Additive effects of antiepileptic drugs and pentylenetetrazole on hearing

The long-term effect of three of the most widely used antiepileptic drugs at relevant doses on the hearing decline that accompanies pentylenetetrazole (PTZ)-induced experimental epilepsy was investigated here, and compared with the effect of vinpocetine (VPC), which is a drug with antiepileptic potential. For this purpose, cortical activity (monitored by the EEG) and auditory sensitivity, as indicated by brainstem auditory evoked potential (BAEP) threshold at 4 and 8 kHz tone frequencies, were determined in guinea pigs daily injected for 28 days with vehicle (control), 20 mg/kg carbamazepine (CBZ), 6 mg/kg phenytoin (PHT), 30 mg/kg valproate (VPA) or 2 mg/kg vinpocetine (VPC) before and after the administration of PTZ at a convulsing dose (100 mg/kg). Results show that all the antiepileptic drugs tested were more or less effective in preventing PTZ-induced seizures. The long-term treatment with VPC decreased the auditory threshold, whereas the long-term treatment with CBZ, PHT or VPA increased the auditory threshold to a similar extent as the convulsing agent, PTZ. The combined effects of the antiepileptic drugs and PTZ on auditory threshold were additive. Therefore, only VPC prevented the increase in the auditory threshold induced by PTZ. It is concluded that the hearing loss produced by the long-term treatment with the most commonly used antiepileptic drugs could be aggravated by the illness. The prevention exerted by VPC on the hearing decline that accompanies experimental epilepsy, along with its capacity to control seizures at low doses in this and other animal models of epilepsy, would make VPC a valid candidate for the treatment of epilepsy.     

Carnosine, a precursor of histidine, ameliorates pentylenetetrazole-induced kindled seizures in rat

Carnosine (beta-alanyl-l-histidine) has been characterized as a putative neurotransmitter. However, so far, understanding of the role of carnosine in the brain is very limited. The objective of this study was to examine the effects of carnosine on the development of pentylenetetrazol (PTZ) kindling seizures and protection against the PTZ kindled seizures in rats. Chemical kindling was elicited by repeated intraperitoneal injection of PTZ (35 mg/kg) once every 48 h until the occurrence of Stage 4-5 seizures, and the seizure activity of kindling was recorded for 30 min. In an acute PTZ challenge study, 60 mg/kg PTZ was used to induce kindled seizure. Injection of carnosine (200, 500 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latencies for myoclonic jerks, in a dose- and time-dependent manner. In the seizure development process, 500 mg/kg carnosine also significantly delayed the onset of PTZ kindled seizures. In addition, carnosine significantly reversed decreased histamine levels induced by PTZ kindled seizure in the hippocampus. These results indicate that carnosine can protect against PTZ-induced seizures in both the development of kindling and the challenge process in rats. The results suggest that carnosine might be an endogenous anticonvulsant factor in the brain and can be used as a new antiepileptic drug in future.     

Carnosine inhibits pentylenetetrazol-induced seizures by histaminergic mechanisms in histidine decarboxylase knock-out mice

In the present study, we used both histidine decarboxylase-deficient (HDC-KO) mice and wild-type (WT) mice to elucidate the possible role of carnosine in pentylenetetrazol (PTZ)-induced seizures. In the acute PTZ challenge study, PTZ (75 mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latency for myoclonic jerks in WT mice in a dose-dependent manner. The effects of carnosine (500 mg/kg) were time-dependent and reached a peak at 1 h. However, it had no significant effect on HDC-KO mice. Carnosine (500 mg/kg) also significantly elevated the thresholds in WT mice but not HDC-KO mice following intravenous (tail vein) administration of PTZ. We also found that α-fluoromethylhistidine substantially reversed the protective effects of carnosine in WT mice. In addition, carnosine pretreatment reduced the cortical EEG activity induced by PTZ (75 mg/kg, i.p.). These results indicate that carnosine can protect against PTZ-induced seizures and its action is mainly through the carnosine–histidine–histamine metabolic pathway. This suggests that carnosine may be an endogenous anticonvulsant factor in the brain and may be used as a new antiepileptic drug in the future.     

