Penicillin-induced Epileptiform Activity In Rats Research Articles

Effects of Sinapic Acid on Penicillin-Induced Epileptiform Activity in Rats

Effects of Sinapic Acid on Penicillin-Induced Epileptiform Activity in Rats

The CB1 cannabinoid receptors involvement in anti-epileptic effect of safranal on penicillin-induced epileptiform activity in rats.

Neuroprotective effects for natural products are supported by several studies. In this regard, safranal, a constitute of saffron, has the potential to exert beneficial effects in neuro-logical disorders such as Parkinson's disease, epilepsy, stroke, multiple sclerosis and Alzheimer's disease. Here, we investigated the effect of safranal on penicillin-induced epileptiform activity. Also, the effects of intracerebroventricular (ICV) microinjection of AM251 as a CB1-cannabinoid receptors antagonist to clarify the possible mechanism of safranal were evaluated. Epileptiform activity was induced by intra-cortical administration of penicillin (300 IU, 1.50 μL) in urethane-anesthetized rats. Electrocorticographic recordings were used to analyze the frequency and amplitude of spike waves. Intraperitoneal injections of safranal at doses of 1.00 and 4.00 mg kg-1 significantly reduced both the number and amplitude of spike waves. The ICV microinjection of AM251 (0.50 μg 2.00 μL-1) significantly increased the frequency and amplitude of spike waves. In addition, the anti-epileptic effect induced by administration of safranal at a dose of 4.00 mg kg-1 was partially prevented by ICV microinjection of 0.50 μg 2.00 μL-1 of AM251. The results showed anti-epileptiform activities for safranal. Central CB1 cannabinergic receptors might be involved in the anti-epileptiform activity of safranal.

Effect of adropin on seizure activity in rats with penicillin-induced epilepsy

BackgroundEpilepsy is a nervous system disease that affects millions of individuals worldwide, and up to 25% of patients have seizures that are resistant to antiepileptic drugs. Therefore, there is a need for the discovery of tolerable, effective antiepileptic agents. This study was aimed to electrophysiologically investigate the effects of the peptide hormone adropin, which was discovered in recent years and whose expression was determined in many organs, on penicillin-induced epileptiform activity in rats. MethodsForty 16–18 weeks old 280–300 g female Wistar albino rats were divided into 5 groups, 8 in each group. 250 min of ECoG recordings were taken from the first group only under anesthesia. Penicillin was given to the second group, L-arginine to the third group, adropin to the fourth group, and these three substances to the fifth group, and records were taken for 250 min and statistically evaluated. ResultsMeasurements were made as spike frequency, amplitude values, spike percent change, amplitude percent change. It was determined that the substances given on penicillin-induced acute epilepsy reduced both the number and severity of epileptic seizures. The lowest values were obtained from the L-arginine group, second from the mixture group, and third from the adropin group. ConclusionsAlthough the hormone adropin was not as effective as L-arginine on seizure activity, it can be said that it has a positive effect in terms of antiepileptic activity.

Esculetin alleviates pentylenetetrazole-induced seizures, cognitive impairment and pro-inflammatory cytokines and suppresses penicillin-induced epileptiform activity in rats

