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Blood Plasma Trophic Growth Factors Predict the Outcome in Patients with Acute Ischemic Stroke

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Bioinformatics and Biomedical Engineering (IWBBIO 2020)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 12108))

Abstract

Stroke is an acute disorder of CNS being the leading factor of mortality and disability of the population. Dynamic assessment of trophic growth factors expression is a promising tool to predict the outcome of ischemic stroke. We investigated the concentration dynamics of the brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in blood plasma of patients with acute ischemic stroke. 56 patients took part in the study. Venous blood was collected from all patients on the first, 7th and 21st day of their hospital stay. BDNF and VEGF plasma concentrations were measured using ELISA. Our study shows, that not single, but serial dynamic measures of BDNF plasma concentrations in the acute period of ischemic stroke have a prognostic significance. Increasing of the BDNF plasma concentration on day 7 in comparison to the concentration on day 1 was significantly associated with a better clinical outcome of acute ischemic stroke. Extremely high VEGF plasma concentrations (more than 260 pg/mL) on days 1 and 7 from the ischemic stroke onset were significantly associated with a worse clinical outcome on day 21 and a less favorable rehabilitation prognosis. Serial measurement of plasma concentrations of trophic growth factors in patients with ischemic stroke presents a rather simple, reliable and minimally invasive method of dynamic assessment of the clinical course of acute ischemic stroke and early outcome prediction.

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References

  1. Kim, G., Kim, E.: The effects of antecedent exercise on motor function recovery and brain-derived neurotrophic factor expression after focal cerebral ischemia in rats. J. Phys. Ther. Sci. 25(5), 553–556 (2013)

    Article  Google Scholar 

  2. Skvortsova, V., Evzelman, M.: Ischemic stroke, p. 404 (2006). (in Russian)

    Google Scholar 

  3. Emanueli, C., Schratzberger, P., Kirchmair, R., Madeddu, P.: Paracrine control of vascularization and neurogenesis by neurotrophins. Br. J. Pharmacol. 140(4), 614–619 (2003)

    Article  CAS  Google Scholar 

  4. Huang, E.J., Reichardt, L.F.: Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci. 24(1), 677–736 (2001)

    Article  CAS  Google Scholar 

  5. Roux, P.P., Barker, P.A.: Neurotrophin signaling through the p75 neurotrophin receptor. Prog. Neurobiol. 67(3), 203–233 (2002)

    Article  CAS  Google Scholar 

  6. Casoli, T., Giuli, C., Balietti, M., Giorgetti, B., Solazzi, M., Fattoretti, P.: Effect of cognitive training on the expression of brain-derived neurotrophic factor in lymphocytes of mild cognitive impairment patients. Rejuvenation Res. 17(2), 235–238 (2014)

    Article  CAS  Google Scholar 

  7. Sartorius, A., et al.: Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry 42(06), 270–276 (2009)

    Article  CAS  Google Scholar 

  8. Gottlieb, M., Bonova, P., Danielisova, V., Nemethova, M., Burda, J., Cizkova, D.: Brain-derived neurotrophic factor blood levels in two models of transient brain ischemia in rats. Gen. Physiol. Biophys. 32, 139–142 (2013)

    Article  CAS  Google Scholar 

  9. Wang, J., et al.: Low serum levels of brain-derived neurotrophic factor were associated with poor short-term functional outcome and mortality in acute ischemic stroke. Mol. Neurobiol. 54(9), 7335–7342 (2017). https://doi.org/10.1007/s12035-016-0236-1

    Article  CAS  PubMed  Google Scholar 

  10. Rodier, M., et al.: Relevance of post-stroke circulating BDNF levels as a prognostic biomarker of stroke outcome. Impact of rt-PA treatment. PLoS ONE 10(10), e0140668 (2015)

    Article  Google Scholar 

  11. Berretta, A., Tzeng, Y.C., Clarkson, A.N.: Post-stroke recovery: the role of activity-dependent release of brain-derived neurotrophic factor. Expert. Rev. Neurother. 14(11), 1335–1344 (2014)

    Article  CAS  Google Scholar 

  12. Madinier, A., et al.: Ipsilateral versus contralateral spontaneous post-stroke neuroplastic changes: involvement of BDNF? Neuroscience 231, 169–181 (2013)

    Article  CAS  Google Scholar 

  13. Clarkson, A.N., Overman, J.J., Zhong, S., Mueller, R., Lynch, G., Carmichael, S.T.: AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke. J. Neurosci. 31(10), 3766–3775 (2011)

    Article  CAS  Google Scholar 

  14. Schäbitz, W., et al.: Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke 31(9), 2212–2216 (2000)

    Article  Google Scholar 

  15. Schäbitz, W.R., et al.: Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis. Stroke 38(7), 2165–2172 (2007)

    Article  Google Scholar 

  16. Di Lazzaro, V., et al.: BDNF plasma levels in acute stroke. Neurosci. Lett. 422(2), 128–130 (2007)

    Article  Google Scholar 

  17. Béjot, Y., Mossiat, C., Giroud, M., Prigent-Tessier, A., Marie, C.: Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies. PLoS ONE 6(12), e29405 (2011)

    Article  Google Scholar 

  18. Sun, J., Ke, Z., Yip, S.P., Hu, X.l., Zheng, X.x., Tong, K.y.: Gradually increased training intensity benefits rehabilitation outcome after stroke by BDNF upregulation and stress suppression. BioMed Res. Int. 2014, 8 (2014). https://doi.org/10.1155/2014/925762. Article ID 925762. PMCID: PMC4090448. PMID: 25045713

  19. Senger, D.R., Galli, S.J., Dvorak, A.M., Perruzzi, C.A., Harvey, V.S., Dvorak, H.F.: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219(4587), 983–985 (1983)

    Article  CAS  Google Scholar 

  20. Mărgăritescu, O., Pirici, D., Mărgăritescu, C.: VEGF expression in human brain tissue after acute ischemic stroke. Rom. J. Morphol. Embryol. 52(4), 1283–1292 (2011)

    PubMed  Google Scholar 

  21. Zhang, Z.G., et al.: VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J. Clin. Investig. 106(7), 829–838 (2000)

    Article  CAS  Google Scholar 

  22. Gerber, H.P., et al.: Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 32-kinase/Akt signal transduction pathway requirement for Flk-1/KDR activation. J. Biol. Chem. 273(46), 30336–30343 (1998)

    Article  CAS  Google Scholar 

  23. Pedram, A., Razandi, M., Levin, E.R.: Extracellular signal-regulated protein kinase/Jun kinase cross-talk underlies vascular endothelial cell growth factor-induced endothelial cell proliferation. J. Biol. Chem. 273(41), 26722–26728 (1998)

    Article  CAS  Google Scholar 

  24. Hirashima, M.: Regulation of endothelial cell differentiation and arterial specification by VEGF and Notch signaling. Anat. Sci. Int. 84(3), 95–101 (2009). https://doi.org/10.1007/s12565-009-0026-1

    Article  CAS  PubMed  Google Scholar 

  25. Sentilhes, L., et al.: Vascular endothelial growth factor and its high-affinity receptor (VEGFR-2) are highly expressed in the human forebrain and cerebellum during development. J. Neuropathol. Exp. Neurol. 69(2), 111–128 (2010)

    Article  CAS  Google Scholar 

  26. Svensson, B., et al.: Vascular endothelial growth factor protects cultured rat hippocampal neurons against hypoxic injury via an antiexcitotoxic, caspase-independent mechanism. J. Cereb. Blood Flow Metab. 22(10), 1170–1175 (2002)

    Article  CAS  Google Scholar 

  27. Yang, J., Yao, Y., Chen, T., Zhang, T.: VEGF ameliorates cognitive impairment in in vivo and in vitro ischemia via improving neuronal viability and function. Neuromolecular Med. 16(2), 376–388 (2014). https://doi.org/10.1007/s12017-013-8284-4

    Article  CAS  PubMed  Google Scholar 

  28. Zhang, R., Zhang, Z., Zhang, L., Chopp, M.: Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience 105(1), 33–41 (2001)

    Article  CAS  Google Scholar 

  29. Liu, F., Ni, J.J., Huang, J.J., Kou, Z.W., Sun, F.Y.: VEGF overexpression enhances the accumulation of phospho-S292 MeCP2 in reactive astrocytes in the adult rat striatum following cerebral ischemia. Brain Res. 1599, 32–43 (2015)

    Article  CAS  Google Scholar 

  30. Li, W.L., Fraser, J.L., Shan, P.Y., Zhu, J., Jiang, Y.J., Wei, L.: The role of VEGF/VEGFR2 signaling in peripheral stimulation-induced cerebral neurovascular regeneration after ischemic stroke in mice. Exp. Brain Res. 214(4), 503 (2011). https://doi.org/10.1007/s00221-011-2849-y

    Article  CAS  PubMed  Google Scholar 

  31. Clayton, J.A., Chalothorn, D., Faber, J.E.: Vascular endothelial growth factor-a specifies formation of native collaterals and regulates collateral growth in ischemia. Circ. Res. 103(9), 1027–1036 (2008)

    Article  CAS  Google Scholar 

  32. Cao, L., et al.: VEGF links hippocampal activity with neurogenesis, learning and memory. Nat. Genet. 36(8), 827 (2004)

    Article  CAS  Google Scholar 

  33. Sluimer, J.C., Daemen, M.J.: Novel concepts in atherogenesis: angiogenesis and hypoxia in atherosclerosis. J. Pathol. J. Pathol. Soc. Gt. Br. Irel. 218(1), 7–29 (2009)

    Google Scholar 

  34. van Bruggen, N., et al.: VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J. Clin. Investig. 104(11), 1613–1620 (1999)

