| Objective: Epilepsy is the repeat-paroxysmal obstacle of brain function as a result of nerve cells'excessive discharge. Among the epileptics, the damage of the cognitive function is familiar. As compared with adults, children are not only prone to have epilepsy, but also to have the damage of the cognitive function, because the mechanism of excitability and restrainability hasn't been balanceable in their puerile brains. Whether the damage of the cognitive function appears or not and it's degree relate to many factors, such as the age when the child had the epilepsy, style of the epilepsy, how many years since they got it and the frequency of the spasm, long-term application of antiepileptic drugs (AEDs), etc. Because AEDs is the preferred method to treat the epilepsy,and it must be taken for long , we pay special attention to the damage of the cognitive function by AEDs. The research outcome has indicated: Traditional AEDs can damage the cognitive function of epileptics, for example, phenytoin (PHT), clonazepam (CZP), phenobarbital (PB) and so on. Oxcabazepine (OXC) is a new antiepileptic drug which has been authorized to import and use by FDA in 2004. We have not found the interrelated reports about the effect of OXC upon the cognitive function in our country, and the reports in other countries are very little. In order to reduce the damage of the cognitive function by AEDs and estimate the effect of OXC on the cognitive function scientifically, we adopt the method of animal experiment and make models of epileptic young rats using the pentylenetetrazol, then describe their electroencephalograms. The epileptic rats are classed into three groups and are given oxcarbazepine, phenobarbital and 0.9% sodium chloride respectively. In three phases of the experiment, we will observe the change of the cells'form and appraise their cognitive functions by Morris water maze test comparing with the anti-epileptic rats. Before the Morris water maze test, we will check their sensibilities and movements by open field test, inclined plane test and over hanging test for getting rid of the experiment errors. Through discussing the effect of the oxcarbazepine upon the cognitive function of epileptic young rats, we'll offer the theoretical foundations of its choosing for epileptic children in clinic.Methods:1 Making modelsFifty healthy male Sprague-Dawley rats of three weeks old, each of them weights 50±10g. After feeding them one week, every rat has to pass through three place navigation tests. Then, eligible rats will be made into models. After filtering, we get 45 eligible rats. We class the rats into six groups randomly based on the grade of the place navigation tests: Control (number: 6), PB (number: 6), OXC (number: 6), EP (number: 12), EP+PB (number: 6) and EP+OXC (number: 6). In the process of making models, we will get rid of the several rats which have died or can not accord with the experimental requests, then use other rats to supply for guaranteeing the number of every group. EP group is classed into two ("a"and"b") little groups:"a"group will be checked the cognitive functions,"b"group will be observed the change of cells'form.EP Models: The rats of EP, EP+PB and EP+OXC three epileptic models will be injected the pentylenetetrazol (60 mg/kg/d, 5 days). The successful models should arrive at IV-V level based on the Racine standard; at the same time, the rats of Control, PB and OXC three anti-epileptic models will be injected 0.9% sodium chloride (the same dose, 5 days).2 Pour stomachFrom the second day of making epilepsy, the rats of OXC and EP+OXC two groups will be given OXC (80mg/kg ) every day; the rats of PB and EP+PB two groups will be given PB (50mg/kg) every day; the rats of Control and EP two groups will be given 0.9% sodium chloride every day.3 Making sampleBefore every check of the cognitive function, we choose 2 rats from"b"group of EP to narcotize, pour something to fix them, cut off the heads and get the brains, make piece and offer HE coloration and so on to observe the change of cells'form through microscope. 