AimsTo investigate the effects of different doses of esculetin on epileptiform activity, behavioral seizures, memory impairment, and cortical and hippocampal NF-κB, as a mediator of pro-inflammatory gene induction, and pro-inflammatory cytokines in penicillin- and pentylenetetrazole(PTZ)-induced seizure models in rats. Main methodsDifferent doses of esculetin (5, 10, and 20 mg/kg), and diazepam (5 mg/kg) as a positive control, were tested in penicillin- and pentylenetetrazole(PTZ)-induced seizure models. In the PTZ model, cognitive function, behavioral seizures, and cortical and hippocampal pro-inflammatory biomarkers and survival factor was evaluated. In the penicillin model, the frequency and amplitude of electrophysiological epileptiform activity were assessed. Key findingsIn the PTZ model, the 10 mg/kg esculetin displayed anticonvulsant effects by extending onset-times of myoclonic-jerk and generalized tonic-clonic seizure, and by diminishing seizure severity and duration of generalized tonic-clonic seizure. It also ameliorated PTZ-induced cognitive impairment, and cortical and hippocampal activin-A, IL-1β, IL-6 and NF-κB levels. In the penicillin model, the 10 mg/kg esculetin decreased the frequency of spikes without changing the amplitude of spikes. As a positive-control, diazepam reversed all changes induced by both PTZ and penicillin. SignificanceEsculetin exhibits anticonvulsant and memory-improving effects by alleviating the behavioral and electrophysiological characteristics of epileptic seizures. Additionally, esculetin exerts anti-neuroinflammatory actions in the PTZ-induced seizures model. Thus, esculetin may be a multi-targeted promising agent with anticonvulsant and anti-neuroinflammatory effects in the treatment of epilepsy.

Acute treatment with dexketoprofen reduces penicillin induced epileptiform activity in wistar albino rats (dexketoprofen in penicillin induced seizure model)

AimDexketoprofen trometamol is one of the most commonly used anti-inflammatory analgesic agents for pain control. This study aims to investigate the effect of dexketoprofen on penicillin-induced epileptiform activity in rats. MethodIn this study, 28 male Wistar rats weighing 220–240 g were used. Tripolar electrodes were implanted under urethane anesthesia. Epileptiform activity was induced by micro-injection of 500 units (IU) penicillin into the rats’ left somatomotor cortex. Dexketoprofen (5, 25, and 50 mg/kg) was administrated intraperitoneally after 30 min of penicillin injection. Epileptiform activity was evaluated by electrocorticography (ECoG). ResultsThe low dose of dexketoprofen administration (5 mg/kg) reduced the mean spike frequency of epileptiform activity 60 min after its injection. However, 25 and 50 mg/kg dexketoprofen significantly reduced the mean spike frequency 30 min after the dexketoprofen injection compared to the control group (p < 0.05). The amplitudes of epileptiform discharges in all groups were unaffected (p > 0.05). ConclusionThis study revealed that dexketoprofen had a significant anti-seizure effect when applied at 5 mg/kg, 25 mg/kg, and 50 mg/kg (especially at 25 and 50 mg/kg), in the penicillin-induced seizure model. The obtained data revealed that dexketoprofen might play an essential role against epileptic seizures.

Hemopressin increases penicillin-induced epileptiform activity in rats.

Hemopressin(Hp) is the first peptide ligand described for the CB1 cannabinoid receptor. Therefore, we aimed to investigate the effect of hemopressin on pencillin-induced epileptiform activity by using electrophysiological recording (ECoG) technique. Male Wistar rats were anesthetized with urethane (1.25 g/kg), and epileptiform activity was induced by intracortical injection of penicillin (500 IU). Animals were randomly divided into eight groups. Subsequently, the rats were administered with saline or hemopressin as follows: saline control group (Group I: 2 μl/i.c.v/saline), hemopressin groups (Group II: 0.025 μg/i.c.v; Group III: 0.075 μg/i.c.v; Group IV: 0.15 μg/i.c.v; Group V: 0.3 μg/i.c.v; Group VI: 0.6 μg/i.c.v; Group VII: 1.2 μg/i.c.v; Group VIII: 2.4 μg/i.c.v). The various doses of hemopressin were injected intracerebroventricularly (i.c.v) 30 minutes after penicillin (2.5μl) injection. After hemopressin injection, ECoGs were recorded for three hours. Hp at doses of 0.075, 0.15, 0.3, 0.6, 1.2 and 2.4 μg/kg significantly increased the frequency of epileptiform ECoG activity compared to penicillin-injected group without changing the amplitude. The 0.6 µg hemopressin was the most effective dose to increase the epileptiform activity (p 0.05). The results of this study provided electrophysiological evidence for hemopressin to be modulating penicillin-induced epileptiform activity by acting as CB1 receptor antagonist. Further studies are required to elucidate the involved mechanism underlying this effect (Fig. 3, Ref. 40).

