| Objective: Epilepsy is one of the common, chronic diseases with seizures in central nervous system. It is sudden, transient cerebral dysfunction caused by super synchronic and abnormal discharges of cerebral cells. The most obvious clinical symptoms of epilepsy are epileptic seizures and various electroencephalogram characteristics. Antiepileptic drugs are the major diplomacy of epilepsy therapy. Some epileptics need to cpalend AEDs long-time even lifetime. A lot of epileptic have failure of memory. Some investigation indicated that 30%~40% epileptic have failure of memory. The effect factors of epileptic's quality of life are types, frequency and age of epilepsy and AEDs. AEDs are a major factor. Nitric oxide is the messenger molecule in central nervous system. NO have the double-acting of conservation and impair. NO participates multitude physiological and patho-biology contribution. NO has consequence contribution in epilepsy and learning and memory. nNOS is the rate-limiting enzyme of NO composition. In most conditions, nNOS expresses at low level. In patho-condition nNOS expresses at high level. A pond of NO have toxigenicity role. But the research about the relation of nNOS to cognition deficient rats kindled by Pentylenetetrazole and anti-epileptic drugs has not been reported heretofore. Our study is based on rats of chronic epilepsy kindled by Pentylenetetrazole which were treated with 0.9% saline or Lamotrigine or Divitamins Notonginseng and Cinnarizine Capsules. We have accomplished our study by observing animal behaviors, electroencephalo- gram (EEG), Morris water maze test and immunocytochemistry. We evaluate the impactions of cognitive function and the expression of nNOS in the hippocampus of rats kindled by Pentylenetetrazole which were treated by Lamotrigine and Divitamins Notonginseng and Cinnarizine Capsules. So we proposed a theory for studying the mechanism of learning and memory disorder about epilepsy and anti-epileptic drugs in clinic work.Methods1 animal pattern60 mature male Sprague-Dawley (SD) rats (weight 200±20 g) are selected by MWMT before being made pattern. The eligibility was separated into five random groups: control group (group A, n=10; group E, n=10), PTZ + saline group (group B, n=10), PTZ + LTG group (group C, n=10), PTZ + DNCC group (group D, n=10).1.1 Made chronic epilepsy patternThe rats in testing group are received 1% PTZ 35mg/kg/d, the rats in control group were received the same number of saline injections. After 15 days or so, observing rats'behaviors and noting their actions one by one according to the Racine scale. Fully kindled rats, defined as rats presenting at least 3 times stageⅡseizures or stageⅢseizures.1.2 Drug therapyAfter rats fully kindled, rats in control group and B,D,C were treated with corresponding drugs: 0.9% saline , 0.9% saline, Lamotrigine and Divitamins Notonginseng and Cinnarizine Capsules twice every day .They were treated about 15 days.2 ElectroencephalogramAfter the rats were fully kindled, we gave 2-3 rats electr- oencephalogram examination in every group randomly. The aim was to determine kindling effects. Using stereotaxic apparatus, rats were implanted with a bipolar electrode made from Teflon-coted stainless steel wires in the two side perforant path. When the rat waked, we made the model with the methods above-mentioned.3 Examination of cognitive functionWe carried out Morris water maze test to exam the abilities of learning and memory of rats. The Searching platform latency and searching time and staying time were thought as learning and memory records of rats.4 ImmunocytochemistryAfter rats were anesthetized, we perfused and fixed through the ascending aorta of heart with 4% citromint. After that, the telencephalon was taken out. Then the slides were incubated with nNOS polyclonal antibody, these specimens were incubated with the seconds antibody, avidin-biotin-perxidase complex. Among these approaches, we should wash these specimens with PBS, the results were visualized by using diaminobenzidine as chromogen.Result1 Ethology of epilepsyRats in every experiment group had epilepsy attack of different degree. After intragastric handling, episode of rats in group D decreased obviously.2 electroencephalogramThe electroencephalogram of rats of control group showed moreαwaves and lessθwaves. The double sides are symmetry. The electroencephalogram of chronic epilepsy analogue rats showed representative acantho slow wave, vertex sharp transient wave, sharp wave.3 Detection of cognition function3.1 Comparison of searching platform latency of every time among the groups3.1.1 Comparison of SPL in every groupGroup A: It has significant difference (P<0.01) between 1st time and 3rd, 4th, 5th, 6th time. It has significant difference (P<0.05) between 2nd time and 3rd, 4th, 5th, 6th time. Group B: It has significant difference (P<0.01) between 1st time and 2nd, 3rd, 4th, 5th, 6th time. Group C: It has significant difference (P<0.01) between 1st time and 3rd, 4th, 5th, 6th time. Group D: It has significant difference (P<0.01) between 1st time and 3rd, 4th, 5th, 6th time. It has significant difference (P<0.05) between 1st time and 2nd time. Comparison of other times in every group sugges- ted that no significant difference (P>0.05).3.1.2 Comparison of SPL among the groupsIt has significant difference (P<0.05) between group C, D and group B in the 6th time. Comparison of other groups in every time suggested that no significant difference (P>0.05).3.2 Comparison of searching platform latency of every day among the groups3.2.1 Comparison of SPL in every groupGroup A: It has significant difference (P<0.01) between 1st day and 3rd, 4th day. It has significant difference (P<0.01) between 2nd day and 3rd, 4th day. Group B: It has significant difference (P<0.05) between 1st day and 2nd day. It has significant difference (P<0.01) between 1st day and 3rd, 4th day. It has significant difference (P<0.05) between 2nd day and 3rd, 4th day. Group C: It has significant difference (P<0.01) between 1st day and 3rd, 4th day. Group D: It has significant difference (P<0.01) between 1st day and 2nd day. It has significant difference (P<0.05) between 2nd day and 3rd, 4th day. Comparison of other days in every group suggested that no significant difference (P>0.05).3.2.2 Comparison of SPL among the groupsIt has no significant difference (P>0.05) between test group and control group in the 1st, 2nd, 3rd day. It has significant difference (P<0.05) between group B and group C in the 4th day. It has no significant difference (P>0.05) between group B and group D in the 4th day.3.3 Comparison of Searching time and staying timeIt has no significant difference (P>0.05) between group A and group B, C, D. It has significant difference (P<0.05) between group B and group C, D. It has no significant difference (P>0.05) among A, C, D.4 immunohistochemistry drum dyeingThe endochylema of nNOS masculine neuron in the hippocampus submits yellow brown. The cell membrane's outline is clearly. The nucleus is distinctness coloration or becoming appearance of vacuolus. The expression of nNOS immunity masculine production was enhanced in group E, A, D, B, C one by one.Conclusion1 Making epilepsy rats treated with lamotrigine successfully.2 Lamotrigine may control the epilepsy attack of the rats. It can release the damage of cognitive function, and elevate cognitive function of epilepsy rats. Divitamins Notonginseng and Cinnarizine Capsules may elevate the learning and memory ability properly, but it hasn't antiepileptic function.3 Physiological dose of NO has significance contribution on learning and memory ability.4 The damage of cognitive function are related to the over expression of nNOS. The overdose NO has nervous toxic action. 5 Lamotrigine may decrease the expression of nNOS of epilepsy rats. It protects the neurons functions.
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