Pentylenetetrazole-induced Seizures Research Articles

Cellular responses to recurrent pentylenetetrazole-induced seizures in the adult zebrafish brain

A seizure is a sustained increase in brain electrical activity that can result in loss of consciousness and injury. Understanding how the brain responds to seizures is important for development of new treatment strategies for epilepsy, a neurological condition characterized by recurrent and unprovoked seizures. Pharmacological induction of seizures in rodent models results in a myriad of cellular alterations, including inflammation, angiogenesis, and adult neurogenesis. The purpose of this study is to investigate the cellular responses to recurrent pentylenetetrazole seizures in the adult zebrafish brain. We subjected zebrafish to five once-daily pentylenetetrazole-induced seizures and characterized the cellular consequences of these seizures. In response to recurrent seizures, we found histologic evidence of vasodilatation, perivascular leukocyte egress and leukocyte proliferation suggesting seizure-induced acute CNS inflammation. We also found evidence of increased proliferation, neurogenesis, and reactive gliosis following pentylenetetrazole-induced seizures. Collectively, our results suggest that the cellular responses to seizures in the adult zebrafish brain are similar to those observed in mammalian brains.

The Effects of Hydroalcoholic Extract of Pinus eldarica on Hippocampal Tissue Oxidative Damage in Pentylenetetrazole-Induced Seizures in Rat

Background: Brain tissues oxidative damage has been proposed to occur as a result of epileptic seizures. With respect to the antioxidant effects of Pinus eldarica (P. eldarica), the impacts of a hydroalcoholic extract of the plant on the brain tissues oxidative damage taking after seizures induced by Pentylenetetrazole (PTZ) was investigated in rats. Methods: The rats were divided into 6 groups and treated: (1) Control(saline); (2) PTZ (100 mg/kg, i.p.), [3-6] four doses including 20, 50, 200 and 500 mg/kg of P. eldarica extract (Ext 20, Ext 50, Ext 200, Ext 500) 30 min before PTZ injection. Latencies to the first Minimal Clonic (MCS) and Generalized Tonic-Clonic (GTCS) seizures were recorded. The hippocampal tissues were then collected for biochemical measurements. Results: The extract non-significantly postponed both the MCS and GTCS onsets. PTZ- induced seizure increased Malondialdehyde (MDA) (P<0.001) concentration while, diminished thiol contents (P<0.01) of hippocampal tissues. Pretreatment with 200 mg of the extract diminished MDA level in the hippocampal tissues compared to the PTZ group (P<0.001). Both 50 and 200 mg/kg of the extract improved thiol concentration in the hippocampal tissues (p<0.01). Conclusion: The present study demonstrated that the extract of P. eldarica possess protective effects against hippocampal tissues oxidative damage in PTZ- induced seizure model.

Protection Against Electroshock- and Pentylenetetrazol-induced Seizures by the Water Extract ofRehmannia glutinouscan be Mediated through GABA Receptor-chloride Channel Complexes

Epilepsy is a brain disorder that affects millions of people worldwide. It is characterized by recurrent and unpredictable seizures that are usually controlled with antiepileptic/anticonvulsive drugs. However, most antiepileptic drugs produce various side effects such as tolerance and sedation. Thus, there is a growing interest for alternative anticonvulsive drugs, preferably from natural or herbal sources. In this study, we evaluated the anticonvulsive effects of Rehmannia glutinosa (RG). The anticonvulsive effect of RG extract was evaluated using electroshock- and chemical-induced seizure tests in mice. To identify its probable mechanism of action, the effects of RG extract on Cl- influx was measured in vitro. We found that RG extract has anticonvulsive effects against electroshock-induced seizures, as indicated by an increased seizure threshold in mice. The RG extract also decreased the percentage of seizure responses induced by the GABAergic antagonist, pentylenetetrazole. These results suggest that the anticonvulsive effects of RG extract are mediated through a GABAergic mechanism. In support of this mechanism, our in vitro test showed that RG extract increases intracellular Cl- influx. Furthermore, RG extract did not show sedative and/or muscle relaxant effects in the open-field and rota-rod tests. Altogether, these results confirm that RG extract could be a herbal anticonvulsant and a potential alternative for clinical use.

Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats

Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats (n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals (p = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses (p = 0.71) nor due to the delay after the last stimulation dose (p = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200 μs, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

<b>Protective effects of ethanolic extract from the red algae <i>Amansia multifida</i> on experimental inflammation, nociception and seizure experimental models

This study aimed to investigate the EEAm effect in mice models of nociception, inflammation and in behavioral tests evaluating the central nervous system. EEAm had inhibitory effects in the following tests: acetic acid-induced writhing (78%); formalin (62% - inflammatory phase); open field (46%). EEAm increased the nociceptive latency (56%) in tail flick test and increased the death-latency by 36% in the pentylenetetrazole-induced seizure model. Moreover, EEAm inhibited paw edema (82%) and peritonitis (45%) induced by carrageenan. In conclusion, EEAm presents antinociceptive, anti-inflammatory and anticonvulsant effects involving peripheral and central-acting mechanisms in mice.

Gastrodin Attenuates Pentylenetetrazole-Induced Seizures by Modulating the Mitogen-Activated Protein Kinase-Associated Inflammatory Responses in Mice.

Gastrodin, the major component isolated from the rhizome of the Chinese traditional medicinal herb Gastrodia elata ("Tianma"), has a long history in the treatment of epilepsy and other neurological disorders. However, the molecular mechanisms are not clear. Here, we found that gastrodin ameliorated pentylenetetrazole (PTZ)-induced epileptic seizures with improvement of the electroencephalographic pattern in mice. Further studies demonstrated that gastrodin decreased the levels of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α while increasing interleukin-10, an anti-inflammatory cytokine in the brain. Furthermore, gastrodin attenuated the PTZ-induced microglial activation along with inhibition of mitogen-activated protein kinases, cAMP response element binding protein, and NF-κB. Our data suggest that gastrodin attenuates seizures by modulating the mitogen-activated protein kinase-associated inflammatory responses.

Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid.

BackgroundEpidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model.MethodsPregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo).ResultsTwo subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals.DiscussionPrenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors.

Dextrometrophan (DM), widely used as an antitussive, has recently generated interest as an anticonvulsant drug. Some effects of dextrometrophan are associated with alterations in several pathways, such as inhibition of nitric oxide synthase (NOS) enzyme and N-methyl d-aspartate (NMDA) receptors. In this study, we aimed to investigate the anticonvulsant effect of acute administration of dextrometrophan on pentylenetetrazole (PTZ)-induced seizures and the probable involvement of the nitric oxide (NO) pathway and NMDA receptors in this effect. For this purpose, seizures were induced by intravenous PTZ infusion. All drugs were administrated by intraperitoneal (i.p.) route before PTZ injection. Our results demonstrate that acute DM treatment (10-100mg/kg) increased the seizure threshold. In addition, the nonselective NOS inhibitor L-NAME (10mg/kg) and the neural NOS inhibitor, 7-nitroindazole (40mg/kg), at doses that had no effect on seizure threshold, augmented the anticonvulsant effect of DM (3mg/kg), while the inducible NOS inhibitor, aminoguanidine (100mg/kg), did not affect the anticonvulsant effect of DM. Moreover, the NOS substrate l-arginine (60mg/kg) blunted the anticonvulsant effect of DM (100mg/kg). Also, NMDA antagonists, ketamine (0.5mg/kg) and MK-801 (0.05mg/kg), augmented the anticonvulsant effect of DM (3mg/kg). In conclusion, we demonstrated that the anticonvulsant effect of DM is mediated by a decline in neural nitric oxide activity and inhibition of NMDA receptors.