Naloxone improves impairment of spatial performance induced by pentylenetetrazol kindling in rats

The role of endogenous opioid peptides in impairment of spatial performance due to epileptogenesis was examined. Animals were kindled by repeated injections of pentylenetetrazol (PTZ) (40 mg/kg, i.p.) in the presence or absence of the opioid receptor antagonist naloxone. Naloxone in different doses (1, 5 and 10 mg/kg, i.p.) was applied 30 min before each PTZ injection. Behavioral testing was assessed 24 h and 10 days after the last injection in separate groups of animals using Morris water maze. Our results showed that PTZ-induced kindling produced a significant impairment of spatial learning and memory as compared with controls and this effect was not due to the aftereffect of repeated seizures. Naloxone pretreatment in the course of kindling had no effect on seizures development, however it caused an improvement of spatial learning and memory performance in kindled rats. It is likely that the long-lasting changes in neuronal responsiveness associated with kindling led to a defect in the processing of spatial information. These data suggest that endogenous opioid peptides released in the hippocampus during kindling are at least in part responsible for impairment of spatial performance in kindled animals.     

Ascorbate modulates pentylenetetrazol-induced convulsions biphasically

Ascorbate is an antioxidant vitamin that is found in high concentrations in the brain which seems to have neuroprotective properties in some experimental models of excitotoxic neurological disorders, including convulsive behavior and reactive species-related damage. In this study we tested whether ascorbate (30, 100 or 300 mg/kg, i.p.) protects against the convulsions, protein carbonylation and inhibition of Na(+),K(+)-ATPase activity induced by pentylenetetrazol (PTZ; 1.8 micromol/striatum), a classical convulsant agent that has been fairly used for the study of epilepsy and screening of new compounds with antiepileptic activity. The intrastriatal injection of PTZ caused convulsive behavior in a dose-dependent manner and an increase in the total protein carbonyl content of the injected striatum. However, duration of PTZ-induced convulsive episodes did not correlate with protein carbonyl content of the injected striatum. Ascorbate, at high doses (300 mg/kg), protected against PTZ-induced convulsions, protein carbonylation and inhibition of Na(+),K(+)-ATPase activity in the rat striatum, further suggesting a anticonvulsant and neuroprotective role for this vitamin. Conversely, intermediate doses of ascorbate (100 mg/kg) potentiated the duration of the convulsive episodes, but had no additive effects on protein carbonylation or Na(+),K(+)-ATPase activity inhibition induced by PTZ. Low doses of ascorbate (30 mg/kg) prevented PTZ-induced increase of total striatal carbonyl protein content, but did not alter PTZ-induced convulsions and Na(+),K(+)-ATPase activity inhibition. Collectively, these data indicate that the anticonvulsant activity of ascorbate is not related to its antioxidant action and support a dual role for this compound as a neuroprotective agent, since while it protects against PTZ-induced cellular oxidative damage, it has a biphasic effect on PTZ-induced convulsions.     

Wi-Fi decreases melatonin protective effect and increases hippocampal neuronal damage in pentylenetetrazole induced model seizures in rats

AimEpilepsy is a common brain disorder in which the seizures could cause a neuronal loss in the hippocampus. Oxidative stress has an important role in the pathology of epilepsy. Some studies indicate that Wi-Fi increases oxidative stress and suppresses antioxidant systems. The aim of this study is to investigate the effect of Wi-Fi on melatonin anticonvulsive effect and oxidative damage in pentylenetetrazole-induced epileptic seizures in rats.MethodsIn our study, we used 30 male Wistar Albino rats, 230?250 grams of the body weight. The animals were divided into five groups as control, saline (1 ml/kg/day olive oil for 30 days), Wi-Fi (12 h/day for 30 days), melatonin (10 mg/kg/day for 30 days) and melatonin + Wi-Fi (10 mg/kg/day +12 h/day for 30 days). In the thirtieth day, thirty minutes after the last drugs administration at the indicated doses, PTZ in 45 mg/kg was administered to induce epileptic seizure. The animals were observed for 30 min during the seizure stages (according to the Racine Scale) and first myoclonic jerk times (FMJ). Twenty-four hours after PTZ injection, brain tissues were removed for biochemical and histopathological evaluation. The hippocampal Cornu Ammonis (CA) 1, CA3 and DG (dentate gyrus) regions were histopathologically evaluated in terms of a neuronal damage in addition that oxidative stress markers (total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were measured in brain tissues.ResultsWi-Fi was not found to affect behavioral changes associated with epilepsy (p > 0.05). However, Wi-Fi reduced anticonvulsive and antioxidant effect of melatonin (p < 0.05). Moreover, Wi-Fi increased neuronal damage in hippocampus (p < 0.05).ConclusionWi-Fi did not directly affect epileptic seizures. Nevertheless, it inhibits the positive effects of melatonin on epilepsy and it also has negative effects on hippocampal neuronal damage. These effects of Wi-Fi may occur via oxidative pathways.     

Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression

Rodent seizure models have significantly contributed to our basic understanding of epilepsy. However, medically intractable forms of epilepsy persist and the fundamental mechanisms underlying this disease remain unclear. Here we show that seizures can be elicited in a simple vertebrate system e.g. zebrafish larvae (Danio rerio). Exposure to a common convulsant agent (pentylenetetrazole, PTZ) induced a stereotyped and concentration-dependent sequence of behavioral changes culminating in clonus-like convulsions. Extracellular recordings from fish optic tectum revealed ictal and interictal-like electrographic discharges after application of PTZ, which could be blocked by tetrodotoxin or glutamate receptor antagonists. Epileptiform discharges were suppressed by commonly used antiepileptic drugs, valproate and diazepam, in a concentration-dependent manner. Up-regulation of c-fos expression was also observed in CNS structures of zebrafish exposed to PTZ. Taken together, these results demonstrate that chemically-induced seizures in zebrafish exhibit behavioral, electrographic, and molecular changes that would be expected from a rodent seizure model. Therefore, zebrafish larvae represent a powerful new system to study the underlying basis of seizure generation, epilepsy and epileptogenesis.     

Influence of carbenoxolone on the anticonvulsant efficacy of phenytoin in pentylenetetrazole kindled rats

Abnormal synchronized neuronal discharges mediated by gap junctions have an important role in epileptic seizures. The analysis of anticonvulsant drugs acting on gap junctions is still a priority in epilepsy research. Therefore, the present study was designed to investigate the effect of carbenoxolone, a gap junction blocker, on the anticonvulsant efficacy of phenytoin in pentylenetetrazole kindled rats. Male Wistar albino rats, 14 weeks of age, were used. In the first step of the study, animals were given PTZ 35 mg/kg intraperitoneally (i.p.) three times a week until kindling was produced. Then, indwelling screw electrodes - allowing EEG monitoring of conscious rats - were implanted into the crania of the kindled rats. In this way, we were able to record EEG activity and evaluate seizure stage at the same time. In the second step of the study, the interaction between carbenoxolone (40 mg/kg i.p.) and phenytoin (60 mg/kg, i.p.) was investigated. The data analysis was performed using a one-way ANOVA with LSD post-hoc test. Total spike number and the generalized seizure duration were reduced in the carbenoxolone treated group compared to the PTZ group. Phenytoin decreased generalized seizure duration, total spike number and seizure severity score. Carbenoxolone and phenytoin have anti-seizure effects in PTZ kindled rats. There was no significant difference between the carbenoxolone + phenytoin combination and phenytoin in terms of generalized seizure duration, total spike number and seizure stage. The results indicate that carbenoxolone combined with phenytoin is not more effective than the use of these drugs alone.     

