Minimal Clonic Seizures Research Articles

The effects of ethanolic extract of Punica granatum Peel on Pentylenetetrazole-induced seizures in mice

Introduction: Pomegranate (Punica granatum L) is an ancient and unique fruit used as antioxidant, antidiabetic, anti-obesity, and antihypertensive. Considering oxidative stress and its relationship with convulsions and the antioxidant properties of pomegranate extract, the present study aimed to investigate the effect of ethanolic extract of Punica granatum peel on pentylenetetrazole (PTZ)-induced seizures in mice. Method: In this experimental study, male rats were randomly divided into four groups (n=8 in each group, PTZ group, and three groups received 100, 200, and 400 mg/kg of the extract). Thirty minutes after peritoneal injection of different doses of the extract, PTZ (100 mg/kg) was injected, and the mice were immediately transferred to a special cage, and the seizure parameters were evaluated for 60 minutes. Results: The results implicated that treating with ethanolic extract of Punica granatum peel in different doses of 100, 200, and 400 mg/kg body weight could delay the onset of minimal clonic seizures (MCS) caused by PTZ injection. In addition, doses of 200 and 400 mg/kg delay the onset of generalized tonic-clonic seizures (GTCS) caused by PTZ injection (P<0.001 to P<0.05). The anti-seizure effects of the ethanolic extract of Punica granatum were dose-dependent; therefore, the high doses have the most prophylactic effects against MCS and GTCS seizures (P<0.05). Conclusion: The results of this study showed that treatment with ethanolic extract of Punica granatum peel has an anti-seizure effect on mice, and the highest anti-seizure effect was observed in the highest dosage

Nicorandil Exerts Anticonvulsant Effects in Pentylenetetrazol-Induced Seizures and Maximal-Electroshock-Induced Seizures by Downregulating Excitability in Hippocampal Pyramidal Neurons.

N-(2-hydroxyethyl) nicotinamide nitrate (nicorandil), a nitrate that activates adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, is generally used in the treatment of angina and offers long-term cardioprotective effects. It has been reported that several KATP channel openers can effectively alleviate the symptoms of seizure. The purpose of this study was to investigate the improvement in seizures induced by nicorandil. In this study, seizure tests were used to evaluate the effect of different doses of nicorandil by analysing seizure incidence, including minimal clonic seizure and generalised tonic-clonic seizure. We used a maximal electroshock seizure (MES) model, a metrazol maximal seizure (MMS) model and a chronic pentylenetetrazol (PTZ)-induced seizure model to evaluate the effect of nicorandil in improving seizures. Each mouse in the MES model was given an electric shock, while those in the nicorandil group received 0.5, 1, 2, 3 and 6mg/kg of nicorandil by intraperitoneal injection, respectively. In the MMS model, the mice in the PTZ group and the nicorandil group were injected subcutaneously with PTZ (90mg/kg), and the mice in the nicorandil group were injected intraperitoneally with 1, 3 and 5mg/kg nicorandil, respectively. In the chronic PTZ-induced seizure model, the mice in the PTZ group and the nicorandil group were injected intraperitoneally with PTZ (40mg/kg), and the mice in the nicorandil group were each given 1 and 3mg/kg of PTZ at a volume of 200nL. Brain slices containing the hippocampus were prepared, and cell-attached recording was used to record the spontaneous firing of pyramidal neurons in the hippocampal CA1 region. Nicorandil (i.p.) significantly increased both the maximum electroconvulsive protection rate in the MES model and the seizure latency in the MMS model. Nicorandil infused directly onto the hippocampal CA1 region via an implanted cannula relieved symptoms in chronic PTZ-induced seizures. The excitability of pyramidal neurons in the hippocampal CA1 region of the mice was significantly increased after both the acute and chronic administration of PTZ. To a certain extent, nicorandil reversed the increase in both firing frequency and proportion of burst spikes caused by PTZ (P < 0.05). Our results suggest that nicorandil functions by downregulating the excitability of pyramidal neurons in the hippocampal CA1 region of mice and is a potential candidate for the treatment of seizures.