A microdialysis and enzymatic reactor sensing procedure for the simultaneous registration of online glutamate measurements at high temporal resolution during epileptiform activity.

Glutamate measurement in microdialysis samples has primarily been determined using HPLC methods, and several attempts have been made to establish a relationship between this neurotransmitter and EEG activity during altered brain function, such as epilepsy. However, classic microdialysis methods lack high temporal resolution. In this study, a new alternative is proposed to improve the time resolution and thus obtain a better understanding of the dynamics of Glu and its relationship with epileptiform activity. A new setup was designed to measure Glu online in microdialysates using enzymatic reactors and fluorescence detection. In this study, we performed EEG recordings and Glu measurements simultaneously in the hippocampus to establish their relationship with the epileptiform events that are induced by pentylenetetrazole in intact and epileptic rats. Basal Glu levels in intact and animals with spontaneous seizures were not significantly different. However, a significant increase in Glu levels was detected during the first pentylenetetrazole-induced seizure in both groups. EEG analysis showed that the amplitude of epileptiform activity was higher in rats with spontaneous seizures and that the frequency of this activity did not change. The results showed that this method can be used to determine Glu changes at high temporal resolution and that these changes can be related to seizure activity. In addition, this method can also be used to measure other neurotransmitters that generate fluorescent derivatives. Moreover, this new technique has the following advantages compared with classical neurochemical methods: easy setup, low training requirements, no need for separation, rapidity, and the experimental data can be obtained and analysis performed in a single session.

Anticonvulsant activity of the antidepressant drug, tianeptine, against pentylenetetrazole-induced seizures mitigates cognitive impairment in rats.

Treatment of depression, a common comorbidity in patients with epilepsy, is restricted as certain antidepressants are considered to be proconvulsants. In contrast, anticonvulsant effects have been reported with some antidepressants. In the present study, the effect of tianeptine, an antidepressant, was evaluated against pentylenetetrazole (PTZ)-induced seizures, cognitive impairment and oxidative stress in rats. Tianeptine was administered in three doses (20, 40 and 80 mg/kg) 30 min before PTZ (60 mg/kg, intraperitoneally). MK801, an N-methyl-D-aspartate antagonist, and naloxone, an opioid receptor antagonist, were administered with tianeptine to evaluate the involvement of N-methyl-D-aspartate and opioid receptors, respectively. Morris water maze, elevated plus maze and passive avoidance tests were performed for behavioural assessment. Brain malondialdehyde and reduced glutathione levels were estimated as markers of oxidative stress. Tianeptine showed dose-dependent protection against PTZ seizures. Coadministration of tianeptine with MK801 potentiated the anticonvulsant effect of tianeptine. The protective effect of tianeptine against PTZ seizures was mitigated when tianeptine was administered with naloxone. Impairment of learning and memory by PTZ was prevented by tianeptine. Tianeptine also attenuated the seizure-induced increased oxidative stress. Thus, tianeptine showed an anticonvulsant effect along with amelioration of seizure-induced cognitive impairment and oxidative stress. Hence, tianeptine could be a useful drug in epileptic patients with depression, with the advantage of having both antidepressant and antiepileptic effects.

Anticonvulsant and neuroprotective effects of apelin-13 on pentylenetetrazole-induced seizures in male rats.