The effect of vitamin D3 and paricalcitol on penicillin-induced epileptiform activity in rats

AimEpilepsy is a disease characterized by seizures which impair human life considerably. Vitamin D is of different systemic effects on metabolism and its deficiency is known to have a high prevalence among epilepsy patients. Paricalcitol, a vitamin D receptor agonist, has relatively fewer side effects. This study aimed to investigate the anticonvulsant effect of vitamin D3 (cholecalciferol) and paricalcitol on penicillin-induced epileptiform activity. Method21 male Wistar rat weighing 180−240 g were used. After anesthetized by 1.25 g/kg urethane intraperitoneally (i.p.), rats were placed in the stereotaxic frame and tripolar electrodes were placed on the skull. The single microinjection of penicillin (2.5 μl, 500 IU, i.c.) into left sensorimotor cortex induced epileptiform activity. A single dose of 60.000 IU/kg (i.p.) vitamin D3 was administered 14 days before intracortical penicillin (500 IU) injection. Paricalcitol (10 μg/kg, i.p.) was administered 30 min before intracortical penicillin (500 IU) administration and recorded for the following 180 min. ResultsVitamin D3 pretreatment and paricalcitol diminished the frequency of epileptiform activity (p < 0.001) without changing the amplitude (p > 0.05) compared to the penicillin-injected group. Vitamin D3 pretreatment and paricalcitol led to an important delay in the onset of penicillin-induced epileptiform activity (p < 0.001 and p < 0.05, respectively). Vitamin D3 increased the latency of penicillin-induced epileptic activity compared to paricalcitol group (p < 0.001). ConclusionResults indicate that vitamin D3 and paricalcitol decreased the frequency and increased the latency of the penicillin-induced epileptic activity. Vitamin D3 was more effective than paricalcitol.

Effect of tadalafil and nitric oxide agonist sodium nitroprusside on penicillin-induced epileptiform activity

ABSTRACTObjective: Comorbidity of erectile dysfunction (ED) and epilepsy is not rare. Tadalafil is widely used in the treatment of ED and shows its effect by increasing nitric oxide (NO) level. Previous studies demonstrated that ED treatment drugs increased epileptiform activity in clinical studies and various experimental epilepsy models. Therefore, it is important to know whether an ED treatment drug has proconvulsion or anticonvulsant properties. This study was designed to demonstrate the effect of tadalafil and NO agonist sodium nitroprusside during penicillin-induced seizures in rats. The experimental penicillin epilepsy model is preferred in clinical studies of partial epilepsy.Methods: A single dose of penicillin (500 units) intracortical (i.c.) injection into the left sensorimotor cortex induced epileptiform activity. In the first set of experiments, tadalafil (20 mg/kg/intraperitoneal [i.p.]) and sodium nitroprusside (50 µg/intracerebroventricular [μg/i.c.v]) were administered 30 min after penicillin injection.In the second set of experiments, tadalafil (i.p) was administered 30 min after penicillin injection and sodium nitroprusside was administered simultaneously with the tadalafil injection.Results: Tadalafil, sodium nitroprusside and tadalafil+sodium nitroprusside groups decreased the frequency and amplitude of epileptiform activity in rats. Spike frequency of all groups decreased significantly 10 min after the administration and this decrease continued for 180 min. The mean amplitude of epileptiform activity significantly decreased 120 min after penicillin application in tadalafil or sodium nitroprusside applications. But this decrease was observed 110 min after tadalafil+sodium nitroprusside combined application.Conclusion: Data from the present study indicate that tadalafil has an anticonvulsion effect against penicillin-induced epileptiform activity in rats.