Neuroprotective effects of the fractions of Ocimum basilicum in seizures induced by pentylenetetrazole in mice.

Neuroprotective and antioxidant effects of Ocimum basilicum (O. basilicum) against pentylenetetrazole (PTZ)-induced seizures were investigated. Mice were divided as follows: (Group 1) Control, (Group 2) PTZ, (Groups 3-5) 50,100 and 200 mg/kg hydro-ethanolic (HE) extract, and (Groups 6-8) 200 mg/kg ethyl-acetate (EAF), N-hexane (NHF) and water (WF) fractions. Minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) latencies were measured. Biochemical and histological studies were done. MCS and GTCS latency in HE groups were longer than the PTZ group (p<0.05 to p<0.001). EAF and NHF prolonged the onset of MCS and GTCS (p<0.001). PTZ increased malondialdehyde (MDA) and dark neuron (DN) production while decreased thiol, catalase (CAT) and superoxide dismutase (SOD) (p<0.05 to p<0.001). Pre-treatment by HE and all fractions of the plant attenuated MDA and DN while increased thiol, CAT and SOD (p<0.01 to p<0.001). EAF and NHF had anticonvulsant properties. The extract and fractions protected the brain from PTZ-induced oxidative damages and showed neuroprotective effects.

Effect of hydro-alcoholic extract of Cinnamomum zeylanicum on nitric oxide metabolites in brain tissues following seizures induced by pentylenetetrazole in mice.

Objective:The effects of Cinnamomum zeylanicum on oxidative stress imposed by pentylenetetrazole (PTZ) was examined in mice brain tissues. Materials and Methods:Animals were divided into five groups as follows: 1- control group which received saline; 2- PTZ group (100 mg/kg, ip); and groups 3 to 5 which received (100, 200, and 400 mg/kg) of C. zeylanicum for seven days prior to PTZ injection. The latencies of the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizure (GTCS) and levels of oxidant and antioxidant biomarkers were measured.Results:Treatment with the two higher doses of the extract significantly increased the MCS and GTCS latencies (p<0.05 to p<0.001). Malondialdehyde (MDA) and nitric oxide (NO) levels were increased, but superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in both cortical and hippocampal tissues of the PTZ group compared to the controls (p<0.001). Pretreatment with the two higher doses of C. zeylanicum significantly led to a significant correction in NO, MDA, SOD and CAT levels in the hippocampus and cortex compared to the PTZ group (p<0.05 to p<0.001). Conclusion:Antioxidant and anticonvulsant effects of C. zeylanicum in PTZ-injected animals may suggest its potential therapeutic effect on nervous diseases such as seizures.

Improving Effect of Ethyl Acetate Fraction of Tanacetum Parthenium Against Brain Oxidative Damage in Pentylenetetrazole-Induced Seizure Model in Mice

Aims Oxidative stress plays an essential role in the pathogenesis of seizures. In this study, we investigated the effect of ethyl acetate fraction of Tanacetum parthenium against oxidative brain damage in a pentylenetetrazole(PTZ)-induced seizure model in mice. Methods &amp; Materials In this experimental study, mice were divided into 6 groups: control, PTZ, and 4 other groups that, besides PTZ, received 25, 50, 100, and 200 mg/kg of the fraction. PTZ (100 mg/kg) and a fraction (30 min before PTZ) were administered intraperitoneally for 3 weeks. Delay in the onset of the minimal clonic seizure (MCS), generalized tonic-clonic seizure (GTCS), and the level of oxidative stress indexes in cortical and hippocampal tissues were measured. Findings Pretreatment with fraction resulted in postponing the onset seizures in the Fraction+PTZ groups compared to the PTZ group (P&lt;0.05, P&lt;0.01, and P&lt;0.001). In addition, all doses of ethyl acetate fraction decreased the concentration of malondialdehyde (MDA) and increased the level of tom thiol groups and the activity of superoxide dismutase and catalase enzymes in the brain tissues compared to the PTZ group. Conclusion Ethyl acetate fraction of Tanacetum parthenium attenuated PTZ-stimulated seizures through improving brain tissue oxidative stress.