Epilepsy is a common neurological disorder with no effective treatment or cure. Neuropeptide apelin is an endogenous ligand of angiotensin receptor-like 1 (APJ). It has been shown that apelin has protective and anti-neurodegenerative properties. This study was designed to evaluate the effect of apelin-13 on pentylenetetrazole (PTZ)-induced rat model of seizure. Adult male Wistar rats were divided into the experimental groups as follows: control group receiving PTZ; apelin-treated group which received apelin-13 before PTZ; apelin+F13A-treated group which received apelin-13 plus the apelin receptor antagonist (F13A) before PTZ; apelin+naloxone group which received apelin-13+naloxone before PTZ. Behavioral scoring was used to access seizure. The expression level of APJ was measured by western blotting. Neuronal degeneration, apoptosis and astrocyte activation were evaluated by vanadium acid fuchsin (VAF) staining and immunohistochemistry. Our data demonstrated that apelin-13 pretreatment significantly inhibited seizure threshold (p<0.001) and tonic-clonic latency (p<0.001) compared with the control group. In addition, PTZ-induced up-regulation of APJ was attenuated by apelin-13 treatment. Histological and immunohistochemical findings also showed that apelin-13 could protect cortical neurons against PTZ-induced neuroinflammation and apoptosis. In conclusion, apelin-13 has anticonvulsive and neuroprotective properties against PTZ-induced seizure in rats and provided a new pharmacological aspect of the neuropeptide apelin.

DESIGN, FACILE SYNTHESIS, AND BIOLOGICAL EVALUATION OF NOVEL 1,3-THIAZINE DERIVATIVES AS POTENTIAL ANTICONVULSANT AGENTS

ABSTRACTObjective: Chalcones and their heterocyclic analogs represent an important class of small molecules having anticonvulsant activities. Therefore, inthis study, the synthesis and anticonvulsant activity of some new chalcones and 1,3-thiazines were described.Methods: The reaction of 1-acetylnaphthalene with substituted aromatic aldehydes in the presence of aq. NaOH afforded corresponding chalconeswhich upon further cyclization with thiourea resulted in 1,3-thiazine derivatives. The newly synthesized compounds were tested for anticonvulsantactivity by pentylenetetrazole-induced seizures method using diazepam as standard.Results: Most of the compounds showed good anticonvulsant activity but is less than diazepam. 1,3-thiazines were more potent than chalconesand among them, compound P4 containing 4-fluorophenyl substituents on the thiazine moiety was more potent as it has prolonged the onset ofconvulsions by 155.2 seconds.Conclusion: We described the synthesis and anticonvulsant activity of novel chalcones and 1,3-thiazine derivatives. 1,3-thiazines are more activeanticonvulsant agents than chalcones and in particular compounds with electron withdrawing substituents.Keywords: Chalcone, 1,3-thiazine, Pentylenetetrazole.

The cannabinoid CB2 receptor-specific agonist AM1241 increases pentylenetetrazole-induced seizure severity in Wistar rats

The potential efficacy of cannabinoid receptor ligands for the treatment of epilepsy remains controversial; cannabis components that act via cannabinoid type 1 (CB1) receptors produce anticonvulsant effects in animal models despite treatment with the CB receptor agonist reliably inducing convulsions in various species. Moreover, the potential role of cannabinoid receptor type 2 (CB2) to modulate seizures remains under-investigated. This study assessed the effects of the selective CB2 receptor agonist, AM1241, on pentylenetetrazole (PTZ)-induced seizures in rats. A stereotactically placed guide cannula was surgically implanted into the right lateral ventricle in adult Wistar rats which, 5–6days later, received an acute intracerebroventricular (i.c.v.) microinfusion of AM1241 (0.01, 1 or 10μg/2μl or vehicle) 5min before intraperitoneal (i.p.) injection of PTZ (70mg/kg). Rats were observed for 30min and the seizure severity behavior measured using a modified Racine's scale. Additional groups of rats were pretreated with a single low dose of the selective CB2 receptor antagonist, AM630 (dose 1mg/kg; i.p.), or vehicle, 30min prior to i.c.v. microinfusion of AM1241 (1μg/2μl). AM1241 administration significantly increased tonic-clonic seizure incidence and severity while also decreasing the onset of generalized seizures (AM1241 1 and 10μg/2μl). Pretreatment with AM630 prevented the proconvulsant effects of AM1241. This study shows, for the first time, that selective activation of CB2 receptors can increase generalized seizure susceptibility and suggests that pathological hyperexcitability phenomena can be differentially regulated by targeting CB1 and CB2 receptors.

