Avian brainstem neurogenesis is stimulated during cochlear hair cell regeneration

Cyclosporin A (CsA) is known to decrease nitric oxide (NO) release in the nervous system. The present study was aimed at investigating the effects of acute administration of CsA on pentylenetetrazole (PTZ)-induced seizure threshold and latency and probable modulation of these effects by NO synthesis substrate L-arginine, and NO synthesis inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine. Moreover, the effect of CsA per se or concomitant with L-arginine on the development of PTZ-induced kindling was assessed. CsA (0.05, 1, 5, 10 and 20 mg/kg, s.c.) dose-dependently increased PTZ-induced clonic seizure threshold and the latency for onset of myoclonic jerks, clonic seizures and clonic-tonic generalized seizures following PTZ administration. L-NAME (10 and 30 mg/kg, i.p.) but not aminoguanidine (50 and 100 mg/kg, i.p.) potentiated the anticonvulsant effects of CsA (1 and 10 mg/kg). L-arginine (60, 100 and 200 mg/kg, i.p.) inhibited the anticonvulsant effects of CsA (20 mg/kg) in a dose-related manner. The inhibitory effect of L-arginine on CsA-induced alterations of seizure threshold and latency was blocked by L-NAME but not with aminoguanidine. CsA (20 mg/kg) significantly inhibited the development of PTZ kindling and decreased the seizure intensity as tested by a challenge dose of PTZ. Pretreatment with L-arginine (60 mg/kg) reversed the inhibitory effects of CsA on kindling development. It was concluded that CsA exerts some anticonvulsant properties that may be due to its inhibition of nitric oxide synthesis.     

Diphenyl diselenide and 2,3-dimercaptopropanol increase the PTZ-induced chemical seizure and mortality in mice

The aim of the present study was to evaluate the interaction between a classic GABAergic antagonist -- pentylenetetrazol (PTZ) with an organoselenium compound -- diphenyl diselenide (PhSe)(2) and with the metal chelating agent -- 2,3 dimercaptopropanol (BAL). Mice were pre-treated with 150 micromol/kg (PhSe)(2) or BAL (250, 500 or 1000 micromol/kg) before treatment with PTZ. Pre-treatment with (PhSe)(2) reduced the latency for PTZ-induced seizure at doses of 40 and 60 mg/kg and cause a decrease in the latency for PTZ-induced death at the dose of 60 mg/kg. However, treatment with PTZ at dose of 80 mg/kg was not affected by (PhSe)(2) pre-treatment. Pre-treatment with BAL reduced the latency for PTZ-induced seizure at doses of 40 and 50 mg/kg. In addition, the latency for PTZ-induced death at the dose of 40 mg/kg was decreased significantly by pre-treatment with all doses of BAL. At the dose of 50mg/kg, a significant decrease in the latency for death occurred only in mice pre-treated with 500 and 1000 micromol/kg of BAL. Our results indicate that the PTZ-induced chemical seizures and mortality was enhanced by (PhSe)(2) and BAL. These results indicated that (PhSe)(2) and BAL interact with PTZ possibly by modulating the GABAergic system.     

Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding

Experiments using male CD1 mice were carried out to investigate the effects of subchronic (daily administration for 8 days) pretreatments with drugs enhancing GABAergic transmission (diazepam, 10 mg/kg, ip; gabapentin, 100 mg/kg, po; or vigabatrin, 500 mg/kg, po) on pentylenetetrazol (PTZ)-induced seizures, 24 h after the last injection. Subchronic administration of diazepam reduced latencies to clonus, tonic extension and death induced by PTZ. Subchronic vigabatrin produced enhanced latency to the first clonus but faster occurrence of tonic extension and death induced by PTZ. Subchronic gabapentin did not modify PTZ-induced seizures. Autoradiography experiments revealed reduced benzodiazepine receptor binding in several brain areas after subchronic treatment with diazepam or gabapentin, whereas subchronic vigabatrin did not induce significant receptor changes. The present results indicate differential effects induced by the subchronic administration of diazepam, vigabatrin, and gabapentin on the susceptibility to PTZ-induced seizures, benzodiazepine receptor binding, or both.     

