جستجوی مقالات مرتبط با کلیدواژه « کیندلینگ » در نشریات گروه « پزشکی »

Sodium valproate is one of the most common antiepileptic drugs used in the first line of treatment for epilepsy, bipolar disorder, mood disorders, and more recently, as an anticancer drug. The occurrence of seizures and the use of Sodium valproate both have sexual and hormonal side effects and ultimately cause infertility in males. In previous studies, the definitive effects of seizures and valproate have not been investigated. This study investigated how sex hormone levels change in male rats due to sodium valproate consumption in the pentylenetetrazole kindling model. 

Twenty-four male rats were divided into three groups (n = 8). Intraperitoneal injections were every 48 hours, and the groups included: control (saline), PTZ + Saline, PTZ + VPA. The priority of injecting drugs in the groups was first saline, VPA (300 mg/kg), and finally, PTZ (mg/kg), and injections were performed every 48 hours. Hormone testing was performed at the end of kindling and at the 15th injection. 

Following the kindling of male rats, a significant decrease in testosterone and a significant increase in progesterone, as well as an increase in estradiol, were observed. VPA injection in male Kindle rats significantly reduced testosterone (P <0.05) (P <0.001) compared to saline and PTZ + Saline groups, respectively. Estradiol levels in the Kindle group receiving VPA increased significantly compared to the saline group (P <0.05). 

The process of seizures disrupts sex hormones. Also the use of valproate aggravates these hormonal and sexual disorders.

Background and Objectives:

 Nowadays, the application of Low Frequency Stimulations (LFS) has been considered as an alternative treatment in drug-resistant epileptic patients. So, the aim of this study was to determine the co-administration effects of LFS and carbamazepine (CBZ) during epileptogenesis in dorsal hippocampus using electrical Kindling method on seizure scales in adult male rats.

In this experimental study, 56 adult male wistar rats were randomly divided into 8 equal groups including: Kindled (KND), KLFS, MCK, CBZ20K, CBZ40K, CBZ20KLFS, CBZ40KLFS, and MCKLFS. Animals in the Kindled group received daily stimulation of kindling. In the KLFS group, LFS were applied daily after the termination of kindling stimulation. In the MCK group, before induction of kindling stimulation, the amount of 0.2 ml of %0.5 methyl cellulose was injected, and CBZ20K and CBZ40K groups received CBZ20 and 40mg / kg. In the CBZ20KLFS, CBZ40KLFS, and MCKLFS groups in addition to receiving drug or solvent, LFS was applied at the end of kindling stimulation. Animal behavioral seizure scales (seizure severity, afterdischarge duration and seizure duration) were recorded. Finally, data were analyzed using one-way ANOVA followed by Tukey’s post hoc test.

The results showed that the combination therapy of LFS and the effective and ineffective amounts of CBZ significantly reduced the seizure scales in CBZ20KLFS and CBZ40KLFS groups compared with the other experimental groups (p=0.035).

It seems that combination therapy of CBZ and LFS is an appropriate method to reduce seizure scales during kindling in rats.

Epilepsy is a chronic neurological disorder that requires long treatment with less side effects. Therefore, this study aimed to determine the effect of sodium valproate and electrical stimulation of the brain with low frequency (LFS) on the motor activity of male rat during hippocampus rapid kindling. In this experimental study, 56 male adult rats were randomly divided to 8 groups: control, sham operation, saline-kindled and drug-kindled groups which received saline or drug 15 minutes before kindling stimulations and saline-kindled-LFS or drug-kindled-LFS group which received saline or drug 15 minutes before kindling stimulations and LFS after termination of kindling stimulations. Then animals motor activity was assessed on the 6th day by open field test and data were analyzed by one-way ANOVA and Tukey's post-test. The open field results showed a significant increase in the number of motions (p =0.007) in the kindled group compared to the sham group. But these parameters showed no difference in saline-kindled-LFS group, drug-kindled and drug-kindled-LFS groups compared with the sham group (p˃0.05). It seems administration of sodium valproate and application of low-frequency electrical to hippocampus region can attenuate the kindling-induced hyperactivity in adult male rat. Key words: Sodium valproate, Low frequency electrical stimulation, Open field, Kindling, Rat   Funding: This research was funded by Shahid Chamran University of Ahvaz. Conflict of interest: None declared. Ethical approval: The Ethical Committee of Shahid Chamran University of Ahvaz approved the study (EE/97.3.24.49755/scu.ac.ir).   How to cite this article: Zalkhani R, Moazedi AA, Ghotbeddin Z, Pourmahdi Borujeni M. The Effect of Sodium Valproate and Low Frequency Electrical Stimulation on Motor Activity During Rapid Kindling of Hippocampal CA1 Region in Adult Male Rat: An Experimental Study. J Rafsanjan Univ Med Sci 2019; 18 (1): 43-54. [Farsi]