Anticonvulsant effects of iridoid glycosides fraction purified from Feretia apodanthera Del. (Rubiaceae) in experimental mice models of generalized tonic-clonic seizures.

BackgroundDespite the increasing number and variety of antiepileptic drugs, nearly 30 % of epileptic patients who receive appropriate medical attention have persisting seizures. Anticonvulsant activity has been demonstrated for different iridoid glycoside-rich plant extracts. This study was designed to investigate the anticonvulsant effects of iridoid glycosides purified from Feretia apodanthera and to explore the possible mechanisms involved in antiepileptic activity.MethodsThe anticonvulsant effects of iridoid glycosides extracts were investigated against 2.7 mg/kg bicuculline- and 70 mg/kg pentylenetetrazole-induced convulsions. The behavioural and electroencephalographic manifestations of 50 mg/kg pentylenetetrazole-induced seizures in mice as a model of generalized tonic-clonic seizures were also evaluated. Finally, the extracts were tested on the course of kindling development, kindled-seizures and oxidative stress markers in 30 mg/kg pentylenetetrazole-kindled mice. Their effects on brain GABA content were also determined.ResultsThe iridoid glycosides (30–90 mg/kg) protected mice against bicuculline-induced motor seizures in all pre-treated animals. Behavioural seizures- and mortality-induced by 70 mg/kg pentylenetetrazole were strongly antagonized by the extracts (60–90 mg/kg). The number of crisis (n/20 min), the cumulative duration of crisis (sec/20 min), and the mean duration of crisis (sec) recorded in 50 mg/kg pentylenetetrazole-treated mice were significantly decreased in all pre-treated mice with the extracts (60–90 mg/kg). Administration of the extracts (30–90 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure mean stage and decreased the number of myoclonic jerks in 30 mg/kg pentylenetetrazole-kindled mice. Pentylenetetrazole kindling induced significant oxidative stress and brain GABA content alteration that was reversed by pretreatment with the extracts in a dose-dependent manner.ConclusionsThe results indicate that pretreatment with the iridoid glycosides extracts of Feretia apodenthera improves generalized tonic-clonic seizures-induced by chemo-convulsants, protects mice against kindling development and oxidative stress, and improves brain GABA content in pentylenetetrazole-kindled mice.

Pentylenetetrazol-induced seizures strength in diabetic and normal serum glucose elevated male mice

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Epilepsy is one of the most important neurological disorders, afflicting both genders during their lifetime. Metabolic disturbances, including hyperglycemia and hypoglycemia, are one of the main reasons of seizures in which frequently have been seen in diabetes mellitus. A large body of literature has investigated correlation between hyperglycemia, hypoglycemia and seizure. However, a definitive conclusion has not been taken, yet. Hence, we developed a rodent model of PTZ-induced seizure in order to investigate about relation between PTZ-induced seizures and glycemic changes, including diabetic and non-diabetic hyperglycemia and hypoglycemia.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We chose 50 naive, adult male inbred mice of the Balb/c strain (aged 8–10 weeks, weighted 25-35 grams) and divided them into 5 groups, randomly (n=10 in each groups): 1. Control (received saline and citrate buffer). 2. Diabetic group (received STZ 140 mg/kg I.P). 3. Diabetic+Glibenclamide group (received STZ 140 mg/kg I.P and treated with Glibenclamide 1 mg/kg I.P daily). 4. Non-diabetic hyperglycemic group (received glucose "D-dextrose" 2 g/kg I.P 30 min before PTZ administration. 5. Hypoglycemic group (the animals were fasted one day other days during experimental period). Chemical kindling was induced by PTZ injection (35 mg/kg, I.P), every other days (11 periods that lasted 22 days). &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Our data shown non-diabetic hyperglycemic mice that had elevated blood glucose levels, were more resistant to seizures compared to control group (p&amp;lt;0.05). Threshold and duration of the second phase of the seizures in non-diabetic hyperglycemic mice were increased (p&amp;lt;0.001). Moreover, threshold of the phase 5 was enhanced (p&amp;lt;0.001).&lt;strong&gt; &lt;/strong&gt;Again, hypoglycemic mice had statistically significant decrease in threshold of phase 5 compared to control group (p&amp;lt;0.05).&lt;/p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; We found that acute non-diabetic hyperglycemia not only have had no aggravating effects on seizure susceptibility but also have shown anticonvulsive effects. As well, we found that hypoglycemia has decreased threshold of phase 5 in challenge dose, i.e. onset of the most severe phase of the seizures was accelerated.