Traxoprodil decreases pentylenetetrazol-induced seizures

Polyamines, including spermidine, facilitate seizures by positively modulating N-methyl-d-aspartate receptors (NMDAr). Although NMDAr antagonists decrease seizures, it remains to be determined whether traxoprodil, a selective antagonist at the NR2B subunit of the NMDAr, decreases seizures and whether spermidine facilitates pentylenetetrazol (PTZ)-induced seizures. Adult male Wistar rats were injected in the lateral ventricle with 0.9% NaCl (1μl, i.c.v.), spermidine (0.02, 0.2 or 2nmol/site, i.c.v.) or traxoprodil (0.2, 2 or 20nmol, i.c.v.) and with PTZ (35 or 70mg/kg, i.p.). The effect of orally administered traxoprodil (60mg/kg, p.o.) on seizures was also investigated. Latencies to clonic and generalized seizures, as well the total time spent in seizures were recorded by behavioral and electrographic methods (EEG). Spermidine (2nmol/site; i.c.v.) facilitated the seizures induced by a sub-threshold dose of PTZ (35mg/kg; i.p.), but did not alter seizure activity induced by a convulsant dose of PTZ (70mg/kg; i.p.). Traxoprodil (20nmol i.c.v.) increased the latency to generalized tonic-clonic seizures induced by PTZ (70mg/kg; i.p.). Traxoprodil (60mg/kg, p.o.) increased the latency to clonic and generalized seizures, and decreased the total time spent in seizures. These results support the role for the NR2B subunit in PTZ-induced seizures.     

NITRIC OXIDE INVOLVEMENT IN SEIZURES ELICITED BY PENTYLENTETRAZOL AND SEX DEPENDENCE

It has been known that susceptibility to some types of epilepsy is affected by sex. In addition, the role of NO in epileptogenesis is still unclear; NO has been suggested to be either an anticonvulsive or a proconvulsive agent. In an attempt to elucidate both the role of NO and sex differences in sensitivity to seizures, male and female Wistar rats were treated intraperitoneally (i.p.) by pentylentetrazol (PTZ)(80 mg/kg) and by a nitric oxide synthase(NOS) inhibitor N-omega-nitro-L-arginine-mthylester(L-NAME)(50mg/kg) and a NO precursor sodium-nitroprusside(SNP)(2.5mg/kg)- applied 15 min. before PTZ injection. Latency, frequency, severity, and duration of generalized clonic and clonic-tonic convulsions were recorded. Furthermore, alterations in severity, latency, frequency, and duration of convulsions were observed to correlate with NO. Both sexes, injected with PTZ, showed repetitive seizure patterns. Seizures were found to be more severe in females. L-NAME and SNP pretreatment produced paradoxical effects on PTZ-induced seizures in both sexes. L-NAME completely prevented PTZ-induced seizures in male rats, whereas increased severity, frequency, duration, and significantly shortened the latency in female rats. Unexpectedly, SNP increased convulsion severity, frequency, duration, and shortened latencies in male, whereas it decreased convulsion severity, frequency, and duration and prolonged latency in females. These results indicate that endogenous NO is involved in the regulation of convulsive action suggesting a role depending on sex.     

Nitric oxide involvement in seizures elicited by pentylentetrazol and sex dependence

