الفهرس 
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Abstract
Epilepsy is a widely spread disease with a recurrent spontaneous seizure. Several epidemiological studies indicate mortality in epileptics. Antiepileptic drugs (AEDs) are used to reduce the frequency of seizures. This is done in high doses and for long time, which is always accompanied with side effects. Lacosamide (LCM) is a widely used antiepileptic drug that has extensive anticonvulsive effect. This study aims to use a Melissa officinalis extract (MOE) as a natural product with anticonvulsant effect and comparing its effect with the used drug (lacosamide) to reduce the oxidation and reduce the drugs-side effects.
In this study 105 male albino rats (Rattus norvegicus) weighing about 130 -170 g were used as experimental animals in the present investigation. They came from the National Research Center’s animal house in Cairo, Egypt. They were kept under surveillance for ten days prior to the start of the experiment to rule out the possibility of an infection. The animals were kept in metal (stainless steel) cages at room temperature (25°C). Moreover, exposed to 12 hours of regular light every day. Rats were given access to water and a well-balanced standard meal on a daily basis. The rats were randomly classified into six groups.
Control group: considered as normal control. They were orally given distilled water six days/ week by gastric intubation for four weeks.
LCM group: rats were administered with lacosamide orally six days/week for two weeks, and considered as the drug treated group. Then continued the experiment till the end by the same route as the control.
MOE group: rats were treated with Melissa extract orally six days/ week for two weeks. Then continued the experiment till the end by the same route as the control.
Pilo group: rats were injected with pilocarpine then orally given distilled water six days/week till the end of the experiment as the control group.
Pilo+ LCM group: rats were injected with pilocarpine. After two hrs they were treated with lacosamide for two weeks. Then continued the experiment till the end by the same route as the control.
Pilo+ MOE group: rats were injected with pilocarpine. After two hrs they were treated with MOE for two weeks. Then continued the experiment till the end by the same route as the control.
After that, the brain was excised and dissected for biochemical and histopathological studies. Epileptogenesis was assured by measuring the level of neurotransmitters, electrolytes, ion transport channel, and oxidation process in the brain of both treated and infected rats. Also fixed brain tissues and stained by hematoxylin and eosin staining .Then stained this brain by GFAP staining.
The obtained data of the above investigation obtained these results:
1- An ameriolative effect in neurotransmitters in groups five and six that treated by lacosmide and Melissia.This groups show good results when compared to group four (Pilocarpine injeted group).
2- Electrolytes (Na+, K+, Ca2+ and Mg2+) showed good result in the treated groups. There is an increase in intracellular potassium and magnesium whereas sodium and calcium decreased after treatment.
3- Ion transport channels also show ameriolative effect in the treated groups. CLCN2 and VGKC increased in the epileptic treated groups (Pilo+LCM and Pilo+MOE) while SCNNa1 and VGCC decrease.
4- IGF1 and BDNF showed decreased levels in the epileptic groups that treated by melissia and lacosamide.
5- The activation therine/therionine, mTOR pathway stated from the extracellular signal (MAPK) then cAMP, PI3K and Akt are all expressed amelioration and decreased expression after LCM and MOE treatments after piocarpine injection.
6- The oxidation and antioxidant defence mechanism represented by HO-1, Nrf2 and the antioxidant enzyme show good result in epileptic treated groups when compared to the psitve pilocarpine epileptic one.
7- Inflammattory mediators (PGE2 and COX-2) show low level in the pilocarpine treated groups.
8- Pilocarpine induced several histopathological alterations in hippocampus and cerebellum, but marked amelioration of histopathological changes were observed after treatment of epileptic group with LCM or MOE.
9- Immunohistochemical study and image analysis revealed a significant increase in GFAP in pilocarpine injected group and significantly ameliorated after LCM or MOE treatment. Notably, the effect of MOE on GFAP expression was significant when compared with LCM in the hipocampus. As astrocytes act as a neuroprotective sheath that fill any defect in the nervous tissues.
In conclusion, Melissia officinalis extract expressed an ameliorative effect in the pilocarpine treated rats. Indicating antiepileptic mechanisms by ameliorating the neuronal electrical cell imbalance and increasing energy depletion. Exerting antioxidant, anti-inflammatory and antiepileptogenic effects. This plant extract may be used for treatment after further studies.