Abstract
The aim of the work was to evaluate the effectiveness of combined therapy of the extract of polyphenols isolated from the roots of Limonium Gmelinii and mesenchymal stem cells (MSCs) under conditions of experimentally induced ischemic brain damage in vivo. The object of this study were outbred male Wistar rats weighing 280-300 g. To create a model of focal ischemic stroke, occlusion of the middle cerebral artery (MCAO) was performed. Animals of the experimental groups received Kermek of Gmelin intragastrically; MSC transplantation was carried out by injection through the common femoral vein. Intravital assessment of the survival and distribution of transplanted MSCs was carried out using a micro CT IVIS Spectrum apparatus. Analysis of the sensorimotor functions of animals was performed using the test " Beam walk." The results of the study showed that transplanted MSCs are localized in the brain only in animals with MCAO, however, their localization in the thoracic and abdominal region was noted both in animals with and without stroke. Evaluation of sensorimotor activity showed that in animals that received MSC transplantation, partial restoration of motor functions occurred, and with combined therapy with Limonium Gmelinii extract and MSC on day 14, the motor activity of rats was restored almost to the control values. Thus, combined therapy with Limonium Gmelinii extract and mesenchymal stem cells is a more effective approach as compared to MSC monotherapy.
Key words: ischemic stroke, Limonium Gmelinii, plant polyphenols, mesenchymal stem cells.
References
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2. OECD. Health at a Glance (2011): OECD Publishing.
3. Smith H.K., Gavins F.N. (2012) The potential of stem cell therapy for stroke: is PISCES the sign? FASEB J., vol. 26, № 6, pp. 2239-2252.
4. Lees K.R., Bluhmki E., von Kummer R., Brott T.G., Toni D., Grotta J.C., Albers G.W., Kaste M., Marler J.R., Hamilton S.A., Tilley B.C., Davis S.M., Donnan G.A., Hacke W., Allen K., Mau J., Meier D., del Zoppo G., De Silva D.A., Butcher K.S., Parsons M.W., Barber P.A., Levi C., Bladin C., Byrnes G. (2010) Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet, vol. 375, № 972, pp. 1695-1703.
5. Sandercock P., Wardlaw J.M., Lindley R.I., Dennis M., Cohen G., Murray G., Innes K., Venables G., Czlonkowska A., Kobayashi A., Ricci S., Murray V., Berge E., Slot K.B., Hankey G.J., Correia M., Peeters A., Matz K., Lyrer P., Gubitz G., Phillips S.J., Arauz A. (2012) The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet, vol. 379, № 9834, pp. 2352-2363.
6. van Velthoven C.T., van de Looij Y., Kavelaars A., Zijlstra J., van Bel F., Huppi P.S., Sizonenko S., Heijnen C.J. (2012) Mesenchymal stem cells restore cortical rewiring after neonatal ischemia in mice. Annals of neurology, vol. 71, № 6, pp. 785-796.
7. Carroll J. (2012) Human cord blood for the hypoxic-ischemic neonate. Pediatric research, vol. 71, № 4 Pt 2, pp. 459-463.
8. Silvestre J.S. (2012) Pro-angiogenic cell-based therapy for the treatment of ischemic cardiovascular diseases. Thrombosis research, vol. 130 Suppl 1, pp. S90-94.
9. Булгин Д.В., Андреева О.В. (2015) Tерапевтический ангиогенез с использованием факторов роста и клеток костного мозга: биологические основы и перспективы клинического применения. Вестник трансплантологии и искусственных органов, том 17, № 3.
10. Leu S., Lin Y.C., Yuen C.M., Yen C.H., Kao Y.H., Sun C.K., Yip H.K. (2010) Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats. Journal of translational medicine, vol. 8, pp. 63.
11. Shen L.H., Li Y., Chen J., Zacharek A., Gao Q., Kapke A., Lu M., Raginski K., Vanguri P., Smith A., Chopp M. (2007) Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 27, № 1, pp. 6-13.
12. Matsuo Y., Onodera H., Shiga Y., Shozuhara H., Ninomiya M., Kihara T., Tamatani T., Miyasaka M., Kogure K. (1994) Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat. Brain research, vol. 656, № 2, pp. 344-352.
