Endogenous neuroprotection during focal brain ischemia in rats: erythropoietin, ischemic pre- and postconditioning

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The aim of the present study was to investigate neuroprotective effects of erythropoietin (EPO), and ischemic pre- and postconditioning in a rat model of focal cerebral ischemia. Adult male Wistar rats were subjected to a 40-min bilateral common carotid artery (CCA) occlusion and permanent ligation of the cortical branch of the middle cerebral artery (MCA). Preconditioning protocol consisted of either one or two episodes of 5-min CCA occlusion with 5-min reperfusion prior to test ischemia (PreCon 1 and PreCon 2). Postconditioning (PostCon) protocol comprised 10 episodes of 10-s CCA occlusion followed by 10-s reperfusion intervals. After modelling of ischemia, brain infarct occurred predominantly in the left temporal cortex. EPO administration at doses of 2500 and 5000 U/kg 30 minutes prior to ischemia, PreCon 1 and PostCon reduced significantly the infarct size (p <0.05) compared to controls. EPO at dose of 5000 U/kg reduced the severity of neurological deficit (p<0.05). EPO at both doses, PreCon 1 and PreCon 2 were shown to ameliorate postischemic cerebral blood flow. Brain edema was significantly smaller in the EPO arm at dose of 5000 U/kg, and in PreCon 2 and PostCon groups. Thus, PreCon and PostCon, as well as prior administration of EPO result in neuroprotective effect in focal cerebral ischemia, and EPO has a dose-dependent protective effect. EPO and PreCon reduce the severity of postischemic hypoperfusion.


About the authors

A. A. Shmonin

Saint-Petersburg I.P. Pavlov State Medical University; V.A. Almazov Federal Centre of Heart, Blood and Endocrinology

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

I. Y. Panov

Saint-Petersburg I.P. Pavlov State Medical University

Email: platonova@neurology.ru
Russian Federation

A. V. Simanenkova

Saint-Petersburg I.P. Pavlov State Medical University

Email: platonova@neurology.ru
Russian Federation

M. S. Prosvirnina

Saint-Petersburg I.P. Pavlov State Medical University

Email: platonova@neurology.ru
Russian Federation

S. S. Chekanov

Saint-Petersburg I.P. Pavlov State Medical University

Email: platonova@neurology.ru
Russian Federation

E. V. Melnikova

Saint-Petersburg I.P. Pavlov State Medical University

Email: platonova@neurology.ru
Russian Federation

T. D. Vlasov

Saint-Petersburg I.P. Pavlov State Medical University

Email: platonova@neurology.ru
Russian Federation


  1. Власов Т.Д., Байса А.Е., Шмонин А.А. и др. Защитный эффект ишемического прекондиционирования при фокальной ишемии головного мозга крысы различной продолжительности. Клиническая патофизиология 2008; 1: 54–57.
  2. Власов Т.Д., Коржевский Д.Э., Полякова Е.А. Ишемическая адаптация головного мозга крысы как метод защиты эндотелия от ишемического/реперфузионного повреждения. Росс. физиол. журн. им. И.М.Сеченова. 2004. 90: 40–48.
  3. Галагудза М.М. Сравнительная оценка кардиопротективной эффективности локальной и дистантной ишемической адаптации миокарда. Дис. … канд. мед. наук. СПб, 2001.
  4. Захаров Ю.М. Негемопоэтические функции эритропоэтина. Росс. физиол. журн. им. И.М.Сеченова 2007; 93: 592–608.
  5. Строев С.А., Самойлов М.О. Эндогенные антиоксиданты и гипоксическая толерантность мозга. СПб: Институт физиологии им. И.П.Павлова РАН, 2006.
  6. Dirnagl U., Meisel A. Endogenous neuroprotection: mitochondria as gateways to cerebral preconditioning? Neuropharmacology 2008; 55: 334–344.
  7. Ehrenreich H. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol. Med. 2002; 8: 495–505.
  8. Garcia J.H., Wagner S., Liu K.-F., Hu X.-J. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion: statistical validation. Stroke 1995; 26: 627–635.
  9. Gross E.R., Gross G.J. Ligand triggers of classical preconditioning and postconditioning. Cardiovasc. Res. 2006; 70: 212–221.
  10. Erythropoietin and the nervous system novel therapeutic options for neuroprotection (ed. A. Höke) NY: Springer, 2006.
  11. Labiche L.A., Grotta J.C. Clinical trials for cytoprotection in stroke. NeuroRx: The Journal of the American Society for Experimental NeuroTherapeutics 2004; 1: 46–70.
  12. Leconte et al. Delayed hypoxic postconditioning protects against cerebral ischemia in the mouse, Stroke 2009; 40: 3349–3355.
  13. Malhotra S., Savitz S.I., Ocava L., Rosenbaum D.M. Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack. J. Neurosci. Res. 2006; 83: 19–27.
  14. Minnerup J. The efficacy of erythropoietin and its analogues in animal stroke models: a meta-analysis. Stroke 2009; 40: 3113–3120.
  15. Pignataro G., Scorziello A., Di Renzo G., Annunziato L. Postischemic brain damage: effect of ischemic preconditioning and postconditioning and identification of potential candidates for stroke therapy. FEBS J. 2009; 276: 46–57.
  16. Ren C., Gao X., Niu G. et al. Delayed Postconditioning protects against focal ischemic brain injury in rats. PLoS ONE 2008; 3 (12): 1–12.
  17. Wang J.Y., Shen J., Gao Q. et al. Ischemic postconditioning protects against global cerebral ischemia/reperfusion-induced injury in rats. Stroke 2008; 39: 983–990.
  18. Zhao H., Sapolsky R.M., Steinberg G.K. Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size after focal ischemia in rats. J. Cereb. Blood. Flow. Metab. 2006; 26: 1114–1121.
  19. Zhao H. Ischemic postconditioning as a novel avenue to protect against brain injury after stroke. J. Cereb. Blood Flow Metab. 2009; 29: 873–885.



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Copyright (c) 2017 Shmonin A.A., Panov I.Y., Simanenkova A.V., Prosvirnina M.S., Chekanov S.S., Melnikova E.V., Vlasov T.D.

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