Epilepsy is the third world neurological disorder. Epileptic focus causes motor impairment by sending projections to different areas of the brain such as areas which are related to movement control. Regarding the inhibitory effect of low-frequency electrical stimulation (LFS) on seizure wave's transmission, this study aimed at examining the effect of LFS during the epileptogenesis of dorsal hippocampal on balance and locomotor activity in adult male rats using the kindling method. Fifty rats were randomly divided into 5 groups: Control, Sham, Kindled, LFS and KLFS. Animals in the kindled group were stimulated rapidly by daily stimulation of dorsal hippocampus (1 ms pulse duration at 50Hz for 3 seconds). Animals in the sham and control groups did not receive any stimulation. In the LFS groups, four LFS packages at a frequency of 1 Hz were applied daily. At the end of stimulation, motor activity and balance were assessed by open-field and rotarod tests. Frequency of rearing and grooming in the Kindled group significantly increased compared to the control group (P<0.05). Balance in the Kindled group was significantly decreased (P<0.05). LFS induction during hippocampal kindling did not show any significant difference in any of the mentioned parameters with the control group. In summary, applying low-frequency electrical stimulation during hippocampal kindling can reduce the motor activity and improve balance.

Emotional disorders are prevalent in many epileptic patients. So, in this research, we have studied the efficacy of two treatment methods of seizure on anxiety-like behavior during kindling in adult male rat. 42 male rats were randomly divided into 6 groups: Control, Sham operation, saline-kindled and drug-kindled groups which have received saline or drug 15 minutes before kindling stimulations, and saline-kindled-LFS or drug-kindled-LFS group which have received saline or drug 15 minutes before kindling stimulations and LFS applied after termination of kindling stimulations. Anxiety-like behavior was assessed on the 6th day by using elevated plus maze and open field apparatus.
Findings: kindling significantly increased open arms (OAs) entries percentage, OAs exploration percentage, increasing jumping from elevated plus maze (p<0.001) and rearing frequency in open field apparatus (p<0.05) compared to the sham group. Sodium valproate increased OAs entries percentage and OAs exploration percentage in drug-kindled group compared to sham group (p<0.001). But, there wasn’t any significant difference in jumping from elevated plus maze and rearing in open field compared to sham group. Also, there was no significant change in these parameters in Saline-kindled-LFS, drug-kindled and drug–kindled-LFS groups. Sodium valproate and LFS, as two therapies controlling epilepsy, decrease anxiety induced by kindling stimulation

There are many evidence to indicate the role of serotoninergic system and serotoninergic activation in seizure attacks. Given the role of serotonin 5-HT1A receptors in synaptic activity and seizure models, and, the similarity of the mechanisms involved in causing seizures and long term potentiation (LTP), the purpose of this study was to investigate the role of this receptor in pentylenetetrazol (PTZ)-induced synaptic strengthening.
24 Male Wistar rats (n=20, 220-320 g) were divided into 6 groups; Group1 (control); without any interference after surgery stereotoxic placement of stimulation electrode, Local Field Potential (LFP) was recorded for 20min .Then; the LTP was induced with tetanic stimulation. Group2: All experimental procedures were similar to the group 1, the difference was that the one-month period before the surgery, the animals kindled with PTZ injection. Groups 3-5: All experimental procedures were similar to the group 2, the difference was that the serotonin receptor antagonist (WAY-100635; at a concentration 12.5, 25 and 50nM) was injected intraventricularly. Group 6 received WAY-100635 only.
The results showed that groups 1 and 2 were different responded from one another after LTP induction of LTP with tetanic pulse (p The results showed that 5HT1A receptor antagonist attenuated the induction of LTP in kindled animals. It seems that serotonin agonist that enhances LTP induction and thus may be useful in enhancing learning and memory in people with epilepsy