The effects of moderate running exercise and L-tyrosine on penicillin-induced epileptiform activity in rats

Regular exercise and amino acid supplementation, popular approaches toward the reduction of epileptic seizures, have been extensively researched. This study was conducted to evaluate the effects of treadmill exercise and L-tyrosine treatment on the frequency and amplitude of epileptiform activity in rats. A total of 32 male albino Wistar rats were randomly divided into four groups: control, exercise, L-tyrosine, and exercise + L-tyrosine. L‑tyrosine was supplemented by oral gavage (500 mg/kg/day, 2.5 mL solution). The treatments were performed 5 days a week for 10 weeks. The rats were anesthetized and then administered 500 IU penicillin into the left cerebral cortex using a microinjector and electrocorticogram (ECoG) activity was recorded for 3 hours using a Power Lab data acquisition system. The frequency and the amplitude of the ECoG recordings were analyzed offline. Compared to the control group, spike frequency decreased significantly in all other groups. There was no statistically significant difference between the groups in terms of spike amplitude and latency. In this study, the effects of regularly administered treadmill exercise and L-tyrosine use on epileptiform activity were examined and evaluated together for the first time. The results of this study showed that regular exercise and L-tyrosine use decreased epileptiform activity. Further research and clinical trials are needed to investigate the extent to which L-tyrosine and physical activity interfere with the epileptic state by investigating different doses of L-tyrosine and different severity/ time/type of exercise protocols.

The effect of duloxetine on penicillin-induced epileptiform activity in rats

ABSTRACTAim: Previous studies showed the existence of a relationship between epilepsy and depression. Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake (SNRI) used in the treatment of the major depressive disorder. The aim of the present study was to investigate the effect of duloxetine on penicillin-induced epileptiform activity in an experimental rat model of acute partial epilepsy.Method: In this study, 35 male rats weighing 200–240 g were used. Under urethane anesthesia, tripolar electrodes were placed for electrocorticography (ECoG) recording. Duloxetine, at 1, 5, 10 or 30 mg/kg rates, was administered intraperitoneally 30 minutes after intracortical penicillin (500 IU) injection.Results: Duloxetine administrations of 1, 5, 10 and 30 mg/kg increased the mean frequency of epileptiform activity 10 minutes after Duloxetine injection compared to the control group (p < 0.05) without changing amplitude in all groups (p > 0.05).Conclusion: The results showed proconvulsant effect of duloxetine in penicillin-induced epileptiform activity and indicated that it could pose complications risk for people with partial epilepsy.

Gül Yağının Sıçanlarda Penisilin İle Tetiklenen Epileptiform Aktivite Üzerine Etkileri: Elektrofizyolojik Bir Çalışma

Objective: Rose oil (from Rosa damascene) has several effects which are analgesic, antispasmodic, antioxidant and neuroprotective role. Its antiepileptic effect has not been yet studied enough. In the present study, it was aimed to investigate acute effects of rose oil on the epileptiform activity in penicillin-induced epilepsy model in rats.Methods: Forty-two male Wistar rats weighing 230 to 260 g were divided into six groups with seven rats in each group. Control (+Penicillin), RO alone, Diazepam, and different doses of Rose oil including 100, 500 and 1000 mg/kg. Rats were pretreated with different doses of RO 30 min prior to penicillin treatment. Electrocorticogram recordings were taken from each animal for 2 hours after penicillin treatment.Results: Only the dose of 100 mg/kg of rose oil reduced significantly epileptic spike-wave frequency of epileptiform activity. However, comparing in terms of latency and spike-wave amplitude of epileptiform activity, there were no significant difference between the groups.Conclusions: In conclusion, acute administration of rose oil reduces spike-wave frequency of penicillin-induced epileptiform activity in rats. Therefore, these findings indicate that rose oil has antiepileptic effects.

