Penicillin-induced Epileptiform Activity Research Articles

Role of cannabinoid CB1 receptors in the proconvulsant effect of Apelin-13 on penicillin-induced epileptiform activity

Role of cannabinoid CB1 receptors in the proconvulsant effect of Apelin-13 on penicillin-induced epileptiform activity

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

Limited Exposure to Social Isolation does not Affect the Spike Frequency and Amplitude of Penicillin-induced Epileptiform Activity in Adolescent Rats

Limited Exposure to Social Isolation does not Affect the Spike Frequency and Amplitude of Penicillin-induced Epileptiform Activity in Adolescent Rats

Penı̇sı̇lı̇n ile Oluşturulan Deneysel Epilepsi Modelinde Seftrı̇aksonun Etkı̇sı̇: Elektrofı̇zyolojı̇k Bı̇r Çalışma

Introduction: Epilepsy is a set of chronic neurological disorders characterized by seizures associated with abnormal and uncontrolled neuronal activity of the brain. Glutamate is the main excitatory neurotransmitter in the central nervous system. Excitatory amino acid transporter-2 (EAAT2), one of the major glutamate transporters, is responsible for total glutamate intake. Ceftriaxone is a β-lactam antibiotic that increases EAAT-2 expression and functional activity. This study aims to investigate the effects of ceftriaxone on penicillin-induced epileptiform activity by using electrocorticography (ECoG) in anesthetized rats.
 Materials and Methods: In this study, 35 Wistar male rats were used. The rats were divided into five groups of 7. In group 1, 2.5 μL 500 IU of penicillin intracranially (i.c.) and 1 ml saline solution and intraperitoneally (i.p.) were given, respectively. In group 2, 200 mg/kg, i.p. of ceftriaxone was administered 30 minutes after penicillin. In group 3, 400 mg/kg of ceftriaxone was administered i.p. 30 minutes after penicillin. 500 mg/kg of sodium valproate was administered i.p. following 30 minutes of penicillin in group 4. In group 5, 400 mg/kg, i.p. of ceftriaxone and 500 mg/kg, i.p. of sodium valproate were administered 30 minutes after penicillin. The rats were placed in a stereotaxic device after the procedure, and electrocorticogram recordings were captured for 180 minutes.
 Results: The acute treatment of ceftriaxone reduced spike-wave frequency and spike-wave amplitude of penicillin-induced epileptiform activity in the rats. 
 Conclusion: These findings suggest that acute ceftriaxone had an anticonvulsant effect on penicillin-induced focal onset epileptic activity. Ceftriaxone may has an anti-epileptogenic potential.

Investigation of the Antiepileptic Effect of (R)-(-) and (S)-(+) Carvone in Penicillin-Induced Epileptiform Activity Model

Aim: Epilepsy affects approximately 70 million people worldwide. While many drugs can prevent seizures, they have a limited impact on preventing or curing the disease. In this perspective, natural compounds, especially monoterpenes derived from medicinal plants, have been investigated in epilepsy models, such as carvone (CAR). The principal constituent of peppermint oil, (R)-(-)-carvone (R-CAR), and the primary component in cumin and dill seed oils, (S)-(+)-carvone (S-CAR), find diverse applications in cosmetics, food, and pharmaceutical formulations. This study aims to investigate the antiepileptic effects of the natural compounds S-CAR and R-CAR in penicillin (PEN)-induced experimental epilepsy model in rats.
 Material and Method: In the research, 91 male Wistar rats were used. The rats were grouped into 3 main groups as common groups, pre-penicillin groups and post-penicillin groups. The main groups were divided into a total of 13 subgroups. Electrocardiogram recording was taken from rats. At the end of the experiment, the latency of the first epileptiform activity (EA), spike-wave frequency (SWF), and spike-wave amplitude (SWA) of the EA were analyzed. 
 Results: S-CAR and R-CAR administered before penicillin prolonged the latency to the onset of the first EA. S-CAR and R-CAR administered before penicillin decreased SWF. 100 mg/kg doses of S-CAR and R-CAR injected 30 minutes after penicillin administration decreased SWF. While 200 mg/kg dose of R-CAR administered before penicillin decreased SWA in a time-dependent manner, 100 mg/kg dose of S-CAR administered after penicillin decreased SWA.
 Conclusion: These findings indicate that carvone could exhibit both protective and therapeutic effects in the management of epilepsy.