Considering the role of glial cells in synaptic transmission, regulation of neurotransmitter concentration in synaptic cleft, K buffering, and releasing the gliotransmitters, the purpose of this study is to investigate the effect of glial cells inhibition on the progression of seizures induced by chemical kindling in rats.
In chemical kindling, animals received Pentylenetetrazol, 35 mg/kg each 48 hours, intraperitoneally and five different stages of seizure were appeared gradually and seizure parameters including maximum seizure stage (SS), stage 4 latency (S4L), stage 4&5 duration (S5D), and seizure duration (SD) were measured during 20 min after PTZ injection. Then seizure parameters were evaluated in animals treated with intracerebroventricular (icv) administration of Fluorocitrate (as a glial cells inhibitor), injected 30 min before PTZ, and compared with PTZ treated animals.
Results showed that glial cells inhibition with ICV injection of Fluorocitrate decreased SS, S5D, and SD and increased S4L significantly (P

Epilepsy is one of the most common neurological disorders that affect on many aspects of people's lives. Multiple treatment methods were used for epileptic patients. Recently, treatment effects of medicinal plants on epilepsy have been investigated. In attention to components of Origanum vulgare and the usage of it in traditional medicine as an anti-convulsion herb, this study was carried out to assess the anti-convulsive effects of Origanumvulgare extract on chemical kindling model of epilepsy.
The present experimental study has been carried out on 40 male mice that they have been chosen randomly and divided into 5 equal experimental groups, including one control group received only Pentylenetetrazole (PTZ), one sham group received distilled water and three experimental groups that 30 minutes before PTZ injection received equeous extract of Origanumvulgare in doses of 400, 600 and 800 mg/kg of body weight via gavage tube. Chemical kindling was performed on all of them for 12 times intraperitoneal injection of 45 mg/kg of body weight of PTZ at every 48 hours. Data analyses were carried out by one way ANOVA and Tukey post-hoc test.
Data analysis showed that administration of Origanum vulgare extract has a significant effect on chemical kindling. It decreased the progress of seizure stages significantly (P˂0.05) and increased latency time for onset of seizure considerably (P˂0.05), but it had no significant effect on seizure duration.
The results obtained from the present study showed aqueous extract of Origanum vulgare plant had anti convulsant effect on chemical kindling. Thus, it may be useful for epilepsy treatment.

Kindling can increase anxiety-like behavior in rodents. Oxidative stress has an important role in arousing anxiety. It is known that Matricaria Recutita has an antioxidant effect. Thus, the present study aimed at assessing the effects of this plant’s extract. on anxiety-like behavior induced by kindling in rats.
In this experimental study, 40 male Wistar Albino rats (wt:200-250 g) were randomly divided into 4 equal groups; namely control (intact), kindling, diazepam (2 mg/kg), and aqueous extract of Matricaria Recutita (30 mg/kg) intrapertoneally. Kindling was done by a sub-convulsive dose of pentylenetetrazole (PTZ; 40 mg/kg, i.p.) in the remainder . groups. Kindling parameters in all these animals were evaluated by a plus elevated maze. The percent of time spent in the open arms of maze (OAT %) and percent of entries in the open arms (OAE %) were accounted for anxiety evaluation. Increase in OAT % and OAE % indicated an anxiolytic effect. Finally,the obtained data was analyzed by means of Any-Maze software and P Kindling significantly (P The results of the present study showed that Matricaria Recutita was able to improve elevated levels of anxiety in kindled rats. Therefore, further works are needed to elucidate the extent and mechanism of these effects.

Background and Low frequency stimulation (LFS) has anticonvulsant effect. However, its mechanism of action has not been completely determined. In the present study the effect of LFS on evoked inhibitory post synaptic GABAergic currents (eIPSC) is investigated in CA1 pyramidal neurons of the hippocampus in kindled rats.
In this experimental study animals were kindled through electrical stimulation of amygdala. 24 hours following fully kindling achievement in 20 Wistar rats, the effect of LFS on eIPSCs was assessed in hippocampal slices.
Obtained results showed that application of LFS at 200 pulses and at the intensity of 1.5 threshold, increased the amplitude and decay time constant of eIPSCs in both control and kindled rats. When 200 pulses of LFS were administered with an intensity equal to threshold, only eIPSC amplitude was increased in both control and kindled groups significantly (P Results of the present study showed that LFS application increased eIPSCs parameters in a pulse number and intensity dependent manner. This increment can be considered as a possible anticonvulsant mechanism of LFS.