Anticonvulsant Action of GluN2A-Preferring Antagonist PEAQX in Developing Rats.

The GluN2A subunit of N-methyl-D-aspartate (NMDA) receptors becomes dominant during postnatal development, overgrowing the originally dominant GluN2B subunit. The aim of our study was to show changes of anticonvulsant action of the GluN2A subunit-preferring antagonist during postnatal development of rats. Possible anticonvulsant action of GluN2A-preferring antagonist of NMDA receptors P = [[[(1S)-1-(4-bromophenyl)ethyl]amino](1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl]phosphonic acid tetrasodium salt (PEAQX) (5, 10, 20 mg/kg s.c.) was tested in 12-, 18-, and 25-day-old rats in three models of convulsive seizures. Pentylenetetrazol-induced generalized seizures with a loss of righting reflexes generated in the brainstem were suppressed in all three age groups in a dose-dependent manner. Minimal clonic seizures with preserved righting ability exhibited only moderately prolonged latency after the highest dose of PEAQX. Anticonvulsant action of all three doses of PEAQX against cortical epileptic afterdischarges (generated in the forebrain) was found in the 25-day-old animals. The highest dose (20 mg/kg) was efficient also in the two younger groups, which might be due to lower specificity of PEAQX and its partial affinity to the GluN2B subunit. Our results are in agreement with the postero-anterior maturation gradient of subunit composition of NMDA receptors (i.e., an increase of GluN2A representation). In spite of the lower selectivity of PEAQX, our data demonstrate, for the first time, developmental differences in comparison with an antagonist of NMDA receptors with a dominant GluN2B subunit.

Neuroprotective effects of Pinus eldarica in a mouse model of pentylenetetrazole-induced seizures.

Objective:Oxidative stress has pernicious effects on the brain. Pinus eldarica has antioxidant properties. We explored neuroprotective effect of P. eldarica against pentylenetetrazole (PTZ)-induced seizures.Materials and Methods:Male mice (BALB/c) were grouped as control, PTZ, Soxhlet (Sox) 100, Sox 200, Macerated (Mac) 100 and Mac 200 groups. Sox and Mac extracts (100 and 200 mg/kg) were injected during 7 days. Delay in onset of minimal clonic seizure (MCS) and generalized tonic- clonic seizure (GTCS) was measured. Number of dark neurons (DN) and levels of oxidative stress indicators in the hippocampus were evaluated. Results:Onset of MCS and GTCS was later in groups treated with the extracts than the PTZ group (p<0.01 and p<0.001). Number of DN in the hippocampus in the PTZ group was higher than the control group (p<0.001) while in the extract groups, was lower than the PTZ group (p<0.05, p<0.01 and p<0.001). MDA level was higher whereas total thiol level and activity of SOD and CAT were lower (p<0.001) in the PTZ group than the control group. MDA level in the Sox 100 (p<0.01), Sox 200 (p<0.001) and Mac 200 (p<0.01) groups was less than the PTZ group. Total thiol level in the Sox 200 (p<0.001), SOD in the Sox 100 (p<0.05), Sox 200, and Mac 200 and CAT in the Sox 200 (p<0.001) groups were higher than the PTZ group. Conclusion: P. eldarica prevented neuronal death and reduced seizures caused by PTZ via improving brain oxidative stress.

Perampanel exhibits anticonvulsant action against pentylentetrazol-induced seizures in immature rats

Perampanel is a new antiepileptic drug with unique mechanism of action – antagonism of AMPA receptors. Its action in immature animals is not yet sufficiently known therefore we started to study anticonvulsant action of perampanel pretreatment (1–20 mg/kg i.p.) against seizures elicited by pentylenetetrazol. Three age groups of rats were examined – 12, 18 and 25 days old. Perampanel selectively suppressed the tonic phase of generalized seizures in the two younger groups and whole tonic-clonic seizures in the 25-day-old group. It exhibited also an anticonvulsant action against minimal clonic seizures present in control 18- and 25-day-old rats.Perampanel is an effective anticonvulsant drug even at very early stages of brain development.