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.

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.

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

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.

INVESTIGATION OF THE THERAPEUTIC AND PROTECTIVE EFFECTS OF ATP SENSITIVE POTASSIUM CHANNEL (KATP) AGONISTS AND ANTAGONISTS ON PENICILLIN INDUCED EXPERIMENTAL EPILEPSY MODELS IN RATS

Epilepsy is a disease occurring because of extreme activation of nervous system. Increased glutamate and Ca++ in brain is another reason of epilepsy. In this study, we investigated the effects of ATP sensitive potassium channel (KATP) agonists and antagonists on penicillin induced epileptiform activity in male wistar albino rats. Rats were divided three experimental main groups; (1) Control, (2) Before seizures (BS) groups, (3) During seizure (DS) groups. DS and BS groups are divided into four subgroups; (a)5HD, (b)HMR1098, (c)Bepridil (d)P 1075. Bepridil and p1075, reduce the number of spike-waves, while the effect of Bepridil appears to have a similar effect when administered both during and before the seizure. HMR1098 and 5-HD both increased the seizures both when administered before or during the seizure, different from the other studies. When K ATP channel agonists are administered before and during the seizure, they reduce the seizures, while antagonists increase the seizure.

The effect of penicillin-induced epileptiform activity on proinflammatory cytokines levels in the rat brain

Emerging evidence indicates a pathogenic role of protracted neuroinflammation in the various neurodegenerative diseases, including epilepsy. Neuroinflammation may contribute to neuronal hyperexcitability underlying seizure formation. The current research aims to examine the changes in the levels of proinflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the penicillin epilepsy model. In the present study, 12 male Wistar albino rats were randomly divided into two groups as sham and penicillin epilepsy model. Seizures were induced with the intracortical (i.c.) single microinjection 500 IU of penicillin-G into neocortex. Rats were decapitated after observing the cortical epileptic activity and brains were removed by craniotomy. Proinflammatory cytokines (TNF-α and IL-1β) were measured by using ELISA methods in the cortical and hippocampal brain regions. Penicillin significantly up-regulated the expression of IL‑1β and TNF-α in the rat cortex, but did not affect the hippocampal cytokines levels. This study is indicative of the neuroinflammatory potential of cortical penicillin administration.

Anticonvulsive effects of edaravone on penicillin-induced focal onset seizure model in the conscious rats.

Edaravone is a potent antioxidant and anti-inflammatory agent that is used in the clinic. The aim of the present study was to evaluate the chronic treatment effect of edaravone on penicillin-induced epileptiform activity. Twenty-eight Wistar rats were randomly divided into a total of four groups as penicillin control and edaravone pretreatment groups (1, 10, and 30mg/kg). Firstly, permanent electrodes for electrocorticography (ECoG) recording and canula for penicillin injection were placed as stereotactic under anesthesia. At the end of the recovery period, edaravone pretreatment groups received different doses of edaravone by intraperitoneal injection for 14 days and before 30-min penicillin microinjection. Epileptiform activity was induced by injecting 500 IU penicillin through the intracortical cannula. The effects of edaravone pretreatment on epileptiform activity were evaluated by using both electrophysiological and behavioral parameters. Edaravone pretreatment suppressed epileptiform activity by reducing the mean spike frequency and the behavior scores in ECoG recording. The results of the present study indicated that the use of chronic edaravone had an anticonvulsant effect on penicillin-induced focal onset epileptic activity. Edaravone had an anticonvulsant effect even at low doses.

