Penicillin-induced Epileptiform Research Articles

The role of nitric oxide in the anticonvulsant effects of pyridoxine on penicillin-induced epileptiform activity in rats

The present study was conducted to identify the role of nitric oxide (NO) in the anticonvulsant effects of pyridoxine hydrochloride on penicillin-induced epileptiform activity in rats. A single microinjection of penicillin (500 units) into the left sensorimotor cortex induced epileptiform activity within 2-4 min, progressing to full seizure activity lasting about 3-5h. Thirty minutes after penicillin injection, 20, 40, 80, and 160 mg/kg of pyridoxine hydrochloride was administered intraperitoneally (i.p.). Pyridoxine significantly reduced the frequency of penicillin-induced epileptiform activity. A low dose of pyridoxine (40 mg/kg) was the most effective in reducing both the frequency and amplitude of epileptiform activity. The effect of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective N(G)-nitro-L-arginine methyl ester (L-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO substrate, L-arginine on anticonvulsive effects of pyridoxine was investigated. The administration of L-arginine (500 mg/kg, i.p.) and 7-NI (25 and 50 mg/kg, i.p.) significantly decreased the frequency of epileptiform electrocorticographical (ECoG) activity while administration of L-NAME (60 mg/kg, i.p.) and the inactive form of arginine (D-arginine) did not influence it. The administration of L-NAME (60 mg/kg, i.p.) 15 min before pyridoxine (40 mg/kg i.p.) application reversed the anticonvulsant effects of pyridoxine whereas 7-NI (25 and 50 mg/kg, i.p.) did not influence it. The same dose of its inactive enantiomer N(G)-nitro-D-arginine methyl ester (d-NAME) failed to reverse the anticonvulsant effects of pyridoxine. The administration of L-arginine (500 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in the pyridoxine administered group. L-arginine did not reverse the anticonvulsant effect of 7-NI in the penicillin and pyridoxine administered groups. The results of present study indicate that the inhibitory effect on the anticonvulsant activity of pyridoxine against penicillin-induced epileptiform activity was produced by L-NAME, not by 7-NI, and is probably not related to the decrease of NOS activity in the brain.

The Effects of Ascorbic Acid on Penicillin‐induced Epileptiform Activity in Rats

Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as alpha-tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin-induced epileptiform activity. A single microinjection of penicillin (2.5 microl, 500 units, intracortically) into the left sensorimotor cortex induced epileptiform activity within 2-5 min, progressing to full seizure activity lasting approximately 3-5 h. In the first set of experiments, 30 min after penicillin injection, six different doses of ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered intraperitoneally (IP). The other group of animals received the effective dose of ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was stopped 24 h before penicillin treatment. Another group of rats received the effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin treatment. In the second set of experiments, the lipid peroxidation (MDA) and reduced glutathione (GSH) levels of brain were measured in the control, control + ascorbic acid, penicillin, and penicillin + ascorbic acid groups. Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin injection), decreased both the frequency and amplitude of penicillin-induced epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400 mg/kg, 30 min after penicillin injection), decreased the frequency of epileptiform activity without changing the amplitude. Ascorbic acid, at the lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin injection), did not change either the frequency or amplitude of epileptiform activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose in changing the frequency and amplitude of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin treatment caused a significant delay in the onset of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did not change the latency of epileptiform activity. The most effective dose of ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the increase in lipid peroxidation level (MDA) occurring after penicillin-induced epileptiform activity. These data indicate that ascorbic acid has neuroprotective activity against penicillin-induced epileptiform electrocorticogram activity.

Anticonvulsive effects of quinine on penicillin-induced epileptiform activity: An in vivo study

Epilepsy is an important problem in neurological disorders. The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. Recent studies claimed that gap junctions have a critical role in epileptic neuronal events. The aim of present study is to investigate the effects of connexin36 (Cx36) channel blocker quinine on penicillin-induced experimental epilepsy. For this purpose, 4 months old male Wistar rats were used in the present study. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. At the end of the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When the epileptiform activity, monitored from a digital recording system, reached maximal frequency and amplitude, quinine (200, 400 or 1000 nmol) was administered similar to penicillin. Effects of quinine on epileptiform activity were assessed by both electrophysiological and behavioral analysis. Quinine suppressed epileptiform activity by decreasing the amplitude and frequency of epileptiform spikes and by attenuating the epileptiform behavior. The outcomes of this study suggest that the blockade of Cx36 channels may contribute to the amelioration of epileptic activity.