Study pharmacologic of the GABAergic and glutamatergic drugs on seizures and status epilepticus induced by pilocarpine in adult Wistar rats

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Glutamate (10 and 20 mg/kg), N-methyl-d-aspartate (NMDA, 5 and 10 mg/kg), ketamine (1.5 and 2.0 mg/kg), gabapentin (200 and 250 mg/kg), phenobarbital (50 and 100 mg/kg) and vigabatrin (250 and 500 mg/kg) were administered intraperitoneally, 30 min prior to pilocarpine (400 mg/kg, i.p.). The animals were observed (24 h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. NMDA and glutamate had pro-convulsive effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures and/or mortality. Gabapentin, vigabatrin, phenobarbital and ketamine protected against seizures and increased the latency to first seizure. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with seizures and SE because of the possibility of facility the convulsive process toxicity, SE and the mortality of adult animals in this seizures model that is similar temporal lobo epilepsy in humans.     

Effect of gabaergic, glutamatergic, antipsychotic and antidepressant drugs on pilocarpine-induced seizures and status epilepticus

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Fluoxetine (10 and 20 mg/kg), NMDA (N-methyl-D-aspartate, 10 and 20 mg/kg), amitriptyline (25 and 50 mg/kg), ketamine (0.5 and 1.0 mg/kg), gabapentin (100 and 150 mg/kg) and pimozide (10 and 20 mg/kg) were administered intraperitoneally, 30 min prior to pilocarpine (400mg/kg, s.c.). The animals were observed (24h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Fluoxetine, amitriptyline, NMDA, and pimozide had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures and/or mortality. Gabapentin and ketamine protected against seizures and reduced the latency to first seizure. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with epilepsy because of the possibility of potentiating convulsive process toxicity.     

Pharmacological studies of the opioids, mood stabilizer and dopaminergic drugs on pilocarpine-induced seizures and status epilepticus

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Morphine (0.1 and 0.2 mg/kg), SCH 23390 (0.1 and 0.2 mg/kg), haloperidol (5 and 10mg/kg) and lithium (30 and 60 mg/kg) were administered intraperitoneally (i.p.), 30 min before to pilocarpine (400 mg/kg, s.c.). The animals were observed (24 h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Morphine and haloperidol had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures, SE and/or mortality. SCH 23390 protected against seizures, increased the latency to first seizure and reduced the mortality of the animals treated with pilocarpine Theses results suggest that dopamine receptor system receptor subtypes exert opposite functions on the regulation of convulsive activity. The morphine is proconvulsant in lower doses. The opioids in high doses tested exert an action proconvulsant during the establishment of epileptic activity induce by pilocarpine. The lithium no protected the animals against seizures induced by pilocarpine and is used which a model of epilepsy associated with lower doses of pilocarpine in several studies, suggesting absence of the effect anticonvulsants in rodents.     

戊四氮点燃大鼠癫痫发作和癫痫形成过程中海马5-HT水平的变化

目的：研究戊四氮（PTZ）点燃大鼠癫痫形成过程中行为、脑电及海马5-羟色胺（5-HT）水平的变化。方法：对大鼠腹腔注射PTZ35mg／（kg·d）,观察行为变化,在不同时间点（第7、14、21、28天）,进行脑电记录,微透析取海马组织间液,活体观察24只自由活动大鼠在点燃过程和诱发发作前后脑电、海马5-HT及其代谢产物5-羟吲哚乙酸（5-HIAA）水平及其5-HT转化率（5-HIAA／5-HT）的变化。结果：开始PTZ注射后,发作潜伏期逐日缩短,发作程度逐日加重,点燃时间在10～14d。在制模过程中有一只鼠死亡。海马脑电随着发作的加重而出现癫痫波潜伏期缩短,癫痫波量增加,发作间期出现自发放电。点燃早期（第7天）,发作间期大鼠的海马5-HT水平略有升高,随着点燃时间延长,5-HT水平逐渐降低,在点燃后（第14天）维持点燃（第21、28天）5-HT水平持续下降,与点燃前5-HT水平比较,差异无显著意义（P〉0．05）;5-HT转化率在点燃过程变化差异无统计学意义;5-HIAA水平在点燃时期和维持点燃时期呈逐步降低,点燃期、维持点燃期与对照组比较差异有显著意义（P〈0．05）。结论：PTZ点燃大鼠癫痼形成过程中,在点燃前,发作间期的海马5-HT水平呈阶段性升高,点燃后,发作间期的海马5-HT水平逐渐降低;点燃后,发作间期的海马5-HT水平明显低于正常水平;随着维持点燃时间延长,发作间期的海马5一HT水平呈进行性下降。     

