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

Abstract

The aim of the present study was to investigate neuroprotectiveeffects of erythropoietin (EPO), and ischemic pre- and postconditioningin a rat model of focal cerebral ischemia. Adult maleWistar rats were subjected to a 40-min bilateral common carotidartery (CCA) occlusion and permanent ligation of the corticalbranch of the middle cerebral artery (MCA). Preconditioningprotocol consisted of either one or two episodes of 5-min CCAocclusion with 5-min reperfusion prior to test ischemia (PreCon 1and PreCon 2). Postconditioning (PostCon) protocol comprised10 episodes of 10-s CCA occlusion followed by 10-s reperfusionintervals. After modelling of ischemia, brain infarct occurred predominantlyin the left temporal cortex. EPO administration atdoses 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 reducedthe severity of neurological deficit (p0.05). EPO at both doses,PreCon 1 and PreCon 2 were shown to ameliorate postischemiccerebral blood flow. Brain edema was significantly smaller in theEPO arm at dose of 5000 U/kg, and in PreCon 2 and PostCongroups. Thus, PreCon and PostCon, as well as prior administrationof EPO result in neuroprotective effect in focal cerebralischemia, and EPO has a dose-dependent protective effect. EPOand PreCon reduce the severity of postischemic hypoperfusion.

Keywords

• focal brain ischemia
• stroke
• necrosis
• preconditioning
• postconditioning
• erythropoietin
• neuroprotection