engleski

Erythropoietin treatment and ischemic stroke model in rats

Ischemic brain damage caused by stroke represents one of the leading causes of mortality and long-term disability in humans. It is a dynamic process that involves immediate excitotoxicity and oxidative stress followed by inflammation and apoptosis. Although significant advances have been made in understanding the mechanisms of ischemic brain damage, effective therapeutic strategy is still lacking. Recent findings showed that hematopoietic cytokine erythropoietin (Epo) has important non-hematopoietic functions, particularly in the brain. Epo has been identified as a neurotrophic and neuroprotective agent in a various experimental models of brain damage. However, the mechanisms of its neuroprotective effect are not clear and its therapeutic potential needs to be clarified. In the present study, we examined the effects of systemic administration of Epo on lipid peroxidation levels and antioxidant enzymes' (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) activities following ischemia/reperfusion in rats exposed to transient middle cerebral artery occlusion (MCAO). Materials and Methods: Male Hannover-Wistar rats (250-350 g) were subjected to MCAO for 1 hr, according to the procedure of DeLonga et al. (1989). After 23 hrs of reperfusion, ischemic animals were sacrificed and the levels of lipid peroxidation as well as SOD and GSH-Px activities were determined spectrophotometrically in the right and left hippocampus. Ischemic animals received either vehicle or erythropoietin (5000 IU/kg, intraperitoneally) immediately after or 3 hrs after ischemic procedure and were decapitated 23 hrs or 21 hrs later, respectively. Sham operated, vehicle treated animals were used as the control group. Results: Focal cerebral ischemia significantly increased the thiobarbituric acid-reactive substances (TBARS) levels, as well as SOD and GSH-Px activities in the right hippocampus when compared to the control group. Treatment with Epo significantly decreased the level and activities of above mentioned oxidative stress parameters. Similar dynamics of changes in lipid peroxidation and antioxidant enzymes' activities was found in the left hippocampus but values did not reach the level of significance. Conclusions: These results suggest that transient MCAO induced significant changes in lipid peroxidation levels and activities of SOD and GSH-Px in the right hippocampus. The results obtained after Epo treatment indicate its potential protective effect via the modulation of lipid peroxidation and antioxidant enzymes' activities. Acknowledgement: Supported by the Croatian Ministry of Sciences, Education and Sports, Grant 062-0620529-0518

Cerebral ischemia; Neuroprotection; Erythropoietin

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