Prediction of the outcome of the acute phase of ischemic stroke: the role of apoptotic markers

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Abstract

Introduction. Neuronal cell death (apoptosis) is not only a direct consequence of cerebral infarction, but also a crucial pathogenetic link of ischemic injury. Nevertheless, the role of apoptotic markers in prediction of the functional outcome of the acute phase of ischemic stroke (IS) has not been established.

Objective. To determine the possibility of predicting the outcome of the acute phase of ischemic stroke in the earliest period after its development by measuring thes FasL and sFas concentrations in peripheral blood.

Materials and methods. One hundred fifty-five individuals underwent in-hospital examination. They were subdivided into 3 groups: the control group included healthy volunteers (n=28) and two groups of patients depending on the outcome of the acute phase of IS: either with favourable (National Institutes of Health Stroke Scale score on day 21 ≤ 5) or unfavourable (the NIHSS score on day 21 > 5) outcomes. Concentrations of sFas and sFasL were measured on day 1, 7, and 21 after ischemic stroke by ELISA; the sFasL/sFas ratio was also determined.

Results. The outcome is favourable (NIHSS score on day 21 ≤ 5) if the sFasL/sFas ratio is ≤ 2.11 ± 0.58; otherwise, the outcome is unfavourable (NIHSS scoreon day 21 > 5).Conclusions. The proposed method is characterized by prognostic significance and high accuracy and can be used in clinical practice to determine the strategy for managing patients with IS.

About the authors

Svetlana P. Sergeeva

Sechenov First Moscow State Medical University

Author for correspondence.
Email: svetlanapalna@mail.ru
Russian Federation, Moscow