Effects of Hydro-ethanolic Extract of Tanacetum parthenium and its N-Butanol and Aqueous Fractions on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice

Background: Epileptic seizures affect the life of noticeable number of people in all over the world. Tanacetum parthenium (TP) is used in traditional medicine. We studied the effects of hydro- ethanolic extract of TP and its n-butanol and aqueous fractions on brain oxidative damage in pentylenetetrazole (PTZ)-induced seizures in mice. Methods: Male mice were divided into: (1) Control; (2) PTZ (100 mg/kg, i.p.); (3-5) hydro-ethanolic extract of TP (50, 100 and 200 mg/kg); (6) n-butanol (NBut) (100 mg/kg) and (7) aqueous (Aq) (100 mg/kg) fractions. Extracts were injected (i.p.) for 3 days and 30 min before PTZ. Latencies in onset of Minimal Clonic Seizures (MCS) and Generalized Tonic-Clonic Seizures (GTCS) as well as biochemical indicators were evaluated. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Results: demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion: Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Suvorexant, a Dual Orexin Receptor Antagonist, Protected Seizure through Interaction with GABAA and Glutamate Receptors.

Orexin can increase neuronal excitability and induce epileptic activity. In this study, the effects of suvorexant (orexin receptor antagonist) on pentylenetetrazol (PTZ) and maximal electroshock (MES)-induced seizure were investigated. Mice were divided into 5 groups of six animals each including normal saline (10 mL/kg), diazepam (2 mg/kg), and suvorexant (50, 100 and 200 mg/kg) groups. In PTZ test, the latency to first minimal clonic seizure (MCS), latency to the first generalized tonic–clonic seizures (GTCS), total duration of seizure and also protection against mortality were evaluated. In MES, the hind limb tonic extension (HLTE) and the protection against mortality were recorded. In order to evaluate the role of GABAA in anticonvulsant effect of suvorexant, flumazenil was used and to investigate the role of glutamate, the protein levels of AMPAR and NMDAR were measured in hippocampus by western blotting. In PTZ model, suvorexant (200mg/kg) increased MCS and GTCS latencies. Suvorexant (100 and 200 mg/kg) decreased total duration of seizure compared to control group. In PTZ model, flumazenil inhibited the prolongation of seizure latency induced by suvorexant. In MES, the HLTE was decreased by suvorexant (100 and 200 mg/kg) and suvorexant was protected against mortality by 83.3%. Moreover, the protein levels of NMDAR and AMPAR were decreased by suvorexant. Suvorexant exerted anticonvulsant activity and in addition to its inhibitory effect on orexin receptors, this effect may be mediated, at least partly, through interaction with GABAA and glutamate receptors.

Interaction of GABAA and GABAB antagonists after status epilepticus in immature rats

Among neurotransmitter systems affected by status epilepticus (SE) in adult rats are both GABAergic systems. To analyze possible changes of GABAA and GABAB systems in developing rats lithium-pilocarpine SE was induced at postnatal day 12 (P12). Seizures were elicited by a GABAA antagonist pentylenetetrazol (PTZ) 3, 6, 9, and 13 days after SE (i.e., in P15, P18, P21, and P25 rats), and their possible potentiation by a GABAB receptor antagonist CGP46381 was studied. Pilocarpine was replaced by saline in control animals (lithium-paraldehyde [LiPAR]).Pentylenetetrazol in a dose of 50 mg/kg s.c. elicited generalized seizures in nearly all 15-day-old naive rats and in 40% of 18-day-old ones but not in older animals. After SE, PTZ no longer elicited seizures in these two younger groups, i.e., sensitivity of GABAA system was diminished. The GABAB antagonist exhibited proconvulsant effect in P15 and P18 SE as well as LiPAR rats returning the incidence of PTZ-induced seizures to values of control animals. A decrease in the incidence of minimal clonic seizures was seen in P21 LiPAR animals; these seizures in the oldest group were not affected. Change of the effect from proconvulsant to anticonvulsant (or at least to no action) took place before postnatal day 21.Both SE and LiPAR animals exhibited similar changes but their intensity differed, effects in LiPAR controls were usually more expressed than in SE rats.

Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice&lt;br /&gt;

Background: Frequent seizure is followed by overproduction of free radicals and brain oxidative stress. Renin angiotensin system (RAS) has some effects on central nervous system. We designed this research to challenge the effect of captopril as an angiotensin converting enzyme (ACE) inhibitor against brain oxidative stress in pentylenetetrazole (PTZ) -induced seizures in mice. Methods: The groups were including (1) Control (saline); (2) PTZ (100 mg/kg, i.p.), (3-5) PTZ- captopril (Capto) that received three doses of Capto 10, 50 and 100 mg/kg 30 min before PTZ injection. Latency time in the onset minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) were recorded. The level of malondialdehyde (MDA) and total thiol, as well as superoxide dismutase (SOD) and catalase (CAT) activity in the hippocampus and cortex were measured. Results: All doses of captopril postponed the onset of MCS and GTCS. Accumulation of MDA in the brain tissues of PTZ group was higher than control group, while total thiol content and CAT activity were lower. Pretreatment with captopril (100 mg/kg) diminished MDA concentration compared with PTZ group. Captopril (50 and 100 mg/kg) also increased the level of total thiol groups versus PTZ group. Captopril injection (50 and 100 mg/kg) elevated the activity of SOD and CAT in the brain tissues. In addition captopril administration diminished mortality rate caused by PTZ. Conclusion: Findings demonstrated that convulsions caused by PTZ were followed by oxidative stress status in the brain tissues. Pretreatment with captopril attenuated the effect of PTZ on brain tissue oxidative damage.&lt;br /&gt;

Edaravone acts as a potential therapeutic drug against pentylenetetrazole-induced epilepsy in male albino rats by downregulating cyclooxygenase-II.

IntroductionThe effects of edaravone against pentylenetetrazole (PTZ)‐induced epilepsy in male albino rats were investigated. Edaravone is a well‐known commercial drug used in the treatment of strokes and amyotrophic lateral sclerosis (ALS). Antioxidant and free radical scavenging activities of edaravone have been reported in patients with ALS.MethodsIn this study, the experimental groups were as follows: sham, control, 5 mg/kg edaravone, and 10 mg/kg edaravone. Behavioral assessment, determination of biochemical markers, apoptosis, nitric oxide (NO), and mRNA and protein expression of cyclooxygenase‐II (COX‐II) were carried out. Seizure incidence, including generalized tonic–clonic seizure (GTCS) and minimal clonic seizure (MCS), was directly associated with PTZ administration in rats.ResultsEdaravone supplementation substantially increased MCS and GTCS latency in rats, and biochemical markers were significantly altered in the brain tissue of PTZ‐treated rats. Edaravone treatment normalized altered biochemical markers compared with the untreated control. Apoptosis and NO levels were significantly reduced by more than 50% compared to their respective controls. COX‐II mRNA was increased by 130% in PTZ‐treated rats, while edaravone supplementation reduced mRNA and protein expression of COX‐II by more than 20% and 40%, respectively. Immunohistochemistry indicated that COX‐II protein expression was reduced by 13.2% and 33.7% following supplementation with 5 and 10 mg/kg edaravone, respectively.ConclusionTaken together, our results suggest that edaravone functions by downregulating the levels of COX‐II and NO and is a potential candidate for the treatment of PTZ‐induced epilepsy.

L-Homocarnosine, l-carnosine, and anserine attenuate brain oxidative damage in a pentylenetetrazole-induced epilepsy model of ovariectomized rats.