Epilepsy, as a plastic change lead to hyperexcitability and structural change. Kindling is the process of repetitive subconvulsive electrical or chemical stimulation induced synaptic and circuit alterations. Lateral hypothalamus (LH) contains the main constellation of orexinergic neurons involved in sleep and waking and even excitability with high numbers of receptors in hippocampus. Thus, we investigate the effect of LH inactivation on kindling development and kindling induced hippocampal neuronal population.
Pentylenetetrazol (PTZ; 45 mg/kg) was used to induce chemical kindling every 48 h up to 13 injections, intraperitoneally. Three consecutive 4 or 5 seizure stages were criteria for kindling. Lidocaine (2%) was injected stereotaxically into right LH, 0.5 h prior to PTZ administration. Nissl staining was used to demonstrate neuronal population survival in CA3 and hilar regions of hippocampus.
LH inactivation prevented PTZ kindling development. Although kindling increased neuronal dispersion in CA3 and hilar regions, LH inactivation was unable to reduce the dispersion. Moreover, kindling did not affect neuronal survival in CA3 and hilus, qualitatively.
It is concluded that kindling induced structural changes is to some extent independent of kindling development and it is not prevented by kindling inhibition through LH inactivation.

Harmaline is one of the beta carboline of Peganumharmal. Harmaline and other carbolines are inverse agonists for benzodiazepine receptors with many inverse effects of benzodiazepines including anxiety and CNS excitement. The aim of this study is the effect of harmaline on seizure- induced by amygdala kindling in rats.

in this experimental study, eighteen kindled wistar rats (3 groups) were injected intraperitoneally with saline and on the following day, with Harmaline (50, 25, 12.5 mg/kg). After discharge duration (ADD), stage 5 duration (S5D), stage 2 latency (S2L) and stage 4 latency (S4L) of seizures were recorded and compared with those of the saline groups.

Harmaline reduced S2L and S4L in 3 groups, and increased ADD and S5D not significantly but increased ADD only in group 15 mg/kg significantly (P<0.05).

The obtained results revealed that harmaline has proconvulsant effect and maybe via stimulation of excitatory pathways or blocking of inhibitory pathways, or any other excitatory mechanisms cause increase in neuron activity and firing.

Background and Minocycline has got the anti-inflammatory and neuroprotective effects. Considering the interaction between cell death and seizure, and on the other hand, Kindling which increases expression NMDA receptors in brain, the aim of this study is to investigate the effect of minocycline on gene expression of NMDA receptor in hippocampus and piriform brain areas on amygdale kindling acquisition in rats. In this experimental study, three animal groups of 24 Wistar rats received kindling stimulations (twice daily within 6 hours intervals) after being stereotaxic operated and taking one week recovery period. In first Group (n=8) animals did not received daily kindling stimulations. Animals of the second and the third Groups (n=8) respectively had been injected by saline (1ml/kg) and minocycline (25 mg/kg), 60 minutes before receiving kindling stimulations. Two hours after last stimulation animal’s brains were removed and the changes of NR2A gene subunit of NMDA receptor in the hippocampus and piriform cortex were measured and compared relative to the control group. Datawere analyzed using ANOVA and Tukey post hoc tests at significant level of P<0/05. Intraperitoneal administration of minocycline before kindling stimulations prevented an increase in the mRNA of NR2A subunit of NMDA receptor in hippocampus and piriform cortex of amygdala kindling. The results of this study have shown that minocycline administration before electrical stimulation has anticonvulsant effects which are applied through a decrease in expression of NMDA receptors.

Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, exists as two isoforms, cyclooxygenase-1 and cyclooxygenase-2. Previous studies have shown the protective effect of cyclooxygenase enzyme in the development of convulsion. However, the involvement of Cyclooxygenase-1 in the pathogenesis of epilepsy has not well known. The present study was designed to explore whether indomethacin (a nonspecific COX inhibitor) can affect pentylenetetrazole (PTZ)-induced kindling in rats. Kindling, as a chronic model of epilepsy, was inducted by the intraperitoneal injection of PTZ (37.5 mg/kg) every 48 hours (13 times) in all groups. In the pre-treatment groups, intraperitoneal injection of indomethacin (2.5, 5, 10 mg/kg) was done 20 min before each PTZ injection. In sham group, tween (20%) was used as a solvent. Repeated injections of PTZ after 13 sessions significantly induced the kindling in the control group. In pre-treatment groups, indomethacin (2.5, 5, 10 mg/kg) significantly decreased PTZ-induced mean kindling scores. The finding that the indomethacin can partially reverse the kindling mean scores in rat indicates the involvement of cycloogygenase-1 isoform. It seems that cycloogygenase-1 inhibitors could be a useful choice for the treatment of epilepsy.

Minocycline has anticonvulsant effects. Since some antiepileptic drugs increase the neurotransmitter GABA in the brain, the aim of this study is the effect of minocycline on gene expression of GABAA receptor in hippocampus and piriform brain areas on amygdale kindling acquisition in rat. In this experimental study, three group (24 Wistar rats), after stereotaxic surgery and 1 week recovery period, received kindling stimulations(twice daily at 6 hours interval). Group 1(n=8) did not receive daily kindling stimulations. Group 2 (n=8) received intraperitoneal saline (1ml/kg) and Group 3 (n=8) received intraperitoeneal minocycline (25 mg/kg) 60 min before kindling stimulation and respectively. Two hours after the last stimulation, animals’ brains were removed and the changes of gene expression by γ2 subunit of GABAAreceptor in the hippocampus and piriform cortex were measured and compared with the control group. Data was analyzed using one-way ANOVA and Tukey post hoc tests (P<0/05). In Group 3 intraperitoneal administration of minocycline for 10 days reduced cumulative ADD significantly reduced in comparison with the control group (Group 2) (P<0.001); also, it increased significantly the delay time of stage 4 (p<0.01) and stage 5 (p<0.001) of the seizures. In addition, the injection of minocycline before kindling stimulations removed the electrical stimulation induced an increase in mRNA of γ2 subunit of GABAA receptor in hippocampus and piriform cortex of amygdale kindling. The results of this study showed that minocycline administration before electrical stimulation acts as an anticonvulsant, and this effect occurs via reducing GABAA receptors.

Epilepsy is one of the common neurological disorders. Today, there are many drugs for treatment of this disease, which most of these chemical drugs have harmful effects on patients’ health. The aim of the present study was to investigate the effect of hydroalcoholic extract of dill (Anethum graveolens) seeds on the pentylenetetrazole-induced chemical kindling. This experimental study was conducted on 50balb/c male mice weighting 25-35g. Mice were divided into five groups of 10. Three experimental groups received hydroalcoholic extract of dill seeds by three concentrations of 150, 300 and 600mg/kg of the animals’ body weight. Positive control group received diazepam (3mg/kg) instead of the extract. Likewise, negative control groups received sterile normal saline (6mg/kg) instead of the extract. In order to exactly compare the different concentrations of the drug and extract on the times after injection on the paroxysm values, ANOVA and supplementary Tukey test as well as SPSS 18 software were used. At doses of 150 and 300mg/kg, dill had desirable inhibitory effect on the epileptic behavior of animals at different days (p<0.01). Moreover, at dose of 600mg/kg, it favorably inhibited the mice’ epileptic movements (p<0.01). The hydroalcoholic extract of dill seeds has antiepileptic (anti-seizure) effect at dose of 600mg/kg on mice.

Background and Minocycline is an antibiotic and anti-inflammatory drug. In addition, its neuroprotective effects have been shown. Since there is interaction between cell death and seizure, the aim of this study is examination of the role of minocycline on amygdala-kindled seizures in rat.Methods and materials: In this experimental study, three groups of animals (18 rats), after stereotaxic surgery and 1-week recovery period, received twice daily kindling stimulations. In fully kindled animals of groups 1-3, minocycline was injected intraperitoneally in doses 12.5 (n = 7), 25 (n = 5) and 50 (n = 6) mg/kg, respectively, 60 minutes before stimulation. Afterdischarge duration (ADD), stage 4 latency (S4L), Stage 5 Duration (S5D) and Seizure Duration (SD) were recorded and compared with related control groups (the same animals that had received saline 1 day before). A p-value of less than 0.05 was considered to represent a significant difference. In fully kindled animals who had received minocycline (50 and 25 mg/kg), ADD decreased significantly. When minocycline was delivered, S5D decreased 38.3% (p < 0.001), 34% (p<0.05), and 100% (p<0.001) in 12.5, 25, and 50 mg/kg group animals, respectively. S4L and SD parameters respectively increased and decreased significantly only in group 50 mg/kg. According to the obtained results, it may be concluded that in fully kindled rats, application of minocycline has anticonvulsant effect on kindling model of epilepsy.