Characterization of the anticonvulsant profile of isonicotinic acid benzylamide in various experimental seizure models in mice

This study focused on the evaluation of anticonvulsant properties of isonicotinic acid benzylamide (iso-Nic-BZA) in numerous experimental seizure models (maximal electroshock [MES]-, bicuculline [BIC]-, pentylenetetrazole [PTZ]-, pilocarpine [PILO]-, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]-, kainic acid [KA]- and N-methyl-d-aspartic acid [NMDA]-induced seizures). Moreover, acute adverse-effect profile of the agent with respect to impairment of motor coordination was assessed in animals subjected to the chimney test. The evaluation of time-course and dose-response relationships for iso-Nic-BZA provided evidence that the compound produced the peak to maximum antielectroshock action and acute adverse effects at 5min after its systemic (i.p.) administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against maximal electroshock-induced seizures in mice and its ED(50) value was 70.6 (56.4-88.4)mg/kg. The assessment of acute adverse effects in the chimney test revealed that the agent produced acute neurotoxic effects and its TD(50) value was 135.6 (108.8-169.0)mg/kg. Additionally, iso-Nic-BZA showed the anticonvulsant activity in numerous chemically-induced seizures (AMPA-, BIC-, KA-, and PTZ-evoked clonic convulsions), remaining virtually ineffective (at doses up to 200mg/kg) in PILO- and NMDA-induced seizures in mice. Based on this study, one can conclude that iso-Nic-BZA due to the short time to peak of its maximum anticonvulsant effects (5min after its i.p. administration), deserves more attention as a potential antiepileptic drug for patients in status epilepticus.     

Strain differences in mice in the development of tolerance to the anti-pentylenetetrazole effects of diazepam

The development of tolerance to the protective effects of diazepam (4 mg/kg) against seizures induced by pentylenetetrazole (PTZ) were studied in 3 strains of mice. Significant tolerance developed to protection against myoclonic jerks induced by PTZ (90-100 mg/kg) by day 5 in Tuck No. 1 and by day 10 in C3H/HE and CD-1 mice. Tolerance developed to protection against tonic-clonic convulsions by day 10 in Tuck No. 1 mice and by day 30 in the other strains. Diazepam remained protective against tonic-clonic convulsions (but not against myoclonus) induced by threshold doses of PTZ for 30 days in all 3 strains.     

Montelukast reduces seizures in pentylenetetrazol-kindled mice

Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT₁ immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT₂ immunoreactivity only in kindled mice. CysLT₁ antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.     

Posttraining administration of pentylenetetrazol dissociates gabapentin effects on memory consolidation from that on memory retrieval process in mice

Gabapentin (GBP), an anticonvulsant drug, 10 mg/kg, i.p., but not 100 mg/kg, i.p., enhanced retention of an inhibitory avoidance task when given 20 min after training, as indicated by retention performance 48 h later. The immediate post-training administration of pentylenetetrazol (PTZ, 45 mg/kg, i.p.) impaired retention performance. The amnesic effects of the convulsant drug PTZ were not influenced by GBP at any level of doses. However, GBP 100 mg/kg, but not 10 mg/kg, delayed the latency to first clonic body seizures and decreased the duration of convulsion induced by PTZ. The enhancing effect of GBP on retention was not prevented by the opiate receptor antagonist, naltrexone (0.01 mg/kg, i.p.), which completely prevented the impairment of retention caused by PTZ. Further, naltrexone did not modify the convulsions induced by PTZ. In mice pretreated with naltrexone and that received PTZ, the administration of GBP again, enhanced retention performance during the retention test. Since previous results indicate that the amnesic action of PTZ are due to an effect on memory retrieval, the present results provide additional pharmacological evidence suggesting that GBP influenced memory consolidation and not memory retrieval of an inhibitory avoidance task in mice.     

