Epileptiform Activity In Rats Research Articles

The effect of acute and chronic harmaline administration on penicillin induced epileptiform activity in rats

Aim: The electrophysiological impact of short-term and long-term harmaline treatment on the penicillin G-induced epileptic model in rats was examined in this study. Methods: Eighty-four adult male Wistar rats were randomly assigned to two groups: one received a single dose of harmaline, and the other received repeated doses of harmaline. Each group was further divided into six subgroups based on the dose of harmaline (0, 10, 50, or 100 mg/kg) or penicillin (control or sham). The electrophysiological data were collected using electrocorticography and analyzed using PowerLab Chart v.8 software. The statistical analysis included the latency, frequency, and amplitude of the spike-wave discharges. The serum levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were measured using the ELISA method to assess the antioxidant effects of harmaline. Results: The results showed that both acute and chronic harmaline treatment increased the seizure threshold in a dose-dependent manner (p

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 minocycline on total oxidant-antioxidant levels and penicillin induced epileptiform activity in rats

Effect of minocycline on total oxidant-antioxidant levels and penicillin induced epileptiform activity in rats

Investigation of the Effect of Propolis on Penicillin Induced Epileptiform Activity in Rats

Aim: The aim of this study was to investigate the effects of propolis (PP), which has antioxidant and neuroprotective effects, on penicillin-induced epileptiform activity in rats. Material and Methods: Forty-two adult male Wistar rats were divided into 6 groups as control (CONT), penicillin (PEN), diazepam (DZM), only propolis (OPP), 50 mg/kg propolis (PP50), and 100 mg/kg propolis (PP100). ECoG recording was taken from rats. At the end of the experiment, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were determined from serum samples. Moreover, the latency of the first epileptiform activity, spike-wave frequency (SWF), and spike-wave amplitude (SWA) of the epileptiform activity were analyzed. Results: The latency of the DZM and PP100 groups was found to be longer than the CONT groups. The time-dependent SWF and total SWF of the PP50 and PP100 groups were lower than the CONT group. No significant difference was found between the groups in terms of SWA. SOD, CAT, and GPx levels were found to be higher, but the MDA level was lower in PP50 and PP100. Conclusion: As a result, propolis may be a potential antiepileptic drug candidate in the future with its antioxidant activity as well as prolonging latency and reducing SWF in epilepsy models.

4-AP challenge reveals that early intervention with brivaracetam prevents posttraumatic epileptogenesis in rats

PurposeThere are currently no clinical treatments to prevent posttraumatic epilepsy (PTE). Recently, our group has shown that administration of levetiracetam (LEV) or brivaracetam (BRV) shortly after cortical neurotrauma prevents the development of epileptiform activity in rats, as measured ex vivo in neocortical slices. Due to the low incidence of spontaneous seizures in rodent-based models of traumatic brain injury (TBI), chemoconvulsants have been used to test injured animals for seizure susceptibility. We used a low dose of the voltage-gated potassium channel blocker 4-aminopyridine (4-AP) to evaluate posttraumatic epileptogenesis after controlled cortical impact (CCI) injury. We then used this assessment to further investigate the efficacy of BRV as an antiepileptogenic treatment. MethodsSprague-Dawley rats aged P24–35 were subjected to severe CCI injury. Following trauma, one group received BRV-21 mg/kg (IP) at 0–2 min after injury and the other BRV-100 mg/kg (IP) at 30 min after injury. Four to eight weeks after injury, animals were given a single, low dose of 4-AP (3.0–3.5 mg/kg, IP) and then monitored up to 90 min for stage 4/5 seizures. ResultsThe chemoconvulsant challenge revealed that within four to eight weeks, CCI injury led to a two-fold increase in percentage of rats with 4-AP induced stage 4–5 seizures relative to sham-injured controls. Administration of a single dose of BRV within 30 min after trauma significantly reduced injury-induced seizure susceptibility, bringing the proportion of CCI-rats that exhibited evoked seizures down to control levels. ConclusionsThis study is the first to use a low dose of 4-AP as a chemoconvulsant challenge to test epileptogenicity within the first two months after CCI injury in rats. Our findings show that a single dose of BRV administered within 30 min after TBI prevents injury-induced increases in seizure susceptibility. This supports our hypothesis that early intervention with BRV may prevent PTE.

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.

In vivo electrophysiological study of vitamin D3 protective effects on PTZ-induced seizures in rats.

The purpose of the current study was to investigate the protective effects of acute and chronic administration of different doses of vitamin D3 on pentylenetetrazol (PTZ)-induced epileptiform activities in rats. Sixty Wistar rats in chronic and acute groups were used in this study. In the chronic groups, animals received vitamin D3 at 50, 100, and 150 μg/kg; vitamin D3 (50 μg/kg, i.p.) + diazepam (0.1 mg/kg, i.p.), and almond oil (i.p.) daily for two weeks whereas, in the acute groups the animal received a single dose of chemicals just 30 min before PTZ administration. The electrophysiological recording was performed by implanting a unilateral bipolar electrode in the pyramidal cell layer of the CA1 region of the hippocampus. Epileptic activities were induced by intraperitoneal injection of PTZ (80 mg/kg, i.p.). The spike count and amplitude were analyzed using the eTrace software. Chronic administration of all doses of vitamin D3 and its combination with diazepam significantly reduced both spike counts and amplitudes following PTZ administration. While the acute doses were ineffective. The results of the study indicated that chronic but not acute administration of vitamin D3 has a protective effect on PTZ-induced epileptiform activity in rats.