The effects of TGN-020 on penicillin induced epileptiform activity in rats

Objective: Aquaporin-4 (AQP-4) is a water channel protein which is the most abundant aquaporin isoform in the brain. Recent studies indicate the relationship between AQP-4 with epileptogenesis . Therefore, w e examined the potential effect of the AQP-4 inhibitor TGN-020 on penicillin-induced epileptiform activity in rats. Material and Method: Epileptiform activity was induced by intracortical (i.c.) administration of penicillin (200 IU, 1 μl). TGN-020, at doses of 25 µg, 50 µg, 100 µg and 200 µg, was administered by intracerebroventricular (i.c.v.) 30 minutes after penicillin injection. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. Twenty four hours later, animals are decapitated for the collection of blood samples and brain tissue. Results: The dose of 100 µg TGN-020 decreased the mean spike frequency of epileptiform activity in the 30 min after the injection without changing the amplitude (p < 0.05). Serum neuropeptide Y level was up-regulated by 25 µg TGN-020 in comparison with the other groups (p<0.001). Plasma levels of calcineurin in the 50 µ g dose of TGN-020 were lower than 25 µg and 200 µg doses of TGN-020 ( p<0.01) . E nzymatic ativity of glutathione peroxidase (GP x -1) in brain tissue was higher in the penicillin and 25 µg TGN-020 group compared with the sham group (p < 0.05). Conclusion: Given all these data, the anticonvulsant effect of TGN-020 which is aquaporin-4 water channel inhibitor in the brain has been studied extensively for the first time in an experimental model of epilepsy. Inhibition of AQP-4 might be useful in the treatment of epilepsy in future.

Interaction between urethane and cannabinoid CB1 receptor agonist and antagonist in penicillin-induced epileptiform activity.

Previous experimental studies have shown that various anesthetics alter the effects of cannabinoid agonists and antagonists on the cardiac response to different stimuli. Since no data have shown an interaction between urethane and cannabinoid signaling in epilepsy, we examined the suitability of urethane with regard to testing the effects of a cannabinoid CB1 receptor agonist and an antagonist on penicillin-induced epileptiform activity in rats. Permanent screw electrodes for electrocorticographic (ECoG) recordings, and a permanent cannula for administration of the substances to the brain ventricles, were placed into the cranium of rats. Epileptiform activity was induced by injection of penicillin through the cannula in conscious animal. The CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA; 7.5 μg) and the CB1 receptor antagonist [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide] (AM-251; 0.25 μg) were administered intracerebroventricularly 30 minutes after the penicillin application in urethane-anesthetized and conscious animals. Urethane completely eliminated spontaneous ictal events in ECoG recordings and reduced the frequency and total amount of epileptiform activity. It did not alter either the proconvulsant effects of AM-251 or the anticonvulsant effects of ACEA on penicillin-induced epileptiform activity. The electrophysiological evidence suggests that there is no possible interaction between urethane and cannabinoid CB1 receptors in this experimental model of epilepsy.

Proconvulsant Effect of Papaverine on Penicillin-Induced Epileptiform Activity in Rats.

Papaverine is a vasodilator agent that is an opium alkaloid. It exhibits its effects by inhibiting the phosphodiesterase enzyme. Papaverine administration is widely used to avoid symptomatic vasospasm after subarachnoid hemorrhage. We aimed, in this research, to study the effects of papaverine on the epileptic discharges stimulated by penicillin. Adult female Wistar rats (220±30 g) were included in this research (n=30). Rats were anesthetized with urethane (1.25 g/kg) and then the left cerebral cortex was reached by opening a burr hole with a drill. Penicillin G sodium salt (500 IU)(200 IU/1 μl) was injected into the left lateral ventricle to produce epileptiform activity. Thirty minutes before penicillin G sodium injection, papaverine was administered at doses of 5, 10, 20 or 40 mg/kg intraperitoneally. There was no significant difference in spike frequency between the control group and the groups given 5 mg/kg, 10 mg/ kg or 40 mg/kg papaverine, while 20 mg/kg papaverine significantly increased the spike frequency (p < 0.05). Papaverine augments the epileptiform activity produced by penicillin injection. It is important to remember that papaverine might induce convulsions in patients who have epilepsy. More research is required to understand the mechanisms of the proconvulsant influence of papaverine in epilepsy.