In this study, we investigated the protective effect of l-homocarnosine, l-carnosine, and anserine (HCA) on seizure-induced brain injuries. We evaluated the protective effect of HCA on brain oxidative damage in a pentylenetetrazole (PTZ)-induced epilepsy model using ovariectomized (OVX) rats. The experimental groups were as follows: group I, sham; group II, sham + PTZ; group III, sham + HCA + PTZ; group IV, OVX; group V, OVZ + PTZ; and group VI, OVX + HCA + PTZ. We determined the levels of lipid peroxidation, glutathione peroxidase (Gpx), reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and thiol in brain hippocampal and cortical tissue. The biochemical markers were significantly altered in the brain tissue of OVX rats. HCA supplementation significantly reduced lipid peroxidation and increased GSH, Gpx, SOD, catalase, and thiol levels in PTZ-treated OVX rats. Rats with an ovariectomy showed a significant protective effect against PTZ through elevation of the latency of generalized tonic-clonic seizures (GTCS). HCA substantially increased minimal clonic seizure and GTCS latency in the OVX-PTZ and sham-PTZ groups. In summary, our experimental data indicate that combined supplementation of HCA substantially increased anticonvulsant activity. Moreover, combined HCA supplementation reduced oxidative damage by decreasing lipid peroxidation and increasing antioxidant levels in the brain of a PTZ-induced seizure rodent model.

The Effects of Aqueous Extract of Apium Graveolens on Brain Tissues Oxidative Damage in Pentylenetetrazole-induced Seizures Model in Rat

Introduction: An important role for oxidative stress both as a consequence and as a cause of epileptic seizures has been suggested. Regarding the antioxidant and central nervous system depressant effects of Apium graveolens, the effects of aqueous extract of the plant on the brain tissues oxidative damage in pentylenetetrazole (PTZ)-induced seizures model was investigated. Materials & methods: Male Wistar rats were divided into 5 groups and treated: Control (saline), PTZ and three doses of the Apium graveolens extract (100, 500 and 1000 mg/kg) before PTZ. Latency to the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) were recorded. The brain tissues were then removed for biochemical measurements. Results: MCS and GTCS latencies in extract treated groups were significantly higher than that of PTZ group (P < 0.05-P< 0.01). The malondialdehyde (MDA) levels in the brain tissues of PTZ group were significantly higher than that of control animals (P < 0.01-P< 0.001). Pretreatment with the extract resulted in a significant reduction in the MDA levels (P < 0.05-P< 0.001). Following PTZ administration, a significant reduction in total thiol content was observed in the brain tissues (P < 0.05- P < 0.01). Pretreatment with the extract was not effective to prevent from the lowering effects of PTZ- induced seizures on total thiol concentrations in the brain tissues. Conclusion: The present study showed that aqueous extract of Apium graveolens aerial parts possess anticonvulsant activity. This activity is accompanied by an antioxidant effect in the brain.

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&lt;0.001) concentration while, diminished thiol contents (P&lt;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&lt;0.001). Both 50 and 200 mg/kg of the extract improved thiol concentration in the hippocampal tissues (p&lt;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.

Anticonvulsant effect of Satureja hortensis aerial parts extracts in mice.

Regarding the anticonvulsant effects of Satureja hortensis (S . hortensis) in Avicenna's book: canon of medicine; the present study was undertaken to evaluate the anti- eplileptic effects of S . hortensis aqueous and ethanolic aerial part extracts. Furthermore, the mechanisms of their anticonvulsant activities were also evaluated. Seizure was induced by Pentylentetrazol (PTZ) and MES (maximal electroshock) models. Mice were randomly divided into 8 groups; negative control (normal saline, 10ml/Kg), positive control (diazepam, 2 mg/kg), S. hortensis aqueous and ethanolic extracts (200, 400 and 600 mg/kg). In PTZ test, latency to the first minimal clonic seizure (MCS), latency to the first generalized tonic-clonic seizures (GTCS), the total duration of seizures and protection against mortality were evaluated. In MES test, the stretching length of extremities and protection against mortality were recorded. Aqueous and ethanolic extracts (400 and 600 mg/kg) significantly increased MCS and GTCS latencies in PTZ model. Three doses of the extracts decreased the total duration of seizure. These extracts did not show any protective effects on seizure induced by MES model. In PTZ model, flumazenil, an antagonist of benzodiazepine (BZD) site in the GABAA-BZD receptor complex and 7- nitroindazole (7- NI), a selective nNOS (neuronal nitric oxide synthase) inhibitor, reduced the prolongation of seizure latency. S. hortensis showed anticonvulsant activity in PTZ model and this effect may be mediated, at least partly, through interacting with nitric oxide and GABAA-BZD receptor complex.

