Examination of the protective effects of clopidogrel use in rats with experimentally induced cerebral ischemia-reperfusion

In the list of causes for death stroke is the third rank following coronary heart diseases and cancers in all over the world. Ischemic stroke is the most common type of strokes. Ischemic stroke is a process accompanied by a variety of biochemical and immunological reactions secondary to the fall in cerebral blood flow. In the recent years major molecular, genetic, clinical and biochemical advances were recorded in ischemic stroke studies.Apoptosis is one of the most significant mechanisms in the reperfusion and secondary injury of the brain parenchyma after ischemia. There are a number of factors that start the events leading to cellular death in cerebral ischemia. For instance, increase in the intracellular calcium and free radicals, activation of the enzymes such as phospholipases, proteases, and endonucleases are the stimulants leading to apoptosis. The most important factor is the excessive increase in the intracellular calcium concentration. The ion channels in N-methyl-D-aspartate (NMDA) receptors increases the amount of Ca2+ entering into the cell and results with cell death. This causes specific gene transcriptions and protein synthesis. To decrease the effects of this pathway a number of studies were conducted with a number of agents such as ascorbic acid, alphatocopherol, and N-acetylcystein.Clopidogrel is a prodrug that disrupts platelet aggregation, prolongs bleeding time, and decreases blood viscosity by inhibiting the effect of ADP on the platelet P2Y12 receptors. In addition, introduction of the inflammatory properties of platelets and effects of the anti-platelet treatment on the inflammation markers were investigated. In this study, clopidogrel molecule was regularly administered to rats with induced ischemia-reperfusion for 5 days before and after the operation. Histopathological examinations were conducted in the brain tissues and the levels of oxidants and antioxidants were determined in the serum samples of decapitated rats. It was determined that the results in the clopidogrel administered rats showed significant antioxidant levels and histopathological examinations when compared to the control group.In conclusion, it is suggested that clopidogrelin might be effective in decreasing the effects of the ischemic stroke.Key words: Ischemic stroke, Clopidogrel, Rat