The Protective Effect Of Edaravone On Total Cerebral Ischemical Reperfusion Injury In The Rabbits With Cardiac Arrest

BackgroundAfter cardiopulmonary resuscitation, intoxication, shock , intervention, thrombolysis therapy and so on, severe brain function disorder usually comes occur due to the ischemical reperfusion injury. A large amount of basic and clinical researches were made for, but there has no breakthrough progress come still. The study of molecular biology manifested that multiple factors participate in the process of the cerebral ischemical reperfusion injury, apoptosis, free radical damage, calcium overload, toxicity of excitatory amino acids and others have been validated by most experiments. The death of nerve cell after brain injury can be divided into two types: cellular necrosis caused by primary injuryand apoptosis due to secondary injury. The primary injury is unavoidable, so to block the secondary injury in early stage become the important turning point in the protection of brain injury.Ischemia and hypoxia after heart arrest can lead to the primary injury to the brain, while the large amount of active oxygen is one of the main initiation factors that can cause the secondary lesion after reperfusion injury. Because of the high concentration with the poly-unsaturation fatty acid, short of the ability of antioxidation, brain tissues have a particular sensitivities when faced to the lipid peroxidation. Oxyradical can damage the brain cell through lipid peroxidation, protein oxygenation, hydrolization, exhausting ATP, demolishing DNA etc, the damages ranged from transforming the celluar membrane to cytoclasis. Further, direct lipid peroxidation can change the contractibility of vascular, and make tissue damage serious more. Oxyradical can activation the related gene of apoptosis also and lead to the secondary delayed neuronal death.Edaravone is a new drug with protective effect on anti free radical , usually used to cure focal brain ischemia such as cerebral infarction in clinics, it can reduce oxyradical damage, regulate apoptosis, protect brain tissue from being injured.On total cerebral ischemical reperfusion injury caused by cardiopulmonary resuscitation, more free radical were produced, resultin secondary injury to the brain tissues more severe and more extensive.We presume the Edaravone to be used in the early stage of reperfusioninjury, possibly could relieve the degree and block the process of thesecondary injury.Through this experiment we intend to initially probe the protectiveeffect of Edaravone on total cerebral ischemiacal reperfusion injury inrabbits with cardiac arrest.ObjectiveTo investigate the protective effect of Edaravone on total cerebralischemical reperfusion injury in rabbits with cardiac arrest.MethodsAdult rabbits have been divided into 5 groups: no electric stimulus and no cardiopulmonary resuscitation as control group, use normal saline after electric stimulus and cardiopulmonary resuscitation as model control group, and 1mg/kg, 2mg/kg, 3mg/kg doses of Edaravone therapeutic groups. After electric stimulus induced ventricular fibrillation and cardiopulmonary resuscitation, the model of total cerebral ischemical reperfusion injury with cardiac arrest were produced. Different doses of Edaravone or normal saline were interfered in, then detect the serum level of S100B with ELISA, the Bcl-2 gene in brain by immunohistochemistry, the pathology change of substantial alba and medullary sheath with specific stain, and measure the moisture capacityof brain tissue. ResultsThe serum level of S100B elevated significantly after reperfusion injury, the model control group and the different doses of Edaravone therapeutic groups are significantly higher than that of the control group; level of S100B in all different doses Edaravone groups are significantly lower than that in the model control group; among different doses Edaravone groups level of S100B seem to in downtrend with the dosage increase.The Bcl-2 gene express increased after reperfusion injury, and in the model control group and the different doses of Edaravone therapeutic groups are significantly higher than in control group; there was no significantly difference between the model control group and the different doses of Edaravone therapeutic groups; among the different doses of Edaravone therapeutic groups, no significantly difference were found too.The pathological changes in the model control group found the brain cell show cytomorphosis, cell nucleus anachromasis, myelinoclasis; changes in the different doses of Edaravone therapeutic groups are more slightly; among different doses of Edaravone therapeutic groups pathological changes are similar.The edema of brain tissue rise after reperfusion injury, and in the model control group and in the different doses of Edaravone therapeuticgroups are higher than in the control group significantly; the edema of the model control group higher than in the different doses of Edaravone therapeutic groups significantly; among different doses of Edaravone therapeutic groups, 1mg/kg Edaravone group higher than in 3mg/kg Edaravone group significantly. ConclusionThe study reveals that Edaravone can decrease brain cell edema, relief pathological lesion, Edaravone has protective effect on total cerebral ischemical reperfusion injury on the rabbit with cardiac arrest.