Interactive effects of prenatal exposure to restraint stress and alcohol on pentylenetetrazol-induced seizure behaviors in rat offspring.

Prenatal exposure to stress or alcohol increases vulnerability of brain regions involved in neurobehavioral development and programs susceptibility to seizure. To examine how prenatal alcohol interferes with stress-sensitive seizures, corticosterone (COS) blood levels and pentylenetetrazol (PTZ)-induced seizure behaviors were investigated in rat pups, prenatally exposed to stress, alcohol, or both. Pregnant rats were exposed to stress and saline/alcohol on 17, 18, and 19 days of pregnancy and divided into four groups of control-saline (CS), control-alcohol (CA), restraint stress-saline (RS), and restraint stress-alcohol (RA). In CS/CA groups, rats received saline/alcohol (20%, 2g/kg, intraperitoneally [i.p.]). In RS/RA groups, rats were exposed to restraint stress by being held immobile in a Plexiglas® tube (twice/day, 1h/session), and received saline/alcohol, simultaneously. After parturition, on postnatal days 6 and 15 (P6 & P15), blood samples were collected from the pups to determine COS level. On P15 and P25, PTZ (45mg/kg) was injected into the rest of the pups and seizure behaviors were then recorded. COS levels increased in pups of the RS group but not in pups of the RA group. Both focal and tonic-clonic seizures were prevalent and severe in pups of the RS group, whereas only focal seizures were prominent in pups of the CA group. However, pups prenatally exposed to co-administration of alcohol and stress, unexpectedly, did not show additive epileptic effects. The failure of pups prenatally exposed to alcohol to show progressive or facilitatory epileptic responses to stressors, indicates decreased plasticity and adaptability, which may negatively affect HPA-axis performance or hippocampal structure/function.

Inhibitor effect of paricalcitol in rat model of pentylenetetrazol-induced seizures.

Vitamin D has various systemic effects on bone metabolism, modulation of the immune system, stabilization of the cell membrane, oxidative stress, inflammation, apoptosis, and various other hormones. Differing from active vitamin D, paricalcitol is a relatively safe VDR agonist due to its relatively few side effects. This study has investigated the anticonvulsant effect of paricalcitol in convulsions induced by pentylenetetrazole (PTZ). 36 male Sprague-Dawley rats were divided randomly into two groups: 18 for EEG recording (PTZ 35mg/kg) and 18 for behavioral studies (PTZ 70mg/kg). Forty-five minutes before the PTZ injection, both groups of rats were given 5 and 10μg/kg of paricalcitol i.p., respectively. Racine convulsion scores, first myoclonic jerk time, spike percentages, and antioxidant status were evaluated in the groups. Our results showed that the Racine's Convulsion Scale (RCS) score significantly dropped in the paricalcitol-treated group, analysis of the first myoclonic jerk (FMJ) latencies demonstrated a significantly longer latency in the paricalcitol-applied group, and spike percentages at EEG recordings significantly decreased with paricalcitol. Moreover, MDA levels were lower and SOD activity were higher in the 5μg/kg paricalcitol group compared to the saline group; these results were more prominent in 10μg/kg paricalcitol group. Our study has demonstrated that paricalcitol has protective effects on PTZ-induced convulsions. Based on the SOD and MDA levels in our study, these effects may result from the antioxidant characteristics of paricalcitol.