It has been known that susceptibility to some types of epilepsy is affected by sex. In addition, the role of NO in epileptogenesis is still unclear; NO has been suggested to be either an anticonvulsive or a proconvulsive agent. In an attempt to elucidate both the role of NO and sex differences in sensitivity to seizures, male and female Wistar rats were treated intraperitoneally (i.p.) by pentylentetrazol (PTZ)(80 mg/kg) and by a nitric oxide synthase(NOS) inhibitor N-omega-nitro-L-arginine-mthylester(L-NAME)(50mg/kg) and a NO precursor sodium-nitroprusside(SNP)(2.5mg/kg)- applied 15 min. before PTZ injection. Latency, frequency, severity, and duration of generalized clonic and clonic-tonic convulsions were recorded. Furthermore, alterations in severity, latency, frequency, and duration of convulsions were observed to correlate with NO. Both sexes, injected with PTZ, showed repetitive seizure patterns. Seizures were found to be more severe in females. L-NAME and SNP pretreatment produced paradoxical effects on PTZ-induced seizures in both sexes. L-NAME completely prevented PTZ-induced seizures in male rats, whereas increased severity, frequency, duration, and significantly shortened the latency in female rats. Unexpectedly, SNP increased convulsion severity, frequency, duration, and shortened latencies in male, whereas it decreased convulsion severity, frequency, and duration and prolonged latency in females. These results indicate that endogenous NO is involved in the regulation of convulsive action suggesting a role depending on sex.     

Effects of acute inhibition of fatty acid oxidation on latency to seizure and concentrations of beta hydroxybutyrate in plasma of rats maintained on calorie restriction and/or the ketogenic diet

The present study was designed to evaluate the effects of acute inhibition of fatty acid oxidation on plasma levels of beta hydroxybutyrate and latency to PTZ-induced seizures in ad libitum- (AL), calorie-restricted normal rodent chow- (CR), and calorie-restricted ketogenic diet (KD)-fed young rats. Young (day 23) Sprague-Dawley rats were fasted for 8 h and then fed their respective diets for 21 days. On day 21 of the diet rats in each group received either saline or the fatty acid oxidation inhibitor mercaptoacetate (MA; 46 mg/kg intraperitoneally (i.p.). Two hours later, all rats received pentylenetetrazole (PTZ; 10 mg/kg; i.p.) every 10 min until seizure onset. Results demonstrated that KD-fed rats had the longest (P<0.05) latency to PTZ-induced seizures. KD-fed rats administered an acute dose of MA had lower (P<0.01) levels of beta hydroxybutyrate in plasma and shorter latency to PTZ-induced seizures compared with control KD-fed rats. However, there was not a significant positive correlation (P>0.10) between plasma beta hydroxybutyrate and latency to seizure, suggesting that beta hydroxybutyrate may be indirectly involved in the antiseizure effects of the KD. Fatty acid oxidation inhibition represents an experimental manipulation that may allow for more precise establishment and evaluation of levels of beta hydroxybutyrate in plasma necessary for antiseizure effects of the KD.     

The neuronal excitability time-dependently changes after lipopolysaccharide administration in mice: possible role of cyclooxygenase-2 induction

The parameters of pentylenetetrazol (PTZ)-induced seizures have been evaluated at various time intervals after lipopolysaccharide (LPS; Escherichia coli O111:B4, 100 microg/kg, i.p.) administration in mice. A proconvulsant effect occurred 4h after LPS injection with decreased seizure latency and enhanced seizure intensity. In contrast, the incidence of seizures was reduced 18 h after LPS injection. There were no significant alterations on seizure parameters 2, 8, 12, and 24h after LPS treatment. SC-58236, a selective cyclooxygenase (COX)-2 inhibitor (20 or 40 mg/kg, s.c.) treatment alone had no effect on PTZ-induced seizures, but reversed the antiseizure activity observed 18 h after LPS injection. However, SC-58236 treatment partially restored the proconvulsant changes that were observed 4h after LPS administration. On the other hand, COX-1-selective inhibitor valeryl salicylate (20 or 40 mg/kg, s.c.) itself facilitated PTZ-induced seizures. Thus, it was not possible to evaluate the effects of valeryl salicylate on the excitability changes after LPS injection. These results indicate that the parameters of PTZ-induced seizures change time-dependently after LPS treatment, in which proconvulsant and anticonvulsant states could be seen in a sequence. It seems that COX-2 isoenzyme may be involved in the neuronal excitability changes due to LPS.     

Intranasal pitavastatin attenuates seizures in different experimental models of epilepsy in mice

This study was carried out to evaluate the effect of intranasal pitavastatin (PVS) on pentylenetetrazole (PTZ)-induced seizures, increasing current electroshock (ICES) seizures, and status epilepticus in mice. Intranasal PVS, 0.5 and 1.0 mg/kg, showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control; however, the effects were dose-dependent and were more significant at higher dose. Further, intranasal PVS (1.0 mg/kg) but not intravenous PVS (50.0 mg/kg) showed effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal PVS (1.0 mg/kg), thus making it a prospective therapeutic approach for acute seizures and status epilepticus.     

Electrophysiological study of tianeptine, a new enhancer of serotonin uptake with antidepressant activity

Tianeptine is a clinically effective antidepressant, not chemically related to classical tricyclic compounds. Its mechanism of action preferentially involves central serotoninergic transmissions, by increasing uptake after acute and chronic administration in rat brain and platelets and in human platelets. We studied the effects of tianeptine on three currently used electrophysiological methods: Ro4-1284 induced PGO waves in the cat, neocortical EEG activity in the acute rat preparation and sleep-wakefulness modifications in chronically implanted rats. Density of Ro4-1284 induced PGO waves was reduced by tianeptine, the minimal effective dose being 2 mg.kg-1i.v. (ED50 = 2.9 mg.kg-1i.v.). In acute rat preparation, the low voltage fast waves basal EEG pattern was not modified by tianeptine in a dose range of 1.25 to 20 mg.kg-1i.p. Higher dosage (25 mg.kg-1i.p.) induced high amplitude episodes with few or no delta waves. Low doses which did not apparently modify acute EEG have been tested on sleep-wakefulness cycle in implanted rats. Tianeptine, after single administration, did not modify sleep states up to 2.5 mg.kg-1i.p. An increased wakefulness was observed during the first hour after 5-10 mg.kg-1i.p., afterwards sleep states returned to control values up to 12 h. A subsequent 12 h recording performed 24 h after treatment did not show any change compared to pretreatment baseline. After sub-chronic administration (2.5 mg.kg-1i.p./day, 9 days) no change was observed in sleepwake pattern during or after cessation of treatment. Tianeptine EEG profile is radically different from those usually induced by classical tricyclic antidepressants.     

Inhibitory effects of powerline-frequency (60-Hz) magnetic fields on pentylenetetrazol-induced seizures and mortality in rats.

The possibility that exposure to powerline frequency (60-Hz) magnetic fields might affect the form or intensity of epileptic seizures, induced by administration of pentylenetetrazol (PTZ) in rats, was examined. Male adult rats were exposed to either 60-Hz magnetic fields with intensities of up to 1.85 gauss (185 microT) or to a sham field condition, for 1 h prior to injections of PTZ (45-75 mg/kg). The subsequent seizures were monitored and recorded on videotape and any subsequent mortalities were noted. Exposure to 60-Hz magnetic fields prior to administration of PTZ was found to significantly (P less than 0.005) reduce the lethality of the drug-induced seizures. The LD50 for the sham-exposed group was 65.88 mg/kg, whereas for the 60-Hz magnetic field-exposed rats, the LD50 was 85.33 mg/kg. In some experiments exposure to the 1.0 and 1.5 gauss magnetic fields also produced significant (P less than 0.05) reductions in seizure durations. These findings suggest that acute exposure to low intensity 60-Hz magnetic fields has an inhibitory effect on the lethality and expression of PTZ-induced seizures in rats. Some possible mechanisms, which could account for these observed effects of magnetic field exposure on seizures, are discussed.     

Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid

PURPOSE: The purpose of this study was to determine whether N-palmitoylethanolamide (PEA), a putative endocannabinoid, would be effective against kindled amygdaloid seizures. For a comparison with earlier work, we also tested the effectiveness of PEA against pentylenetetrazol (PTZ)-induced convulsions. METHODS: Kindling electrodes were implanted bilaterally in the amygdala in 32 Long-Evans rats. After the kindling of generalized (stage 5) seizures, the effects of PEA administration [i.p.; 1, 10, 100 mg/kg in dimethylsulfoxide (DMSO)] were evaluated for anticonvulsant activity. PEA (40 mg/kg, i.p. in DMSO) also was tested for anticonvulsant activity against PTZ-induced convulsions (75 mg/kg, i.p.). RESULTS: After i.p. administration of PEA, kindled rats displayed an increased latency to clonus at the 1-mg/kg dose. No other dose-dependent effects were noted. When tested against PTZ-induced convulsions, PEA protected against tonic convulsions and prolonged the latency between convulsive episodes. CONCLUSIONS: PEA produces antiepileptic effects, but does not completely suppress seizures. The mechanism of action of PEA remains to be defined.     

Tolerance to pentylentetrazol-induced convulsions and protection of cerebrovascular integrity by chronic nicotine

The authors' previous studies have shown that in nicotine-induced seizures sensitivity was decreased and blood-brain barrier (BBB) disruption was prevented as a consequence of nicotine pretreatment. This study aimed to investigate the possible protective actions of nicotine on cerebrovascular permeability and seizures induced by pentylentetrazol (PTZ) injection. Cerebrovascular effects of nicotine were evaluated by measuring the permeability changes of BBB using Evans-Blue (EB) dye and specific gravity (SG), which indicates brain water and protein content. The experiments were carried out on Wistar rats. Animals were randomly divided into two groups. Convulsions were induced by injection of PTZ (80 mg/kg i.v.) in rats either pretreated with nicotine daily with a low dose of 0.8 mg/kg day for 21 days or injected with a single dose of 6 mg/kg mecamylamine. The same procedures were followed in control rats with the exception that they were injected only with saline. PTZ injection caused tonic-clonic convulsions and increased the EB dye leakage and specific gravity values in saline-injected control rat brains. Daily injection of nicotine lessened the intensity of seizures. These were accompanied by marked decreases in both the leakage of EB and brain water content. Acute administration of a nAChR antagonist mecamylamine significantly increased seizure latency and decreased the duration of seizures. Thereby, mecamylamine reduced the EB leakage and water content in most brain regions. These results indicate that development of tolerance to PTZ convulsions can be produced by chronic nicotine administration in rats. The mechanism for this effect currently needs clarification. Moreover, the data also suggest that cholinergic activity may account for occurrence of PTZ-induced convulsions.     

TOLERANCE TO PENTYLENTETRAZOL-INDUCED CONVULSIONS AND PROTECTION OF CEREBROVASCULAR INTEGRITY BY CHRONIC NICOTINE

The authors' previous studies have shown that in nicotine-induced seizures sensitivity was decreased and blood-brain barrier (BBB) disruption was prevented as a consequence of nicotine pretreatment. This study aimed to investigate the possible protective actions of nicotine on cerebrovascular permeability and seizures induced by pentylentetrazol (PTZ) injection. Cerebrovascular effects of nicotine were evaluated by measuring the permeability changes of BBB using Evans-Blue (EB) dye and specific gravity (SG), which indicates brain water and protein content. The experiments were carried out on Wistar rats. Animals were randomly divided into two groups. Convulsions were induced by injection of PTZ (80 mg/kg i.v.) in rats either pretreated with nicotine daily with a low dose of 0.8 mg/kg day for 21 days or injected with a single dose of 6 mg/kg mecamylamine. The same procedures were followed in control rats with the exception that they were injected only with saline. PTZ injection caused tonic-clonic convulsions and increased the EB dye leakage and specific gravity values in saline-injected control rat brains. Daily injection of nicotine lessened the intensity of seizures. These were accompanied by marked decreases in both the leakage of EB and brain water content. Acute administration of a nAChR antagonist mecamylamine significantly increased seizure latency and decreased the duration of seizures. Thereby, mecamylamine reduced the EB leakage and water content in most brain regions. These results indicate that development of tolerance to PTZ convulsions can be produced by chronic nicotine administration in rats. The mechanism for this effect currently needs clarification. Moreover, the data also suggest that cholinergic activity may account for occurrence of PTZ-induced convulsions.     