A. A. Savin

A.I. Yevdokimov Moscow State University of Medicine and Dentistry

Email: svetlanapalna@mail.ru
Russian Federation, Moscow

V. V. Arkhipov

Sechenov First Moscow State Medical University

Email: svetlanapalna@mail.ru
Russian Federation, Moscow

M. M. Gul’tyaev

A.I. Yevdokimov Moscow State University of Medicine and Dentistry

Email: svetlanapalna@mail.ru
Russian Federation, Moscow

I. D. Breslavich

Sechenov First Moscow State Medical University

Email: svetlanapalna@mail.ru
Russian Federation, Moscow

P. F. Litvitskii

Sechenov First Moscow State Medical University

Email: svetlanapalna@mail.ru
Russian Federation, Moscow

References

  1. Lloyd-Jones D., Adams R., Carnethon M. et al. Heart disease and strokestatistics–2009 update a report from the American Heart Association StatisticsCommittee and Stroke Statistics Subcommittee. Circulation 2009; 119(3): e21–e181. doi: 10.1161/CIRCULATIONAHA.108.191261. PMID: 19075105.
  2. Roger V.L., Go A.S., Lloyd-Jones D.M. et al. Heart disease and stroke statistics–2012 update a report from the American heart association. Circulation 2012;125(1): e2-e220. doi: 10.1161/CIR.0b013e31823ac046. PMID: 22179539.
  3. Stakhovskaya L.V., Klochikhina O.A., Bogatyreva M.D., Kovalenko V.V. [Epidemiologyof stroke in the Russian Federation: results of territory's populationregistry (2009-2010)]. Zh Nevrol Psikhiatr Im S S Korsakova. 2013; 113(5):4–10. PMID: 23739494. (In Russ).
  4. Karpova E.N., Murav'ev K.A., Murav'eva V.N. et al. [Epidemiology and riskfactors of stroke]. Sovremennye problemy nauki i obrazovaniya 2015; 4: 1–9. (InRuss).
  5. Piradov M.A., Tanashyan M.M., Domashenko M.A. et al. [Neuroprotectionin cerebrovascular diseases: is it the search for life on Mars or a promising trendof treatment? Part 1. Acute stroke]. Annaly klinicheskoy i eksperimental'noy nevrologii2015; 9 (1): 41–50. (In Russ).
  6. Stakhovskaya L.V., Shekhovtsova K.V., Rozhkova T.I. et al. [Medical serviceto patients with stroke at the prehospital stage in different cities of the RussianFederation]. Zh Nevrol Psikhiatr Im S S Korsakova. 2010; 110 (9 Pt 2): 36–41.PMID: 21462439. (In Russ).
  7. Tanashyan M.M., Raskurazhev A.A., Shabalina A.A. et al. [Biomarkers of cerebralatherosclerosis: the capabilities of early diagnosis and prognosis of individualrisk]. Annaly klinicheskoy i eksperimental'noy nevrologii 2015; 9(3): 20–25.(In Russ).
  8. Cadena S.G., Massieu L. Caspases and their role in inflammation and ischemicneuronal death. Focus on caspase-12. Apoptosis 2016; 21(7): 763–777.doi: 10.1007/s10495-016-1247-0. PMID: 27142195.
  9. Shabanzadeh A.P., D’Onofrio P.M., Monnier P.P., Koeberle P.D. Targetingcaspase-6 and caspase-8 to promote neuronal survival following ischemic stroke.Cell Death Dis 2015; 6: 1–13. doi: 10.1038/cddis.2015.272. PMID: 26539914.
  10. Sergeeva S.P., Savin A.A., Litvitskiy P.F. [A role of the Fas system in thepathogenesis of ischemic stroke]. Zh Nevrol Psikhiatr Im S S Korsakova. 2016;116 (3 Pt 2): 3–8. PMID: 27296794. (In Russ).
  11. Niu F.N., Zhang X., Hu X.M. et al. Targeted mutation of Fas ligandgene attenuates brain inflammation in experimental stroke. Brain, behavior,and immunity 2012; 26(1): 61–71. doi: 10.1016/j.bbi.2011.07.235.PMID: 21802508.
  12. Hoke M., Schillinger M., Zorn G. et al. The prognostic impact of solubleapoptosis-stimulating fragment on mortality in patients with carotid atherosclerosis.Stroke 2011; 42: 2465–2470. doi: 10.1161/STROKEAHA.110.611301.PMID: 21757675.
  13. Mahovic D., Zurak N., Lakusic N. et al. The dynamics of soluble Fas/APO1 apoptotic biochemical marker in acute ischemic stroke patients. Advances inmedical sciences 2013; 58(2): 298–303. doi: 10.2478/ams-2013-0014. PMID: 24277959.
  14. Brott T., Adams H.P., Olinger C.P. et al. Measurements of acute cerebralinfarction: a clinical examination scale. Stroke 1989; 20(7): 864–870. PMID: 2749846.
  15. Sulter G., Steen C., De Keyser J. Use of the Barthel index and modifiedRankin scale in acute stroke trials. Stroke 1999; 30(8): 1538–1541. PMID: 10436097.
  16. Martin-Villalba A., Herr I., Jeremias I. et al. CD95 ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons. The Journal of neuroscience 1999; 19(10):3809–3817. PMID: 10234013.
  17. Maas M.B., Furie K.L. Molecular biomarkers in stroke diagnosis and prognosis.Biomarkers in medicine 2009; 3(4): 363–383. doi: 10.2217/bmm.09.30.PMID: 20160867.
  18. Blankenberg F.G., Kalinyak J., Liu L. et al. 99mTc-HYNIC-annexin VSPECT imaging of acute stroke and its response to neuroprotective therapy withanti-Fas ligand antibody. European journal of nuclear medicine and molecularimaging 2006; 33(5): 566–574. doi: 10.1007/s00259-005-0046-6. PMID: 16477433.
  19. Sairanen T., Karjalainen-Lindsberg M.L., Paetau A. et al. Apoptosis dominantin the periinfarct area of human ischaemic stroke – a possible target ofantiapoptotic treatments. Brain 2006; 129(1): 189–199. doi: 10.1093/brain/awh645. PMID: 16272167.

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Copyright (c) 2017 Sergeeva C.P., Savin A.A., Arkhipov V.V., Gul’tyaev M.M., Breslavich I.D., Litvitskii P.F.

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