Gender Specificity of Genistein Treatment in Penicillin-Induced Epileptiform Activity in Rats

We investigated gender-dependent differences of genistein (isoflavone phytoestrogen) treatment in a penicillin-induced experimental epilepsy rat model. Twenty-eight adult Wistar Albino rats (14 females and 14 males) were devided into four groups, control and genistein-treatmed males and females. Genistein (100 μg/kg, i.p) or saline was given during 15 days before the electrocorticography (ECoG) recordings. The epileptiform activity was induced by penicillin G potassium salt (500 IU) injections into the left somatomotor cortex. Significant differences among the groups were found in the latency to onset of epileptiform activity. This value in the female control group was significantly longer than the latencies in the male control, male genistein, and female genistein groups (respectively, P = 0.002, 0.015, and 0.032). There were no significant differences regarding the spike/wave frequencies and amplitudes in epileptiform activity between female/male genistein and control groups within all observation intervals (P > 0.05). Thus, genistein exerts a proconvulsant effect in the penicillin-induced epilepsy model, and the effect demonstrates the clear gender specificity related to the specificity of hormonal backgrounds in males and females.

Effects of thymoquinone, the major constituent of Nigella sativa seeds, on penicillin-induced epileptiform activity in rats.

Objective:To investigate the effects of thymoquinone (TQ) in a penicillin-induced epilepsy model in rats.Methods:This experimental study included 56 adult male Wistar rats. Experiments were performed in the Research Laboratory of the Department of Physiology, Medical School, Duzce University, Duzce, Turkey, between October 2013 and December 2014. Animals were divided into the following 7 groups: sham, control, only thymoquinone, vehicle (Dimethylsulfoxide), and doses of 10, 50, and 100 mg/kg of TQ. After rats were anesthetized, the left part of the skull was removed. A pair of silver/silver chloride electrodes was placed on the somatomotor area, and electrocorticographic recording was started. After 5 minutes basal activity was recorded, and TQ was applied intraperitoneally. At the thirtieth minute after TQ, epileptiform activity was induced by intracortical penicillin. The first spike latency, spike frequency, and the amplitude of epileptiform activity were analyzed statistically.Results:The different doses of TQ significantly increased the latency time to onset of first spike wave, and decreased the frequency, and amplitude of epileptiform activity in the first 20 minutes compared with the control group.Conclusion:Thymoquinone shows potential as an antiepileptic drug resulting from its effects of prolonged latency time, and reduced spike wave frequency and amplitude of epileptiform activity.

Effects of intracortical microinjection of vitamin B12 on penicillin-induced epileptiform activity in rats

There are increasing studies indicating neuroprotective effects for vitamin B12. In the present study, the effect of intracortical microinjection of vitamin B12 was investigated on penicillin-induced epileptiform activity. We also examined the effects of intracortical microinjection of diazepam (a GABA-benzodiazepine receptor agonist) and flumazenil (a GABAbenzodiazepine receptor antagonist) to clarify the possible mechanism of vitamin B12. In urethane-anesthetized rats, epileptiform activity was induced by intracortical microinjection of penicillin (300 IU, 1.5 microL), and the number and amplitude of spike waves were analyzed using electroencephalographic (EEG) recordings. Intracortical microinjections of vitamin B12 at doses of 100 and 200 ng/site, diazepam at a dose of 200 ng/site and their ineffective doses (50 ng/site of vitamin B12 with 50 ng/site of diazepam) co-microinjection treatment significantly (P less than 0.05) reduced both the number and amplitude of spike waves. In addition, combined microinjection of effective doses of vitamin B12 (100 ng/site) and diazepam (200 ng/site) produced more antiepileptiform effect in comparison with their alone used doses. The antiepileptic effects induced by microinjection of vitamin B12 and diazepam at a same dose of 200 ng/site were prevented by the same site microinjection of 50 ng/site of flumazenil. The results showed antiepileptiform activities for vitamin B12 and diazepam AT the cerebral cortex level. A central GABA-benzodiazepine receptor complex-mediated mechanism might be involved in the antiepileptiform activity of vitamin B12.