Background and Ethanol is known as anticonvulsant and proconvulsant but sometimes has no effect on seizure. There is no report about the role of ethanol on the anticonvulsant effect of Valproic acid (VPA). In this study, we explore the effect of ethanol on the anticonvulsant effect of VPA. Methods and Materials: In this experimental study, eight groups of mice (25-30 gr) were injected pentylenetetrazol (PTZ) (37 mg/kg; ip) every other day (3 times a week). Groups receiving ethanol (0.5 and 1 g/kg; 7 and 21 continuous days; everyday; ip), PTZ was injected 30 minutes after ethanol. In Valproic acid+ethanol, Valproic acid (100 mg/kg) was injected 5 minutes before ethanol (1 g/kg). Immediately after PTZ injection, seizure stages were recorded for 20 min. Seizure stage-4 duration (S4D), seizure stage-4 latency (S4L) and seizure stage 1 latency (S1L) were recorded from each mouse after PTZ injection, and data were compared with control groups. The basis of all decisions was a significant level of P<0.05. Data analysis was done in Statistica 5.5. Pretreatment of animals with ethanol (1 g/kg for 7 days) decreased cumulative (c) S4D (%31.8 PTZ+Saline); and with ethanol (1 g/kg for 21 days) decreased cS4D (%48.3 PTZ+Saline) (P<0.001), but increased cS4L (%112.6 PTZ+Saline) and cSL (%116.8 PTZ+Saline) significantly (P<0.001). Pretreatment of animals with VPA (100 mg/kg) significantly decreased cumulative (c) S4D (%39 PTZ+Saline) (P<0.001), and significantly increased cS4L (%216.8 PTZ+Saline) and cS1L (%149 PTZ+Saline) (P<0.001). Intraperitoneal injection of VPA+ethanol significantly decreased cS4D (%56.1 relative to PTZ+VPA and %46.1 relative to PTZ+Eth 1 (7)) (P<0.001); it also increased cS4L (%233.9 relative to PTZ+VPA and %450 relative to PTZ+Eth1 (7)) (P<0.001), but had no effect on cS1L as compared to VPA and ethanol (1 g/kg; 7 days). The results indicated that ethanol (1 g/kg) functions not only as an anticonvulsant but its simultaneous injection (7 continuous days) also enhances the anticonvulsant effects of valproic acid.

Background and 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. 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). 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.

Application of low-frequency stimulation (LFS) is a new method for treatment of drug resistant epileptic patients. Previous studies demonstrated that activation of receptors coupled to Gi proteins is one of the mechanisms of the anticonvulsant effect of LFS. Thus, in this study, alterations in the expression of RGS4 and RGS10 proteins, as negative regulators of Gi proteins, were investigated.

Animals were kindled by perforant path stimulation in a rapid kindling manner (12 stimulation per day, 1 ms pulse duration at 50 Hz). LFS (8 stimulation per day, 0.1 ms pulse duration at 1 Hz, 200 pulses) was applied to the perforant path 5 minute after the termination of kindling stimulations. After electrophysiological recordings for 6 days, the dentate gyrus of the animals was removed and RGS4 and RGS10 protein expression was studied by western blotting technique.

Application of LFS significantly retarded kindling acquisition and increased the number of stimulations to achieve different stages of seizure. LFS also significantly reduced after discharge duration. In addition, application of LFS after kindling stimulation reduced the expression of RGS4 and RGS10 proteins.

Results of the present study showed that LFS has anticonvulsant effects on the perforant path kindling. Application of LFS following kindling stimulation reduced the expression of RGS4 and RGS10 proteins. Reduction of the expression of these proteins results in the longer activation of signaling pathways of Gi proteins, which may be responsible for LFS anticonvulsant effects.