Mirtazapine does not affect pentylenetetrazole- and maximal electroconvulsive shock-induced seizures in mice

Mirtazapine is an antidepressant exhibiting both noradrenergic and serotonergic activity. We have investigated the effects of mirtazapine on pentylenetetrazole (PTZ)- and maximal electroconvulsive shock (MES)-induced seizures in mice. Mirtazapine (1.25-20mg/kg) or saline was administered, and locomotor activity was evaluated for 30 min. One hour after administration of mirtazapine (1.25-5mg/kg) or saline, PTZ (80 mg/kg) was injected intraperitoneally into the mice. Immediately afterward, times of onset of the first myoclonic jerk (FMJ), generalized clonic seizures (GCS), and tonic extension (TE) were recorded. In the MES groups, we used the MES protocol to induce convulsions characterized by tonic hindlimb extension. Similarly, 1h after mirtazapine or saline administration, an electroshock was evoked by ear-clip electrodes to induce convulsion. Mirtazapine, at 10 and 20 mg/kg, depressed locomotor activity. Doses of 1.25-5mg/kg had no significant effect on the time of onset of FMJ, GCS, or TE induced by PTZ; on the duration of GCS and TE; or on the latency to reinstatement of the righting reflex after MES administration. Our results suggest that mirtazapine neither aggravates nor alleviates PTZ- or MES-induced seizures in mice.     

Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats

The effects of intraperitoneal and methyl ester, specific inhibitors of nitric oxide (NO) synthase, were examined on the pentylenetetrazol (PTZ)-induced seizures in rats. The incidence and latency for the onset of myoclonic jerks, clonic seizures, and tonic generalized extension were observed as specific parameters among PTZ-induced seizures. Both drugs preferentially suppressed the tonic generalized extension and prolonged the latency for the onset of each parameter, suggesting NO has a significant effect on the PTZ-induced seizure.     

Behavioral characterization of pentylenetetrazol-induced seizures in the marmoset

This study was designed to characterize seizures induced with pentylenetetrazol (PTZ) in marmosets. Thirteen adult marmosets (Callithrix sp.) received 20, 30, or 40 mg/kg of PTZ intraperitoneally. PTZ caused all animals to switch their natural behavioral repertoire to early convulsive behavior. Seizure scores were low at lower PTZ doses, whereas the highest dose of PTZ led to seizure scores IV and V (according to Racine's scale) in 69% of animals. To further characterize the model we performed a preliminary evaluation of the efficacy of three antiepileptic drugs: phenobarbital, phenytoin, and carbamazepine. Phenobarbital prevented PTZ-induced seizures in 100% of trials. As expected, phenytoin and carbamazepine were not effective against PTZ-induced seizures. The present study describes the PTZ model of seizures in marmosets with a drug-response profile similar to that of the rodent model, thus bringing to a well-known model (PTZ in rodents) the complexity of a nonhuman primate brain.     

Role of nitric oxide in pentylenetetrazol-induced seizures: age-dependent effects in the immature rat