The influence of ethanol intake and its withdrawal on the anticonvulsant effect of α-tocopherol in the penicillin-induced epileptiform activity in rats

Previous studies proposed the existence of a relationship between epilepsy and ethanol. Ethanol may have either proconvulsive or anticonvulsive effects on epileptic activity in different experimental epilepsy models. The influence of high dose ethanol intake and its withdrawal on the anticonvulsant effect of α-tocopherol was examined after intracortical injection of penicillin (500 units) to induce epileptiform activity. Thirty minutes after penicillin injection, the most effective dose of α-tocopherol (500 mg/kg) was administrated intramuscularly (i.m.). Ethanol-treated rats received a daily dose of 9.0 g/kg of 30% ethanol solution via an oesophageal probe for 15 days. All rats in the withdrawal group were anesthetized for induction of penicillin-induced epileptiform activity 28 h after the last ethanol administration. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. Ethanol, in a dose of 9 g/kg, significantly decreased the mean frequency of penicillin-induced epileptiform ECoG activity without changing the amplitude. The mean frequency of ECoG activity was decreased in the 60 and 70 min period from penicillin injection in the ethanol-treated + α-tocopherol and ethanol withdrawal + α-tocopherol groups compared with the penicillin-injected (500 units, i.c.) group, respectively. α-Tocopherol was more effective in decreasing the mean frequency of epileptiform activity in the ethanol + α-tocopherol group than in other α-tocopherol administrated groups. Ethanol withdrawal caused an increase in frequency of epileptiform activity in the withdrawal + α-tocopherol group compared with other α-tocopherol administrated groups. α-Tocopherol did not affect the amplitude of epileptiform activity in any group. Possible mechanisms of ethanol influence on the neuroprotective actions of α-tocopherol are still a crucial issue associated with epilepsy.

Anticonvulsant effects of focal and intracerebroventricular adenosine on penicillin-induced epileptiform activity in rats

Adenosine has potent anticonvulsant effects on various models of experimental epilepsy. In the present study, we examined the effects of focal and intracerebroventricular (i.c.v.) adenosine on penicillin-induced epileptiform activity in Wistar rats. The effects of theophylline, a non-selective adenosine receptor antagonist, were also researched. The recordings of electrocorticogram (ECoG) were carried out by using a data acquisition system, under urethane anesthesia. Adenosine was given in doses of 1, 10 and 100 μg/rat via focal and i.c.v. 30 min after penicillin administration. Theophylline was injected in doses of 1, 10 and 100 μg/rat by i.c.v. too. Adenosine administration significantly decreased the spike frequency while theophylline increased. Focal adenosine is more effective than i.c.v. adenosine. 100 μg adenosine is an effective dose that causes a decrease in epileptiform activity during experiments. We also demonstrated that 100 μg theophylline significantly increased epileptiform activity. Our findings suggest that focal adenosine is more effective than i.c.v. adenosine on epileptiform activity.

The involvement of nitric oxide in the anticonvulsant effects of α-tocopherol on penicillin-induced epileptiform activity in rats

