Background and Purpose: Despite widespread research on epilepsy, the mechanism of its insidnece is still unknown. Since the activity of ATPase plays a vital role in changing ATP into AMP, and this substance can later turn into adenosine which is the most important endogenous anticonvulsant agent in brain, the effect of inhibition of ATPase on perforant path kindling was investigated in the present study.Methods and Materials: In this experimental study, animals were kindled by electrical stimulations of the perforant path (12 times a day with a frequency of 50 Hz and pulse duration of 1 millisecond). Upon kindling, behavioral and electrophysiologic measures of convulsions and filed potentials were recorded. For investigating the role of ATPase in animal groups, FPL 67156 was injected as the inhibitor of the ATPase after kindling stimulations ended each day. Kindled animals were 6, and there were 4 rats in other groups. Repeated measures ANOVA and Bonferoni test were used to compare the statistical quantities of fEPSP and PS of epilepsy creation in different groups of the study. Comparing the difference of paired pulses between groups was conducted by Bonferoni test. The five-stage convulsion of the groups was compared through Kruskall Wallis and Mann Whitney U tests. Statistical analyses were conducted in Prism 5.Results: The results indicated that ATPase inhibition (by injecting FPL 67156) causes no change in various behavioral stages of convulsion and daily afterdischarge duration following kindling (P>0.05); however, it affects synapsis formation, so that PS increases in comparison with the kindled group (P<0.05) and inceases the lowering of paired pulses (P<0.05).Conclusion: The results indicated that the activity of ATPase plays an inhibitory role on the formation in bringing about epiliepsy by kindling, so that by controlling it, it is facilitated.

Background: Almost 20% of epileptics are drug resistant. Studies have shown that lowfrequency repetitive transcranial magnetic stimulation (rTMS) is with therapeutic effectson epilepsy-affected laboratory models. Anticonvulsant effects of rTMS depend on severalparameters among which radiation frequency is the most important one. In this study, thetherapeutic impacts of 1 and 2 Hz rTMS on convulsing parameters in epileptic model ofelectrical kindling stimulation of the perforant path were investigated.Materials and Methods: In this experimental study 21 rats were randomly divided intothree groups, namely ‘1 Hz treatment group’ and ‘2 Hz treatment group’ and ‘kindlinggroup’. The kindling group only received kindling stimulations for seven days. One Hzand 2 Hz frequency treatment groups received maximally 5 min rTMS after termination ofkindling stimulation per day for a week. Stimulation and stability electrodes had beenplaced, in turn, on perforant path and dentate gyrus. For quantifying the duration of thesubsequent discharge waves, two-way ANOVA test and Bonferroni post-test wereemployed. In addition, for quantifying the convulsive behaviors, Kruskal-Wallis and theMann-Whitney U tests were used.Results: The results showed that 1 Hz and 2 Hz frequency rTMS have considerableinhibitory impact on the development of convulsive phases. Anticonvulsive effect wasobserved from the first day after rTMS was undertaken. In addition, the animals did notshow fourth and fifth convulsive stages, and a significant reduction was evident in theirrecorded peak discharge waves compared with kindle group.Conclusion: Low frequency rTMS possesses significant anticonvulsive effects whichdepend upon sTMS stimulation frequency.

Introduction: Considering high prevalence of epileptic disease and considering that 40 percent of epileptic patients are resistant to drug therapy, it needs more researches to find new therapeutic ways. LFS is among the new methods for epilepsy treatments. One possible mechanism involved in the anticonvulsant effect of LFS is increased adenosine. Therefore, in this study the role of adenosine production from ATP by ectonucleotidase enzyme pathway in exerting the anticonvulsant effects of LFS were evaluated.Methods: Animals were kindled by electrical stimulation of perforant path in a rapid kindling manner (12 stimulation per day). One group of animals received LFS after kindling stimulation. In one another group, AOPCP a blocker of ectonucleotidase inhibitor was micro injected (50 micro molar) intra cerebro ventricular each day before LFS stimulation. Some group of animals were also received AOPCP (50 and 100 micro molar) but were not applied to LFS. Seizure behavior and electrophysiological parameters (including ADD and field potential) were recorded. Results: Like previous investigations, application of LFS, decreased all seizure parameters significantly. Microinjection of AOPCP had no significant effect on anticonvulsant actions of LFS. However microinjection of AOPCP at doses of 100 micro molar in animals that received just kindling stimulations, increased the seizure parameters significantly. Conclusion: The results show that adenosine production via ectonucleotidase enzyme pathway may has no role in anticonvulsant effects of LFS; however endogenous adenosine produced through this pathway has an important role in kindling development.