4 The check of the cognitive function and the sensibilities and movementsOn the two time nodes of after 24 hours of making epilepsy and taking medicine 7 days, we carry through the check of sensibilities and movements respectively, including open field test, inclined plane test and over hanging test; In the three time phases of taking medicine 4-7 days, 11-14 days and 18-21 days, we carry through the Morris water maze test respectively which lasts 4 days (the first and second day are the place navigation test which includes five series; the third day is the spatial probe test; the firth day is the work memory test ).5 ElectroencephalogramAfter finishing the test of the cognitive function, we choose 2-3 rats from anti-epileptic and epileptic models respectively to describe their electroencephalograms. Narcotizing rats and fixing them on the stereotaxic apparatus, we put the electrodes in cortexes and hippocampus symmetrically. After the rats wake, anti-epileptic models will be described normal electroencephalo -grams, and epileptic models will be described epileptic electroencephalograms after injecting the pentylenetetrazol and having the epilepsy.Results:1 Epileptic spasmThe rats of every epileptic model groups have the spasms of different levels, so making models have succeeded.2 The observing of cells'form Through microscope, we can observe the denaturalization and putrescence of nerve cells in the hippocampus. As time goes on, the number of the denaturalization and putrescence cells becomes fewer than before.3 The check of the cognitive function and the sensibilities and movements3.1 The check of the sensibilities and movementsOn the two time nodes of after 24 hours of making epilepsy and taking medicine 7 days, to the rats of EP, EP+PB and EP+OXC three epileptic models, the number of moving grids, the time of standings, the number of the dejecta and the ability of going round and hanging are not found statistical difference (P>0.05) comparing with the rats of Control group.3.2 The Morris water maze test3.2.1 Place navigation testThe first phase test(taking medicine 4-5 days): It includes five series. The latent period finding the flat of EP group is longer then the Control group and the difference is notable in the first series test (P< 0.05); The latent period finding the flat of EP+PB group is longer then the Control group and the difference is notable in the first and second series test (P< 0.05; P< 0.01); The grades of other groups are not found statistical difference comparing with the Control group in the five series tests (P>0.05). In the statistics of the studying rate of progress, only the grade of EP+PB group is worse then the Control group, and the difference is notable (P< 0.05). The second and third phase tests(taking medicine 11-12 and 18-19 days):We get the same results. Among the five series tests, the latent periods finding the flat of every group are indifferent statistically (P>0.05). In the statistics of the studying rate of progress, only the grade of EP+PB group is worse then the Control group, and the difference is notable (P< 0.05).3.2.2 Spatial probe testThe first phase test(taking medicine 6 days): The time settling in the flat'quadrant of EP and EP+PB group is shorter then the Control group, and the difference is notable (P< 0.05); but among other groups, we do not find statistical difference comparing with the Control group (P>0.05).The second and third phase tests(taking medicine 13 and 20 days): We get the same results. Only the time settling in the flat'quadrant of EP+PB group is shorter then the Control group, and the difference is notable (P< 0.05).3.2.3 Work memory testAmong the three phase tests(taking medicine 7, 14 and 21 days), the latent periods finding the flat of every group are indifferent statistically comparing with Control group (P>0.05).4 ElectroencephalogramThe electroencephalogram of the epileptic model groups appears representative sharp-slow combining wave, sharp wave and spike wave. The electroencephalogram of the anti-epileptic model groups is normal.Conclusions: 1. The spasm of epilepsy results in the denaturalization and putrescence of nerve cells in the hippocampus.2. Epilepsy doesn't affect the sensibilities and movements of young rats, but it can affect their cognitive functions transitorily. It mainly embodies the capability of the spatial orientation and the long-term memory, however, the studying rate of progress and the capability of the short-term memory have not been damaged in evidence.3. Phenobarbital can affect the studying rate of progress and the capability of the long-term memory of young rats with pentylenetetrazol-induced epilepsy, but its effect on the capability of the short-term memory is not obvious; and normal young rats do not have the obvious damage of the cognitive function after they took phenobarbital.4. Oxcarbazepine can alleviate the cognitive function damage (especially on the capability of the spatial orientation and the long-term memory) of epileptic young rats in the early stage which the denaturalization and putrescence are serious, and normal young rats do not have the obvious damage of the cognitive function after they took oxcarbazepine. |
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