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.

The Effects of Acute and Chronic Metformin Treatment on Penicillin Induced Epileptiform Activity in Rats

The Effects of Acute and Chronic Metformin Treatment on Penicillin Induced Epileptiform Activity in Rats

An involvement of COX and 5-LOX pathways in the penicillin- and pentylenetetrazole (PTZ)-induced epilepsy models.

This study aimed to examine the relationship between epilepsy and COX/5-LOX inflammation pathways in the penicillin and pentylenetetrazole (PTZ)-induced epilepsy models. For this purpose, 42 albino male Wistar rats were used in this study. In the penicillin and PTZ-induced epilepsy models, epileptiform activity was induced by injection of penicillin (500 IU, i.c.) and PTZ (35 mg/kg, i.p., three times a week), respectively. Licofelone (20 mg/kg, i.p.), a dual inhibitor of COX/5-LOX, and esculetin (20 mg/kg, i.p.), a 5-LOX inhibitor, were given. In the penicillin-induced epilepsy model, ECoG activity was recorded for 180 min. In the PTZ-induced epilepsy model, both ECoG activity was recorded, and behavioral parameters were performed. In the penicillin groups, both licofelone and esculetin decreased the mean spike frequency and amplitude during the experiments. In the PTZ groups, licofelone (20 mg/kg, i.p.) was more effective than esculetin (20 mg/kg, i.p.). Licofelone showed its protective effects both in ECoG activity and in behavioral parameters. Esculetin was less effective when compared to licofelone. The electrophysiological and behavioral data from the present study indicated that inflammation pathways might have a crucial role in controlling epileptiform activity in rats. Licofelone might be a valuable candidate in advanced studies.

Vortioxetine suppresses epileptiform activity and cognition deficits in a chronic PTZ-induced kindling rat model.

This study aimed to examine the effects of vortioxetine, a novel antidepressant, on epileptiform activity in pentylenetetrazole (PTZ)-induced kindling model in rats. For this purpose, 20 male Wistar Albino rats were used, and epileptiform activity was induced by injection of PTZ (35mg/kg, i.p., three times a week). In the vortioxetine groups, vortioxetine (5mg/kg and 10mg/kg) was administered before the kindling process. During the kindling process, the Fisher and Kittner seizure scales were used to score seizure severity. After kindling, novel object recognition (NOR) tests were performed to evaluate the cognitive performance of rats. Electrodes were implanted into the fully kindled animals for ECoG recordings. In the PTZ group, the number of total spikes was 1367±136 spikes/20minutes. First myoclonic jerks decreased while seizure severity and total spike count increased in the PTZ group. On the other hand, the total spike number and seizure severity significantly decreased and first myoclonic jerks increased in the vortioxetine groups compared to the PTZ group. Based on the NOR test, vortioxetine administration markedly raised the discrimination index compared to the PTZ group. Electrophysiological and behavioural data from the present study suggest that vortioxetine, a novel drug, plays a critical role in controlling PTZ-induced epileptiform activity in rats. Vortioxetine may therefore be a valuable candidate to prevent seizure activity and treat cognitive deficits associated with 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.

Alpha adrenergic receptors have role in the inhibitory effect of electrical low frequency stimulation on epileptiform activity in rats

Aim: Low frequency stimulation (LFS) inhibits neuronal hyperexcitability following epileptic activity. However, knowledge about LFS’ inhibitory mechanisms is lacking. Here, α1 and α2 adrenergic receptors’ roles in mediating LFS inhibitory action on high-K+ induced epileptiform activity (EA) was examined in rat hippocampal slices. Materials and methods: LFS (1 Hz, 900 pulses) was applied to the Schaffer collaterals. Whole-cell, patch clamp recording was used to measure changes in CA1 pyramidal neurons’ excitability. By applying high-K+ on hippocampal slices, EA was induced, and neuronal excitability increased. Results: When administered at the beginning of EA, LFS reduced neuronal excitability. In the presence of prazosin (10 µM, an α1 adrenergic receptor antagonist) and yohimbine (5 µM, an α2 adrenergic receptor antagonist), LFS’ typically has a restorative impact on EA-induced membrane potential hyperpolarization and spike firing frequency, but this effect was reduced after high-K+ washout; These antagonists did not have a significant effect on LFS’ inhibitory action on spike firing during EA. Conclusion: These findings suggest that LFS’ anticonvulsant effect, on neuronal hyperexcitability following high-K+ EA, may be mediated partly through α adrenergic receptors in hippocampal slices.

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.