A variety of animal seizure models exist which help to document the effects of alpha-tocopherol (Vitamin E) and specify its action. In the present study, we provide further evidence for the functional involvement of NO in the anticonvulsant effects of alpha-tocopherol on penicillin-induced epileptiform electrocorticographical (ECoG) activity in rats. The epileptiform ECoG activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, the most effective dose of alpha-tocopherol (500 mg/kg) was administrated intramuscularly (i.m.). Alpha-tocopherol decreased the frequency of penicillin-induced epileptiform ECoG activity without changing the amplitude. The effect of systemic administration of nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and NO substrates, L-arginine and sodium nitro prusside (SNP) on anticonvulsive effects of alpha-tocopherol was investigated. The administration of L-NAME (60 mg/kg, i.p.) did not influence the frequency of epileptiform ECoG activity while administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) significantly decreased in the penicillin-treated group. The administration of L-NAME (60 mg/kg, i.p.) 10 min after alpha-tocopherol (500 mg/kg, i.m.) application reversed the anticonvulsant effects of alpha-tocopherol. The administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in alpha-tocopherol supplemented group. L-arginine and SNP did not provide an additional anticonvulsant effect in alpha-tocopherol supplemented group. These results support the involvement of the nitric oxide pathway in the anticonvulsant effect of alpha-tocopherol on the penicillin-induced epileptiform ECoG activity.

Anticonvulsive effects of carbenoxolone on penicillin-induced epileptiform activity: An in vivo study

Epilepsy is an important problem in neurological disorders. Recent studies claimed that gap junctions have a critical role in epileptic neuronal events. The aim of present study is to investigate the effects of gap junction blocker carbenoxolone on penicillin-induced experimental epilepsy. For this purpose, 4-month-old male Wistar rats were used in the present study. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. At the end of the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. Epileptiform activity monitored from a digital recording system, when it reached its maximum intensity, carbenoxolone (100, 200, 500 nmol) was applied in the same way with penicillin. Effects of carbenoxolone on epileptiform activity were assessed by both electrophysiological and behavioral analysis. Carbenoxolone suppressed epileptiform activity by decreasing the amplitude and frequency of epileptiform spikes and by attenuating the epileptiform behavior. The results of this study suggest that the blockade of electrical synapses may contribute to the prevention and amelioration of epileptic activity.

The effects of ethanol intake and withdrawal on penicillin-induced epileptiform activity in rats

Previous experiments have shown that ethanol may have either pro-convulsive or anti-convulsive effects on epileptic activity in different experimental epilepsy models. In this study, the effect of low dose ethanol and its withdrawal on penicillin-induced epileptiform activity in rat was investigated. Eight groups of adult, male Wistar rats were studied: (1) control, (2) penicillin pretreated (500 units), (3) α-tocopherol (500 mg/kg, i.m.), (4) penicillin pretreated + α-tocopherol, (5) ethanol-treated (3 g/kg, per day, for 15 days, intragastrically) + penicillin, (6) ethanol-treated + penicillin + α-tocopherol, (7) ethanol withdrawal + penicillin, (8) ethanol withdrawal + penicillin + α-tocopherol. Each animal group was composed of seven rats. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. The epileptiform activity was induced by microinjection of penicillin into the left sensorimotor cortex. Administration of ethanol (3 g/kg, per day, for 15 days, intragastrically) did not change either frequency or amplitude of penicillin-induced epileptiform activity. The frequency and amplitude of epileptiform activity were evaluated 40 h after the last ethanol administration in withdrawal groups. There was no significant change in the mean frequency and amplitude of epileptiform activity compared with penicillin pretreated and ethanol-treated groups. The effective dose of α-tocopherol (500 mg/kg, i.m.) significantly decreased the mean frequency of epileptiform activity in the 60, 70, and 120 min after α-tocopherol injection in penicillin pretreated, ethanol-treated, ethanol withdrawal groups, respectively. However, α-tocopherol did not affect the amplitude of epileptiform activity in all groups. In conclusion, the present results indicate that low dose of ethanol does not have either anticonvulsive or proconvulsive effect on penicillin-induced epileptiform activity. α-Tocopherol has anti-convulsive effect on penicillin-induced epileptiform activity in effective dose.

Anticonvulsive effects of nimodipine on penicillin-induced epileptiform activity

The common features of all types of epilepsy are synchronized and uncontrolled discharges of nerve cell assemblies. It is believed that calcium ions play an important role in the generation of epileptic activity. Excessive calcium influx into neurons is the first step toward a seizure. The aim of the present study is to investigate whether the calcium channel blocker nimodipine has anticonvulsive effects. The left cerebral cortex was exposed by craniotomy in anaesthetized rats. An epileptic focus was produced by injection of penicillin G potassium (500 units) into the somatomotor cortex. After the epileptiform activity reached maximum frequency and amplitude; nimodipine was injected into the same area. Application of nimodipine caused an inhibition in the electrocorticograms (ECoG). Solvent alone did not affect the epileptiform activity. The results of this study indicate that nimodipine may have anticonvulsant effects. The correspondence should be addressed to M.Ö. Bostanci, E-mail: mehmetob@omu.edu.tr

Anticonvulsant effects of melatonin on penicillin-induced epileptiform activity in rats

In the present study, we investigated the effects of melatonin on penicillin-induced epileptiform activity in female Wistar rats. The left cerebral cortex was exposed by craniotomy under urethane anesthesia for the induction of epilepsy by intracortical microinjection of penicillin (200 IU) into the left sensorimotor cortex. The epileptiform activity was analyzed by electrocorticogram (ECoG). Ten minutes before the penicillin injection, 20, 40 or 80 μg of melatonin was administered intracerebroventricularly and ECoG was monitored for 1 h. Forty or 80 μg of melatonin significantly increased the latency to epileptiform activity. Furthermore, melatonin significantly decreased the frequency of spike and spike-wave activity, whereas the amplitude of spikes remained unchanged. In conclusion, data obtained from the present study suggest that melatonin suppresses penicillin-induced epileptiform activity, and it may be an endogenous anticonvulsant.

The effects of vitamin E on penicillin-induced epileptiform activity in rats

Epilepsy is a disorder characterized by recurrent seizures, which can increase the content of reactive oxygen in the brain. Active oxygen free radical scavengers such as ascorbic acid or alpha-tocopherol (vitamin E) might prevent epilepsy. A variety of animal seizure models exist which help to document the effects of vitamin E and specify its action. In this study, we have evaluated dose-dependent effect of alpha-tocopherol on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, 100, 300, or 500 mg/kg of alpha-tocopherol was administrated intramuscularly (i.m.). alpha-Tocopherol (100, 300, or 500 mg/kg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. alpha-Tocopherol of 300, or 500 mg/kg significantly decreased the frequency of epileptiform activity in the penicillin-pretreated animals. The low dose of alpha-tocopherol (100 mg/kg) did not significantly change either amplitude or frequency of epileptiform activity. alpha-Tocopherol of 500 mg/kg i.m. was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The anti-convulsant effects of alpha-tocopherol appeared 80, 60, 30 min after alpha-tocopherol injection in 300, 500, and 3 day vitamin E supplemented groups. These data indicate that alpha-tocopherol decreases the frequency of penicillin-induced epileptic activity.

Suppression of penicillin-induced epileptiform activity by Nigella sativa: Possible mediation by neurotransmitters

Nigella sativa (NS), an endogenous plant of family Ranunculaceae, exhibits a wide range of biological activity. This report explores the effect of aqueous extract of NS seeds on penicillin-(PCN-100 IU in 100 μl) induced epileptic rat model. Oral pretreatment of NS (250 mg/kg) suppressed PCN-induced seizure considerably, reduced spike-wave discharges and occurrence of generalized tonic–clonic seizures. Electroencephalographic data showed NS pretreatment to experimental animals elicited 85% abolition of high voltage spike discharges. NS pretreatment resulted in elevation of serotonin (5-HT) level and decreased dopamine (DA) level in cerebral cortex (CC), cerebellum (CB), caudate nucleus (CN) and midbrain (MB). A significant decrease in norepinephrine (NE) level was observed only in the CC. The present study suggests that chronic administration of NS protects PCN-induced generalized epilepsy by selectively altering the monoamine level in different brain regions. The seizure abolition observed in the NS pretreated rats was comparable to the anticonvulsive pattern exhibited by diazepam. The results suggest that NS has promising anticonvulsant action.