13. Зозуля Ю.А., Барабой. В.А., Сутковой Д.А. (2000) Свободнорадикальное окисление и антиоксидантная защита при патологии головного мозга. М.: Знание-М., pp. 344.
14. Ross J.A., Kasum C.M. (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annual review of nutrition, vol. 22, pp. 19-34.
15. Ferriola P.C., Cody V., Middleton E., Jr. (1989) Protein kinase C inhibition by plant flavonoids. Kinetic mechanisms and structure-activity relationships. Biochem Pharmacol., vol. 38, № 10, pp. 1617-1624.
16. Glossmann H., Presek P., Eigenbrodt E. (1981) Quercetin inhibits tyrosine phosphorylation by the cyclic nucleotide-independent, transforming protein kinase, pp60src. Naunyn Schmiedebergs Arch Pharmacol., vol. 317, № 1, pp. 100-102.
17. Lyubchenko T.A., Wurth G.A., Zweifach A. (2003) The actin cytoskeleton and cytotoxic T lymphocytes: evidence for multiple roles that could affect granule exocytosis-dependent target cell killing. J Physiol., vol. 547, № Pt 3, pp. 835-847.
18. Ratty A.K., Das N.P. (1988) Effects of flavonoids on nonenzymatic lipid peroxidation: structure-activity relationship. Biochem Med Metab Biol., vol. 39, № 1, pp. 69-79.
19. Schwartz L.B. (1987) Mediators of human mast cells and human mast cell subsets. Ann Allergy., vol. 58, № 4, pp. 226-235.
20. Chuang D.Y., Chan M.H., Zong Y., Sheng W., He Y., Jiang J.H., Simonyi A., Gu Z., Fritsche K.L., Cui J., Lee J.C., Folk W.R., Lubahn D.B., Sun A.Y., Sun G.Y. (2013) Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells. J Neuroinflammation, vol. 10, pp. 15.
21. Simonyi A., Wang Q., Miller R.L., Yusof M., Shelat P.B., Sun A.Y., Sun G.Y. (2005) Polyphenols in cerebral ischemia: novel targets for neuroprotection. Molecular neurobiology, vol. 31, № 1-3, pp. 135-147.
22. Panickar K.S., Jang S. (2013) Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia. Recent patents on food, nutrition & agriculture, vol. 5, № 2, pp. 128-143.
23. Tsoy A., Zhussupova G., Shayakhmetov Y., Umbayev B., Askarova S. (2016) POTENTIAL OF PLANT EXTRACT FROM LIMONIUM GMELINII FOR STROKE THERAPY. INTERNATIONAL JOURNAL OF STROKE, vol. 11, № SUPP 3, pp. 257-257.
24. Zhang L., Chan C. (2010) Isolation and enrichment of rat mesenchymal stem cells (MSCs) and separation of single-colony derived MSCs. J Vis Exp., № 37, e1852.
25. Munoz-Elias G., Marcus A.J., Coyne T.M., Woodbury D., Black I.B. (2004) Adult bone marrow stromal cells in the embryonic brain: engraftment, migration, differentiation, and long-term survival. The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 24, № 19, pp. 4585-4595.
26. Uluc K., Miranpuri A., Kujoth G.C., Akture E., Baskaya M.K. (2011) Focal cerebral ischemia model by endovascular suture occlusion of the middle cerebral artery in the rat. Journal of visualized experiments : JoVE, № 48:1978.
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Nurkenov Т. Т., Tsoy А. К., Zhusupova G. Е., Olzhayev, F. S., Ogay, V. Y., Umbayev, B. A., Shalakhmetova Т. М., & Askarova, S. N. (2021). COMBINED ACTION OF VEGETABLE POLYPHENOLS AND MESENCHYMAL STEM CELLS ON ISCHEMIC DAMAGE OF THE BRAIN. Experimental Biology, 86(1), 146–156. https://doi.org/10.26577/eb.2021.v86.i1.014
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HUMAN and ANIMAL PHYSIOLOGY
