Establishment And Study Of Model Of Chronic And Partial Epilepsy Induced By Aluminum Hydroxide In Cat's Motor Cortex

Objective: Epilepsy is cerebral chronic functional disturbance syndrome by multifold etiopathogenisis, is abnormal discharage of neuron. Epilepsy show multifold functional disturbance as movement, aesthema, consciousness, mind, etc. The result induce to heavy burden for family and society. Now epileptic therapy apart from traditional medicine and operation also Gamma Knife radiosurgery. Because of Gamma Knife radiosurgery needn't open skull, it is regarded as not only safe available method but also minor impairment. The investigative emphasis is that how much therapeutic dose is suitable, that not only apoptosis happen only the I-II layer of cerebral cortex without other four layer but also lesser gliocyte cicatricle emerge. On account of above-mentioned reason ,we establish the model of chronic and partial epilepsy induced by aluminum hydroxide in animal motor cortex, to serve both surgical operation in eloquent cortex and the choose of therapeutic dose in Gamma Knife radiosurgery. Among several animal models of chronic and partial epilepsy , Metal animal models is the best and aluminum Hydroxide is most suitable metal. About the choice of animal, we choose cats as experimental animal, because cats are active, cats'motor cortexs are developed and similar with human being. After establish and study the model of chronic and partial epilepsy induced by aluminum hydroxide in cat's motor cortex. The first we observe epileptic seizure and record the change of Electroencephalogram(EEG) at different time point; The second the tissue of epileptogenic focus are observed by the light microscope and eletron microscope; The third the contents of Superoxide dismutase(SOD) and Malondialdehyde(MDA) in the motor cortex are measured, then we can establish some theoretical foundation for researching the pathogenesy of epilepsyMethods: Twenty healthy male domestic cats, weigh 2500~3500 grams, were randomly divided into the aluminum hydroxide -induced group and normal saline control group, cats were anesthetized using 3% Nembutal, then 50 microliter of sterile 8% aluminum hydroxide or normal sodium were injected into the sigmoid gyrus after opened their cranium. We observed their behavioral changes after the procedure everyday, we had continuous observed three to five hours in the everyday of twenty weeks, including living habit, eating and epileptic seizure. Using MS4000U Biological Signals Quantitative Recording And Analyzing System recorded and analysed dynamic changes of EEG in the epileptogenic focus of the models of animal at two week, four week, six week, eight week, twelve week, sixteen week, twenty week after the operation. The epileptogenic focus were cutted and observed by the light microscope and eletron microscope after twenty weeks, at the same time the content of SOD and MDA in the motor cortex were measured by spectrophotometer.Results: 1 Ethology: The appetite of the two groups decreased significantly atter the operation and the spirit was dispirited. they have recovered normal eating and the spirit was improved after three days, six cats was found epileptic seizure in the aluminum hydroxide -induced group from 11 to 14 weeks, they showed simple partial seizures, the time of seizures lasted from ten second to five minutes. The epileptic seizure hadn't been observed in normal saline control group .2 Results of EEG: Spike wave wasn't monitored in the aluminum hydroxide -induced group from two weeks to six weeks after aluminum Hydroxide was injected. Epileptiform spike activity was first detected at the eight weeks after Aluminum hydroxide was injected, frequency of spike wave is 4.7±1.3 per minute. Severe Spike wave was detected at the twelve weeks, frequency of spike wave is 37.2±8.4 per minute. Spike wave was detected at the sixteen and twenty weeks, frequency of spike wave is 9.2±2.4 per minute and 8.6±2.4 per minute. Spike wave wasn't detected in the normal saline control group from the beginning to the end.3 Results of HE stain: The epileptogenic focus of the aluminum hydroxide -induced group showed that the quantity of neurons was decreaded, the neurons showed degeneration and necrosis. Glial cells were hyperplastic in the motor cortex, and you could find neurons was phagocytized by glial cells. Micrangium was dilated and congestive.4 Ultrastructure of nerve cells: The epileptogenic focus of the aluminum hydroxide -induced group showed that cytoplasm of neurons were apparent swelling, the quantity of organelles were decreasing, a part of membrane of the bulk of the sporadic mitochondrias'cristae were coalescesed or disappeared, rough endoplasmic reticulum(RER) were expanded and you could observe apparent degranulation phenomenon, a part of nuclear membrane were coalescesed, unclear or disappear. the quantities of pinocytosis vesicle were decreased, on one side of micrangiums were swollen, neural myelin sheath were hyperplastic apparently, and the thickness was inhomogeneous, the layers structure had the phenomenon of delamination, the quantities of microfilament and microtubule were decreased.5 Contents of SOD, MDA: Contents of SOD was 147.68±24.29U/mgprot on the aluminum hydroxide -induced group. Contents of SOD was 175.01±25.29U/mgprot on the normal saline control group. Contents of MDA was 0.5082±0.1616umol/gprot on the aluminum hydroxide -induced group. Contents of MDA was 0.2896±0.0528umol/gprot on the normal saline control group. Contents of SOD was lower apparently on the Aluminum Hydroxide -induced group than the normal saline control group. Contents of MDA was more apparently on the aluminum hydroxide -induced group than the normal saline control group.Conclusions: 1 The models of the aluminum hydroxide -induced group showed simple partial seizures, continued spike wave and changes of pathology, the results indicated the models of chronic and partial epilepsy induced by Aluminum hydroxide in cat's motor cortex was successful.2 Epileptiform spike activity was first detected at the eight weeks after aluminum hydroxide was injected, severe Spike wave was detected at the twelve weeks, spike wave still was detected at the twenty weeks. Maybe Spike wave were peak time at the twelve weeks.3 The pathological mechanism of epileptogenic focus on the Aluminum hydroxide -induced group was that neurons were degeneration and necrosis, glial cells were hyperplastic in the motor cortex, micrangium was dilated and congestive etc. We thinked about the pathological changes of epileptogenic focus perhaps were structural basic of epileptic seizure and spike wave.4 Contents of SOD was lower apparently on the Aluminum Hydroxide -induced group than the normal saline control group. Contents of MDA was more apparently on the Aluminum Hydroxide -induced group than the normal saline control group. The result showed the system of oxidation and antioxidation were disequilibrium on the tissue of epileptogenic focus, producted excess oxygen free radical, and strengthened to injure normal cerebral cortex. The SOD as a biocatalyst for oxygen free radical was decreased by excess consume, the result was that cells of nerve were injured, then denaturation and necrosis, further promoted the develop of epilepsy.