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

Leptin is an adipose tissue-derived peptide hormone, which acts as a satiety factor to reduce appetite by interactions with hypothalamic neurons. The other possible physiological functions of leptin are still unclear. In this study, we have evaluated dose-dependent effect of leptin on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorymotor cortex. Thirty minutes after penicillin injection, 1, 2 or 10 μg of leptin was administrated intracerebroventricularly (i.c.v .). Leptin (1, 2 or 10 μg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. One or two micrograms of leptin significantly increased the frequency of epileptiform activity in the penicillin-pretreated animals. The high dose of leptin (10 μg) did not significantly change either amplitude or frequency of epileptiform activity. One microgram i.c.v. leptin was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The proconvulsant effects of leptin appeared 90 min after leptin (1 and 2 μg) injection. These data indicate that leptin increases the frequency of penicillin-induced epileptic activity. We speculate that this action of leptin might suggest that leptin may be a proconvulsant substance.

Time courses of aspartate and glutamate concentrations in the focus area during penicillin induced epileptiform activity in awake rats.

1. In 16 awake rats, the time courses of cortical aspartate (ASP) and glutamate (GLU) concentrations were investigated before, during and after penicillin-induced epileptiform activity (PCN-EA). The amino acids were collected by means of the microdialysis technique from a site within the motor cortex located close to the PCN focus. PCN-EA was recorded by means of 12 cortical electrodes. 2. The median time courses of ASP and GLU concentrations demonstrated no relation to the time course of PCN-EA. In contrast, the analysis of individual time courses revealed three response types for both ASP and GLU which could not be related to specific sites within the motor cortex. 3. The ASP concentration was i) not affected by epileptiform activity (8 of 16 rats), ii) changed synchronously with the PCN-EA (3 of 16), or iii) increased transiently or in a long-lasting manner during or after disappearance of PCN-EA (5 of 16). 4. The GLU concentration was i) not effected or only slightly affected by epileptiform activity (5 of 16), ii) decreased strongly during the activity (7 of 16), or iii) increased during the epileptiform activity (4 of 16). 5. If all rats were taken into account, the overall observation was absence of a uniform correlation type between the time courses of ASP and GLU concentrations; i.e. epileptiform activity affects the time courses of ASP and GLU concentrations in an independent manner. 6. These results demonstrate that consideration of median values alone can mask significant effects of epileptiform activity on the biochemistry of the brain in individual animals. The study also shows that a consideration of individual time courses of physiological and biochemical parameters is mandatory for the understanding of basic mechanisms of epilepsy. The results support the hypothesis about the activation of neuroprotective mechanisms by epileptiform activity.

Proconvulsant effects of central and peripheral administration of L‐name on penicillin‐induced epilepsy in rats

AbstractThe effect of Nϖ‐nitro L‐arginine methyl ester (L‐NAME) on penicillin‐induced epileptiform activity was investigated in anaesthetized Wistar rats. Approximately 39.1 ± 5.7 min after penicillin G (3 million U/kg, i.p.) administration, large amplitude intermittent sharp waves appeared in the electrocorticogram. L‐NAME (60 mg/kg, i.p.) injection 30 min before penicillin G adminstration significantly reduced the latency of epileptiform activity (12.9 ± 3.2). In other groups, when the epileptiform activity reached maximum levels, administration of L‐NAME (300 μg/2 μl, i.c.v.) significantly increased the frequency of epileptic spikes, while saline and D‐NAME (Nϖ‐nitro D‐arginine methyl ester, 300 μg i.c.v.) were completely ineffective.These results suggest that L‐NAME has proconvulsant effects and NO may be an endogenous anticonvulsant substance.

Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats

The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures. Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation. Histological examination of the targeted region did not reveal signs of necrosis. These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy. In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses. However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated. The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy. These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation.