On the anticonvulsant activity of kaurenic acid

Kaurenic acid [(-)-kaur-16-en-19-oic acid] is a diterpene isolated from the aerial parts of Espeletia semiglobulata, one of 85 species of Espeletiinae found in Venezuela. Its anticonvulsive activity was studied using two different models of experimental seizures: spinal seizures induced by sudden cooling (SSSC) in amphibians and seizures induced by pentylenetetrazol (PTZ) in mice. In SSSC, kaurenic acid (KA) inhibited the tonic hind-limb extension with an ED50 of 2.5 mg/kg. It was 4-fold more potent than known anticonvulsant drugs such as carbamazepine and phenytoin and 100-fold more potent than valproic acid. However, KA as well as valproic acid were ineffective against the clonic phase of SSSC. In the PTZ-induced seizures, KA at doses of 0.625 and 1.25 mg/kg increased the latency of seizure onset and protected against generalized clonic-tonic seizures by 45% and 65%, respectively. The sedative effects of KA had an ED50 of 8.5 mg/kg in mice and 75 mg/kg in amphibians. This work provides experimental evidence supporting the potential value of kaurenic acid as an anticonvulsive drug.     

Effect of systemic treatment with antibodies against glutamate on the seizure response of C57Bl/6 mice after pentylenetetrazole kindling

We studied the effect of single intraperitoneal injection of antibodies against glutamate on acute generalized epileptiform activity induced by intravenous injection of pentylenetetrazole in kindled C57Bl/6 mice. We found that in animals at various stages of kindling, administration of antibodies against glutamate in a dose of 25 mg/kg 1.5 h before testing increases the threshold of clonic seizures and tonic phase of seizures with lethal outcome and latency of seizure development, i.e. produces an antiepileptic effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 611–613, June, 2007     

Fructose-1,6-diphosphate inhibits seizure acquisition in fast hippocampal kindling

Inhibition of glycolytic metabolism may provide a new therapy for refractory epilepsy. Fructose-1,6-diphosphate (FDP), which inhibits glycolysis and diverts glucose into the pentose phosphate pathway, has strong inhibitory action on seizures induced by chemical convulsants. Here, we investigated the effect of FDP on a rat model of rapid hippocampal kindling. After determining the after-discharge threshold (ADT), the seizure severity and after-discharge duration (ADD) were measured to study the antiepileptogenic effects of FDP (0.5 or 1.0 g/kg i.p. for 4 days). The mRNA expression levels of the brain-derived neurotrophic factor (BDNF) and its principal receptor TrkB, which are key modulators of seizure activity, were determined in the ipsilateral hippocampus by real-time polymerase chain reaction (RT-PCR). High-dose FDP (1.0 g/kg) delayed kindling development together with shortened ADD, and high-dose treated rats also needed more kindling stimulations and more cumulative ADD to stage 4. However, it showed no significant antiepileptogenic effect at a lower dose of 0.5 g/kg. In addition, FDP attenuated BDNF and TrkB expression before and during kindling procedure; this result indicated that BDNF/TrkB signaling pathway may participate in the antiepileptogenic action of FDP. Our data demonstrates that FDP has a significant antiepileptogenic effect in kindling seizures and that it may be a potential antiepileptic drug in the future.     

Edaravone,a free radical scavenger,retards the development of amygdala kindling in rats

This study evaluated the antiepileptogenic effects of edaravone, a newly developed radical scavenger, on the amygdala kindling rats. The afterdischarge duration (ADD), AD threshold (ADT), and seizure severity in animals were measured to study the anticonvulsant effects of edaravone (2 mg/kg or 20 mg/kg i.p. for 7 days) on fully kindled seizures. Furthermore, for the study of antiepileptogenesis effects of the drug (2 mg/kg or 20 mg/kg i.p. for 7 days), not only ADD and seizure severity during kindling but also both the pre- and post-kindling ADT were measured. Edaravone neither induces nor inhibits fully kindled seizures regardless of the dose; however high-dose edaravone (20 mg/kg) retarded kindling development together with shortened ADD and elevated ADT. The present data suggest that high-dose edaravone has an antiepileptogenic drug effect for the prevention of epilepsy. However, other chronic models and clinical trials are needed to confirm the effects of edaravone on the prevention of human epilepsy.