PURPOSE: Seizure susceptibility and consequences are highly age dependent. To understand the pathophysiologic mechanisms involved in seizures and their consequences during development, we investigated the role of nitric oxide (NO) in severe pentylenetetrazol (PTZ)-induced seizures in immature rats. METHODS: Four cortical electrodes were implanted in 10-day-old (P10) and 21-day-old (P21) rats, and seizures were induced on the following day by repetitive injections of subconvulsive doses of PTZ. The effects of NG-nitro-l-arginine methyl ester (l-NAME; 10 mg/kg) and 7-nitroindazole (7NI; 40 mg/kg), two NO synthase (NOS) inhibitors, and l-arginine (l-arg; 300 mg/kg), the NOS substrate, were evaluated regarding the mean PTZ dose, seizure type and duration, and mortality rate. RESULTS: At P10, the postseizure mortality rate increased from 18-29% for the rats receiving PTZ only to 100% and 89% for the rats receiving l-NAME and 7NI, respectively; whereas l-arg had no effect. Conversely, at P21, NOS inhibitors did not affect the 82-89% mortality rate induced by PTZ alone, whereas l-arg decreased the mortality rate to 29%. In addition, all NO-related drugs increased the duration of ictal activity at P10, whereas at P21, l-arg and l-NAME affected the first seizure type, producing clonic seizures with l-arg and tonic seizures with l-NAME. CONCLUSIONS: The relative natural protection of very immature rats (P10) against PTZ-induced deaths could be linked to a high availability of l-arg and, hence, endogenous NO. At P21, the modulation of seizure type by NO-related compounds may be related to the maturation of the brain circuitry, in particular the forebrain, which is involved in the expression of clonic seizures.     

Study of Antiepileptic Effect of Extracts from Acorus tatarinowii Schott

Summary:  Purpose: To study the antiepileptic properties of extracts from rhizomes of Acorus tatarinowii Schott (ATS).
Methods: The decoction and volatile oil were extracted from rhizomes of ATS by traditional decocting and supercritical CO₂ fluid extraction (SFE-CO₂) methods. Maximal electroshock (MES), pentylenetetrazol (PTZ) maximal seizure, and prolonged PTZ kindling models were used to test their anticonvulsive properties. The γ-aminobutyric acid (GABA) immunohistochemical reaction (IR) was used to study GABAergic neuron changes in the PTZ kindling model and the effects of treatment.
Results: Both decoction (dose; 10–20 g/kg) and volatile oil (1.25 g/kg) of ATS decreased the convulsive rate significantly in the MES model. Decoction of ATS was shown to be effective in the PTZ model with both decreased convulsive and mortality rates. The volatile oil of ATS failed to prevent seizures in the dose range tested, although prolonged seizure latency and decreased mortality were found at a dose of 1.25 g/kg. In the PTZ kindling model, GABA-IR neurons decreased obviously compared with the normal group. In the groups treated with the decoction and volatile oil, the seizure intensity decreased significantly after treatment. Increased GABA-IR neurons also were found when compared with PTZ kindling controls. Morphologic observation also showed that GABA-IR neuron damage was less severe in the drug-treated groups.
Conclusions: Both decoction and volatile oil extracted from the rhizome of Acorus tatarinowii Schott have anticonvulsive effects. The volatile oil is shown to be less effective for PTZ-induced convulsions. Both extracts can prevent convulsions as well as convulsion-related GABAergic neuron damage in the brain in the prolonged PTZ kindling model.     

Anticonvulsant effect of retigabine during postnatal development in rats

Retigabine is a new-generation antiepileptic drug that exerts therapeutic action through the activation of KCNQ channel dependent M-type potassium currents. While retigabine has been extensively studied in adult animals using a wide variety of seizure models, its effects in developing animals have not been examined. There has only been one previous report of retigabine efficacy in juvenile rats (Mazarati et al., 2008), which examined efficacy against kindled seizures and did not examine ages younger than postnatal day (P) 14. To determine the efficacy of retigabine during brain development we pretreated rats with retigabine (0-30 mg/kg) at three ages corresponding to the neonatal period through late childhood/early adolescence (i.e., P7, P14, or P25). Seizures were induced 30 min later using a chemoconvulsant (pentylenetetrazol, PTZ) model, which has been widely used to determine anticonvulsant efficacy of many other antiepileptic drugs in neonatal animals. In a dose and age-dependent manner, retigabine reduced the severity of PTZ evoked seizures, increased the latency to seizure onset, and decreased the incidence of full maximal seizures. The minimum effective dose was found to be 5mg/kg for P7 animals, 2.5mg/kg for P14 animals, and 1mg/kg for P25 animals. These findings allow a direct comparison between retigabine and previously studied antiepileptic drugs against PTZ seizures during development, and provide the first report of the effective dose range of retigabine in neonatal animals.