Effect of levetiracetam on penicillin induced epileptic activity in rats.

The aim of this study was to investigate the effects of levetiracetam (LEV) on penicillin-induced epileptiform activity in rats. Penicillin was applied intracerebroventricularly (icv) at a dose of 500 IU to induce epileptiform activity. LEV was given intraperitoneally (ip) at doses of 20, 40, 80 mg/kg before penicillin injection. This agent reduced epileptiform activity by decreasing spike frequencies. The mean spike frequencies decreased significantly in all the LEV treated groups. There was no significant change in the spike amplitudes of the LEV groups compared with the control group. 40 mg/kg of LEV was determined as the most effective dose on reducing epileptiform activity. The results of this study suggest that LEV is an effective antiepileptic agent in penicillin-induced epilepsy.

The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats

The majority of experimental and clinical studies show that ghrelin and cannabinoids are potent inhibitors of epileptic activity in various models of epilepsy. A number of studies have attempted to understand the connection between ghrelin and cannabinoid signalling in the regulation of food intake. Since no data show a functional interaction between ghrelin and cannabinoids in epilepsy, we examined the relationship between these systems via penicillin-induced epileptiform activity in rats. Doses of the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) (2.5 and 7.5 µg), the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide (AM-251) (0.25 and 0.5 µg) and ghrelin (0.5 and 1 µg) were administered intracerebroventricularly (i.c.v.) 30 minutes after the intracortical (i.c.) application of penicillin. In the interaction groups, the animals received either an effective dose of ACEA (7.5 µg, i.c.v.) or a non-effective dose of ACEA (2.5 µg, i.c.v.) or effective doses of AM-251 (0.25, 0.5 µg, i.c.v.) 10 minutes after ghrelin application. A 1 µg dose of ghrelin suppressed penicillin-induced epileptiform activity. The administration of a 0.25 µg dose of AM-251 increased the frequency of penicillin-induced epileptiform activity by producing status epilepticus-like activity. A 7.5 µg dose of ACEA decreased the frequency of epileptiform activity, whereas a non-effective dose of ACEA (2.5 µg) did not change it. Effective doses of AM-251 (0.25, 0.5 µg) reversed the ghrelin's anticonvulsant activity. The application of non-effective doses of ACEA (2.5 µg) together with ghrelin (0.5 µg) within 10 minutes caused anticonvulsant activity, which was reversed by the administration of AM-251 (0.25 µg). The electrophysiological evidence from this study suggests a possible interaction between ghrelin and cannabinoid CB1 receptors in the experimental model of epilepsy.

Efficacy of dexamethasone on penicillin-induced epileptiform activity in rats: An electrophysiological study

Corticosteroids are extensively used in treatment of many diseases. In neurosurgery practice, dexamethasone (DEX) is commonly used particularly in cerebral edema secondary to brain tumors, head trauma, and central nervous system infections. There are some uncertainties surrounding the secure use of DEX in patients with epilepsy or seizures induced by diseases of the central nervous system such as head trauma and brain tumors. Despite its extensive use, the effect of DEX on epileptiform activity is unclear. In this study the effect of DEX on epileptiform activity was investigated in rats. The effects of 1, 3, and 10mg/kg DEX on epileptiform activity was compared with effects of antiepileptic drugs commonly employed in treatment of epilepsy, namely phenytoin (PHT) 50mg/kg and levetiracetam (LEV) 50mg/kg that were administered intraperitoneally for 1 week. All groups were administered intracortical penicillin (500IU) to induce epileptiform activity. DEX at the doses of 3mg/kg and 10mg/kg significantly reduced spike frequencies compared to the initial values. In conclusion, we think that DEX can effectively decrease the epileptiform activity.