Background and Purpose: Application of low-frequency stimulation (LFS) induces anticonvulsant effects. In this study, the effect of changes in LFS frequencies on its anticonvulsant effects in kindling model of epilepsy was investigated by determining the behavioral and ultrastructural changes.Methods and Materials: In this experimental study, 45 Wistar rats weighing 250-280 g were used. For induction of kindled seizures, stimulating and recording electrodes were implanted in perforant path and dentate gyrus respectively. Animals were stimulated in a rapid kindling manner. Different groups of animals received LFS at different frequencies (0.5, 1 and 5 Hz) following kindling stimulations and their effects on kindling rate were determined using behavioral and electrophysiological studies.After stimulating the animals for 7 days, they were killed and their dentate gyri were sampled for ultrastructural studies under electron microscopy. For data analysis, one-way and two-way ANOVA, LSD, Kruskal Wallis and Mann Whitney U were used in Statistica 2.Results: Different LFS frequencies had a significant inhibitory effect on kindling rate and decreased after-discharge duration and the number of stimulations to achieve stage 4 and 5 seizures significantly. In addition, application of LFS prevented the increase in the post-synaptic density and induction of concave synaptic vesicles following kindling. There was not any significant change between anticonvulsant effects of LFS at different frequencies.Conclusion: Obtained results show that LFS application can prevent the neuronal hyper-excitability by preventing the ultrastructural changes during kindling, and can exert its anticonvulsant effects.

Introduction: Previous studies have shown that low frequency stimulation (LFS) has an inhibitory effect on kindling acquisition. However, the mechanism of this effect has not been completely determined. In the present study, the effect of LFS of the perforant path on seizures induced by rapid perforant path kindling was investigated.Methods: Animals were kindled by electrical stimulation of perforant path, One group of animals (n=6) received LFS (0.1 ms pulses at 1 Hz, 200 pulse, and 50-150mA) after termination of each kindling stimulations. In control groups, animals received only kindling stimulations (n=8) or LFS (n=4). Basal field potential recording and paired pulse stimulations were done every day, before kindling stimulations.Results: Application of LFS significantly retarded the kindling acquisition and increased the number of stimulations to achieve different seizure stages [F(4,60)= 10.9, P<0.0001]. LFS also prevented increment of slope of field excitatory postsynaptic potentials and population spike amplitude during kindling (P<0.001) (There was 88.6±1.7% increment in fEPSP and 94±2.3% increment in PS in kindled group and 3.5±05% increment in fEPSP and 12.3±0.1% decrease in PS in kindled+LFS group). In addition, LFS significantly prevented the marked increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression induced by kindling (P<0.01).Conclusion: According to obtained results, it may be suggested that LFS of perforant path has a significant antiepileptogenic effect on perforant path kindled seizures through inhibition of synaptic transmission in dentate gyrus. Meanwhile, LFS prevents compensatory increase in the paired pulse depression during kindling acquisition.

Introduction: In the present study, the impotency of galanin receptors 2 (GalR2) in the inhibitory effect of LFS on perforant path kindling acquisition was investigated. Methods: Animals were kindled by perforant path stimulation in a rapid kindling manner (6 stimulations per day). LFS (0.1 ms pulses at 1 Hz, 600 pulses, and 50-150 µA) was applied immediately after termination each kindling stimulation. M871 (1.0 mM per site) a selective galanin receptor type 2 receptor (GalR2) antagonist, were daily microinjected into the dentate gyrus before starting the stimulation protocol and behavioral seizure stages and afterdischarge durations were recorded. The expression of GalR2 in the dentate gyrus of different groups of animals was also compared using semi-quantitative RT-PCR. Results: Intra-dentate gyrus microinjection of M871 significantly prevents the inhibitory effect of LFS on kindling acquisition. Semi-quantitative RT-PCR showed that after kindling acquisition, the GalR2 mRNA level decreased in the dentate gyrus but application of LFS prevented this decrease. Conclusion: According to these data it may be suggested that activation of galanin receptors by endogenous galanin has an important role in mediating part of the inhibitory effects of LFS on perforant path kindled seizures. This role is mainly exerted through GalR1 during focal- and through GalR2 during generalized-kindled seizures.

Background and Purpose: Previous studies have not properly clarified the role of A2A adenosine receptors in convulsions induced by kindling. In the present study, the role of these receptors in convulsions induced perforant path kindling has been investigated by blocking these receptors (with specific antagonists).Methods and Materials: This experimental study was conducted on 24 rats which were randomly divided into four groups of six. They were kindled by electric stimulation of the perforant path. In two groups, before each kindling stimulation, antagonists of A2A adenosine receptors (ZM 241385) (500 and 200 mM) was injected to the lateral ventricle of the rats. Control animals were given only the electric stimulations. In the fourth group (sham), the solvent of the abovementioned drug was injected to the lateral ventricle before kindling stimulations. The obtained data were analyzed using two-way ANOVA and Tukey tests.Results: Injecting the antagonists of A2A adenosine receptors (ZM 241385) (500 mM) to the lateral ventricle of the rats postponed the process of kindling. Two-way ANOVA indicated that number of stimulations required to reach the convulsive stages were significantly increased (P<o.oo1, F(4, 40) = 47). Also, compared with the sham group which received the solvent of the drug, a significant reduction was observed in the duration of depletion waves following accumulation (P<0.05, F(6, 60) = 2.5) in this group.Conclusion: According to the findings, injecting the antagonists of A2A adenosine receptors produces a significant anticonvulsant effect on the convulsions induced by perforant path kindling, and that this effect functions through controlling the effect of endogenic adenosine on A2A adenosine receptors.