The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats.

In the present work, the effects of different fractions of Coriandrum sativum (C. sativum), on pentylenetetrazole (PTZ)-induced seizures and brain tissues oxidative damage were investigated in rats. The rats were divided into the following groups: (1) vehicle, (2) PTZ (90 mg/kg), (3) water fraction (WF) of C. sativum (25 and 100 mg/kg), (4) n-butanol fraction (NBF) of C. sativum (25 and 100 mg/kg), and (5) ethyl acetate fraction (EAF) of C. sativum (25 and 100 mg/kg). The first generalized tonic-clonic seizures (GTCS) latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p<0.01). In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS) latency. Malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p<0.001). Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (p<0.01 - p<0.001). Following PTZ administration, a significant reduction in total thiol groups was observed in the brain tissues (p<0.05). Pretreatment with WF and NBF significantly elevated thiol concentrations in cortical and hippocampal tissues, respectively (p<0.05). The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects.

Effects of melatonin and theanine administration on pentylenetetrazole-induced seizures and brain tissue oxidative damage in ovariectomized rats.

The effects of coadministration of melatonin and theanine (Mel/Thea) on pentylenetetrazole (PTZ)-induced seizures and brain tissue oxidative damage were investigated in ovariectomized (OVX) and sham-operated rats. The rats were divided into the following groups: 1) sham, 2) ovariectomized (OVX), 3) sham-PTZ, 4) OVX- PTZ, 5) sham-Mel/Thea-PTZ, and 6) OVX-Mel/Thea-PTZ. Groups 1-4 received saline, while groups 5 and 6 received a combination of Mel/Thea for 6 weeks. All animals except for those in groups 1 and 2 received a single injection of PTZ. The OVX-PTZ group had higher generalized tonic-clonic seizure (GTCS) latency compared to the sham-PTZ group. Administration of Mel/Thea increased minimal clonic seizure and GTCS latencies in both the sham-Mel/Thea-PTZ and OVX-Mel/Thea-PTZ groups compared to the controls. Additionally, PTZ exposure increased malondialdehyde levels and reduced thiol concentrations in brain tissues of both the sham-PTZ and OVX-PTZ groups. Mel/Thea pretreatment resulted in MDA reduction and thiol increase in brain tissues. The results of this study demonstrated the antioxidant and anticonvulsant activities of Mel/Thea despite the presence or absence of ovarian hormones.

Anticonvulsant and anxiolyic activities of ethyl acetate fraction of Cassia fistula Linn. pods in mice

Context: Cassia fistula L. (Leguminacea) is used by Indian and Tanzanian traditional healers for treating various ailments related to the central nervous system. Aims: The present study aimed to evaluate the anticonvulsant and anxiolytic activity of the ethyl acetate fraction obtained from a hydroalcoholic extraction of Cassia fistula pods (EAFCF) and thereby to provide scientific validation for its traditional use. Methods: Preliminary phytochemical analysis and estimation of the flavonoid content of the ethyl acetate fraction was performed. Anticonvulsant activity was assessed by the subcutaneous pentylenetetrazole test (s.c. PTZ test). Anxiolytic activity was assessed by elevated plus maze (EPM) and open field tests (OFT). The sedative and motor toxicity was evaluated by a phenobarbitone induced sleep test and rotarod behavior respectively. Results: Photochemical analysis revealed the presence of a high flavanoid content in the ethyl acetate fraction. Treatment of EAFCF (50 and 100 mg/kg) significantly increased the latency to the onset of minimal clonic seizure and generalized tonic clonic seizure and animals were completely protected from death due to PTZ administration. Administration of EAFCF at the dose of 100 mg/kg markedly increased the open arm entries and time spent in open arm in EPM. In OFT, EAFCF increased the number of central squares crossed and time spent in the central compartment. EAFCF in the doses used in this experiment did not produce sedation or motor toxicity. Conclusion: The results obtained herein clearly indicate the anticonvulsant and anxiolytic activity of EAFCF which may be due to the high flavonoid content. These findings give the scientific support for common use of this plant for treating epilepsy and anxiety.