    Article  Google Scholar 

  35. Li, Y.N., Pan, R., Qin, X.J., Yang, W.L., Qi, Z., Liu, W., Liu, K.J.: Ischemic neurons activate astrocytes to disrupt endothelial barrier via increasing vegf expression. J. Neurochem. 129(1), 120–129 (2014)

    Article  CAS  Google Scholar 

  36. Gunsilius, E., Petzer, A.L., Stockhammer, G., Kähler, C.M., Gastl, G.: Serial measurement of vascular endothelial growth factor and transforming growth factor-beta1 in serum of patients with acute ischemic stroke. Stroke 32(1), 275–278 (2001)

    Article  CAS  Google Scholar 

  37. Slevin, M., Krupinski, J., Slowik, A., Kumar, P., Szczudlik, A., Gaffney, J.: Serial measurement of vascular endothelial growth factor and transforming growth factor-\(\beta \)1 in serum of patients with acute ischemic stroke. Stroke 31(8), 1863–1870 (2000)

    Article  CAS  Google Scholar 

  38. Lee, S.C., Lee, K.Y., Kim, Y.J., Kim, S.H., Koh, S.H., Lee, Y.J.: Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis. Eur. J. Neurol. 17(1), 45–51 (2010)

    Article  Google Scholar 

  39. Gonchar, I., Prudyvus, I., Stepanova, J.: Expression of vascular endothelial growth factor in patients with acute ischemic stroke. Zhurnal nevrologii i psihiatrii 113(3), 25–29 (2013)

    CAS  Google Scholar 

  40. Gonchar, I., Stepanova, J.: Vascular endothelial growth factor in patients with non-cardioembolic brain infarction with mild atherosclerotic damage of cerebral arteries. Voennaya medicina 21(4), 36–39 (2011)

    Google Scholar 

  41. Adams Jr., H.P., et al.: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke 24(1), 35–41 (1993)

    Article  Google Scholar 

  42. Navarro-Sobrino, M., et al.: A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke. Atherosclerosis 216(1), 205–211 (2011)

    Article  CAS  Google Scholar 

  43. Okazaki, H., Beppu, H., Mizutani, K., Okamoto, S., Sonoda, S.: Changes in serum growth factors in stroke rehabilitation patients and their relation to hemiparesis improvement. J. Stroke Cerebrovasc. Dis. 23(6), 1703–1708 (2014)

    Article  Google Scholar 

  44. Fukunaga, K.: Introduction to Statistical Pattern Recognition. Academic Press, London (1990)

    Google Scholar 

  45. Gorban, A.N., Zinovyev, A.Y.: Fast and user-friendly non-linear principal manifold learning by method of elastic maps. In: 2015 IEEE International Conference on Data Science and Advanced Analytics, DSAA 2015, Campus des Cordeliers, Paris, France, 19–21 October 2015, pp. 1–9 (2015)

    Google Scholar 

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Acknowledgements

The work was supported by the State Assignment for Research issued by the Ministry of Public Health of the Russian Federation (2018–2020).

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Authors and Affiliations

  1. I.S. Berzon Krasnoyarsk Interregional Clinical Hospital No 20, 12 Instrumentalnaya Street, 660123, Krasnoyarsk, Russia

    Valeriia Roslavtceva & Vera Laptenkova

  2. Institute of Computational Modelling of SB RAS, Akademgorodok, 660036, Krasnoyarsk, Russia

    Evgeniy Bushmelev & Michael Sadovsky

  3. Voino-Yasenetsy Krasnoyarsk State Medical University, 1 P. Zheleznyaka Street, 660022, Krasnoyarsk, Russia

    Pavel Astanin, Tatyana Zabrodskaya, Alla Salmina, Semen Prokopenko & Michael Sadovsky

  4. Siberian Federal University, 79 Svobodny Prosp., 660041, Krasnoyarsk, Russia

    Michael Sadovsky

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  1. Valeriia Roslavtceva
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Correspondence to Valeriia Roslavtceva .

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Editors and Affiliations

  1. University of Granada, Granada, Spain

    Ignacio Rojas

  2. University of Granada, Granada, Spain

    Olga Valenzuela

  3. University of Granada, Granada, Spain

    Fernando Rojas

  4. University of Granada, Granada, Spain

    Luis Javier Herrera

  5. University of Chicago and Fundacion Progreso y Salud, Granada, Spain

    Francisco Ortuño

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Roslavtceva, V. et al. (2020). Blood Plasma Trophic Growth Factors Predict the Outcome in Patients with Acute Ischemic Stroke. In: Rojas, I., Valenzuela, O., Rojas, F., Herrera, L., Ortuño, F. (eds) Bioinformatics and Biomedical Engineering. IWBBIO 2020. Lecture Notes in Computer Science(), vol 12108. Springer, Cham. https://doi.org/10.1007/978-3-030-45385-5_3

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  • DOI: https://doi.org/10.1007/978-3-030-45385-5_3

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