Effects of L-Arginine on Penicillin-Induced Epileptiform Activity in Rats

It has been suggested that nitric oxide (NO) is involved in the pathophysiology of epilepsy. Data are, however controversial because it is not clear whether NO has pro- or anticonvulsant effects. The aim of this study was to investigate the effects of NO on penicillin G-induced epileptiform activity. The left cerebral cortex was exposed by craniotomy in urethane-anesthetized Wistar rats. The epileptic activity was produced by intraperitoneal injection of penicillin G (3 million U/kg, i.p.). The ECoG (electrocorticogram) activity was displayed on a four-channel recorder. At 39.7 +/- 5.4 min after penicillin administration, large amplitude sharp waves appeared in the ECoG. Mean spike frequency and mean spike amplitude were calculated as 29.5 +/- 3.2/min and 865 +/- 91 microV, respectively, at the 55th min. 7-Nitroindazole (60 mg/kg, i.p.) injection 30 min before penicillin G administration significantly reduced the latency of epileptiform activity. Intracerebroventricular administration of L-arginine (300 microg/2 microl, i.c.v.) and sodium nitroprusside (100 microg/2 microl, i.c.v.) suppressed epileptiform activity. Saline (2 microl) and D-arginine (300 microg/2 microl, i.c.v.) administration into the cerebral ventricle were completely ineffective on epileptiform activity (P<0.01). These findings suggest that NO may be an endogenous antiepileptic substance.

Depressive effect of nicardipine on penicillin-induced epileptiform activity in rats

It is believed that calcium ions have very important role in the formation of epilepsy. Calcium ion flux into the cell leads to secretion of excitatory neurotransmitters. During epileptic seizures, routine balance of excitation and inhibition is altered towards the excitation. In present study, the effect of nicardipine on penicillin-induced epilepsy was investigated. The left cerebral cortex was exposed by craniotomy in anaesthetized rats. The epileptic focus was produced by injection of penicillin G potassium (500 units) into the somatomotor cortex. Microinjection of nicardipine into the same area caused an inhibition for 4-5 minutes in electrocorticograms (ECoG). The results of this study suggest that nicardipine may be an effective anticonvulsant agent in treatment of epilepsy by preventing calcium flux into the cell.

Aconitine inhibits epileptiform activity in rat hippocampal slices.

The effect of aconitine, an alkaloid neurotoxin known to bind at site 2 of the sodium channel, was investigated on epileptiform activity in hippocampal slices by use of extracellular recordings in CA1 pyramidal cell layer. Epileptiform activity was induced by bicuculline, picrotoxin, penicillin, pentylenetetrazol or by omission of magnesium from the bathing medium, respectively. In every case aconitine (0.1 and 1 microM) blocked the multiple population spikes representing the epileptiform activity. The onset of inhibition was shorter by use of an increased concentration of the epileptogenic drug. Epileptiform activity evoked by pentylenetetrazol and low magnesium was first increased by aconitine followed by a rapid inhibition, while the bicuculline-, picrotoxin-, and penicillin-induced epileptiform discharges were immediately abolished.

Time-related antiepileptic effects of the synthetic glucorticoid dexamethasone in rat hippocampal slices

The in vitro antiepileptic activity of the synthetic glucocorticoid dexamethasone (DEX) was tested in rat hippocampal slices on the CA1 epileptiform activity induced by sodium penicillin (PEN). Slice perfusion with 1 mM PEN produced within 60 min the development of a CA1 epileptiform bursting made up of an increase of the primary CA1 population spike followed by the appearance of secondary epileptiform population spikes. Slice perfusion with 100 μM DEX together with PEN (1 mM) partially prevented but did not block the expression of the CA1 epileptiform bursting as evidenced by a significant (P < 0.05) reduction of the duration of the bursting due to the epileptogenic agent. Slice perfusion with 50 μM DEX together with PEN (1 mM) failed to prevent or block the expression of the CA1 penicillin-induced epileptiform bursting. A 60 min slice pretreatment with 50–100 μM DEX followed by a slice perfusion with 50–100 μM DEX together with PEN (1 mM) prevented the expression of the CA1 epileptiform bursting. Cycloheximide (1 μM), a protein synthesis inhibitor, perfused together with DEX reverted the inhibitory effects of dexamethasone on the expression of the penicillin-induced CA1 epileptiform bursting. The results indicate that the synthetic glucocorticoid DEX presents concentration- and time-related in vitro. antiepileptic effects. In addition, the data suggest that this inhibitory effect occurs via a protein synthesis-dependent mechanism.