Anticonvulsant Activity of Hydroalcoholic Extract ofCitrullus colocynthisFruit

This study investigated the anticonvulsant activity of Citrullus colocynthis fruit extract used traditionally in the treatment of convulsion. Albino mice were pretreated with extract in different doses (10, 25, 50, and 100 mg/kg), prior to injection of pentylenetetrazole. Animals received pretreatments with naloxone and flumazenil to further clarify the mechanisms of anticonvulsant action. The total flavonoid content of Citrullus colocynthis extract was also determined. Citrullus colocynthis hydroalcoholic extract with doses 25 and 50 mg/kg prolonged the onset of seizures and decreased the duration compared with control group. Pretreatment by flumazenil could inhibit the effect of Citrullus colocynthis on latency of seizure to some extent and administration of naloxone significantly inhibited changes in latency and duration of seizure produced by Citrullus colocynthis This study showed that Citrullus colocynthis has significant anticonvulsant effect in pentylenetetrazole-induced seizures in mice, and these effects may be related to its effect on γ-aminobutyric acid-ergic and opioid systems. These results confirmed the traditional use of Citrullus colocynthis in Iranian traditional medicine.

Experimental study of new pyrazolo[3,4-D]pyrimidine-4-one derivatives for anticonvulsant activity spectrum

Aim. To determine an effective dose range of three compounds of pyrazolo[3,4-d]pyrimidin-4-one derivatives in a basic pentylenetetrazole-induced seizure model and spectrum of anticonvulsant activity in experimental models of seizure with different pathogenetic mechanisms.Materials and methods. The experiments were performed on 240 mature albino male mice weighing 19–29 g. The dose dependence was investigated on a basic screening model of pentylenetetrazole-induced seizures on mice. Mice were exposed to electrical stimuli lasting for 0.2 s (50 Hz, 50mA) using corneal electrodes in another conventional maximal electroshock seizure model. A neurotransmitter profile of the leading compound effect was determined in picrotoxin-, thiosemicarbazide, strychnine- and caffeine-induced seizure models. Compounds and reference-drug were administered intragastrically 30 min before a subcutaneous (for picrotoxin and strychnine) or an intraperitoneal (for caffeine and thiosemicarbazide) convulsant administration.Results. Compound 78553 (200 mg/kg) and compound 78342 (100 mg/kg) have demonstrated the most marked anticonvulsant properties in the pentylenetetrazole-induced seizure model which effects are comparable to those of valproate sodium (300 mg/kg). Only compound 78553 (1-(4-metoxyphenyl)-5-{2-[4-(4-metoxy-phenyl)piperazine-1-yl]-2-oxoethyl}-1,5-dihydro-4H-pyrazole[3,4-d]pyrydine-4-one) had a moderate anticonvulsant effect in maximal electroshock seizure test. In seizure models with different pathogenetic mechanisms the compound 78553 has demonstrated an obvious effect on caffeine-induced seizures, moderate effect on picrotoxin-induced seizures (at relatively low dose of anticonvulsant), and insignificant effect on strychnine-induced seizures.Conclusions. The spectrum of anticonvulsant activity results of the leading compound 78553 in the seizure models with different pathogenesis has shown its potential mechanisms to include a stimulated effect on GABAergic processes (antagonism to pentilenetetrazole), as well as antagonism to blocking GABA-activated chloride channels (moderate antagonism to picrotoxin), on the adenosinergic link (marked antagonism to caffeine) and on the neural membrane permeability to sodium (moderate reduction of a maximum electroconvulsive seizure). Glycinergic action (moderate antagonism to strychnine convulsive effect) may play a minor role. The study compound has produced no effect on thiosemicarbazide-induced seizures

Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons.