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

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Abstract

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

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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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