Physical exercise and 5-hydroxytryptophan, a precursor for serotonin synthesis, reduce penicillin-induced epileptiform activity

AimPrevious studies have shown that 5- hydroxytryptophan (5-HTP) and exercise play an important role in the synthesis of serotonin independently. The effects of the treadmill exercise and 5‐ hydroxytryptophan (5-HTP) on seizure mechanisms created by epileptiform activity with penicillin model were investigated in rats. MethodA total of 28 male albino Wistar rats were randomly divided into four groups: exercise (Ex), Control (Cnt), 5‐hydroxytryptophan (5htp) and 5-hydroxytryptophan + exercise (5htpEx) groups. Treadmill exercise and gavage (25 mg/kg/day) were administered five days a week for ten weeks. Electrocorticogram data were recorded for 3 h at the end of the protocol using the Power-Lab data acquisition system. Spike frequency, amplitude, and latency time were analyzed offline. The significant differences among the groups were evaluated by one-way analysis of variance (ANOVA). ResultsSpike frequency was observed at the highest level from the 20th minute in the Cnt group, and this continued until the end of the recording. The 5-HTP alone group did not affect epileptiform activity. At the 80th minute of penicillin injection, the epileptiform activity in the 5htpEx group decreased significantly compared with the Cnt, and this significance continued until the 110th minute. There was no statistical difference in the amplitude values of the groups. The 5htpEx group was significantly higher than both the Cnt and Ex group in the seizure latency times. ConclusionsIt was determined that exercise reduced the spike number and delayed seizure significantly by potentiating the effect of 5-HTP. Given that 5-HTP used in combination with exercise can perform useful actions such as reducing seizure sensitivity and consequently improving the quality of life for individuals with epilepsy, it may be a potential candidate for the treatment of epilepsy in nonpharmacological methods.

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.

Trazodone increases seizures in a genetic WAG/Rij rat model of absence epilepsy while decreasing them in penicillin-evoked focal seizure model

AimPsychiatric disorders, especially depression and anxiety, are among the most disabling comorbidities in patients with epilepsy, and they are difficult to treat because many antidepressants cause proconvulsive effects. Thus, it is important to identify the seizure risks associated with antidepressants. Trazodone is one of the most frequently prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs for the treatment of depression and anxiety. The aim of the present study was to evaluate the effects of trazodone on epileptiform activity in a penicillin-evoked focal seizure model in Wistar rats and in a genetic absence epilepsy model in Wistar Albino Glaxo/Rijswijk strain (WAG/Rij) rats. MethodsTrazodone at 5-, 10-, and 30-mg/kg doses was injected intraperitoneally in Wistar rats 30 min after penicillin injection, and spike frequency and amplitude of penicillin-induced epileptiform activity were evaluated. In a separate experimental model, the same trazodone doses were injected in WAG/Rij rats to elucidate their effects on number, duration, and amplitude of spike-and-wave discharges (SWDs) and on depression–anxiety like behavior. In both experimental groups, after trazodone injections recordings were made for 3 h. Depression–anxiety like behaviors in WAG/Rij rats were examined using forced swim test and open-field test. ResultsTrazodone at 10- and 30-mg/kg doses significantly reduced the frequency of penicillin-induced epileptiform activity without changing the amplitude. Trazodone at a 5-mg/kg dose had no effect on either frequency or amplitude of epileptiform activity. Trazodone at all doses significantly increased number and duration of SWDs without changing the amplitude. In addition, all doses of trazodone decreased the number of squares crossed and duration of grooming in open-field test, and reduced swimming time activity and increased immobility time in forced swim test. ConclusionOur results suggest that depending on the dose used, trazodone had an anticonvulsant effect or no effect on penicillin-evoked focal seizure model, but all trazodone doses resulted in proconvulsant and depression–anxiety like behavior in WAG/Rij rats, which represent a genetic absence model of epilepsy.