Convulsion Model Research Articles

A Comprehensive Study of the Neuropharmacological Profile of Methanol Leaf Extract of Aloe vera and Identification of Associated Neuroprotective Compounds through Gas chromatography-mass spectrometry Analysis

The objective of this study is to determine the neuropharmacological activities of the methanol extract of Aloe vera leaf and identify the potential bioactive compounds present in the same responsible for the activities through Gas chromatography–mass spectrometry analysis. The study is done on Wistar albino rats and composed of 5 groups, methanol extract of Aloe vera leaf at 200, 400, 800 mg/kg, normal saline (control) and standard drugs Phenytoin and Diazepam. Antiepileptic activities are done using maximal electroshock and pentylenetetrazole induced convulsion models and anxiolytic sedative activities using the staircase test, actophotometer test and sleep prolongation test. The chemometric analysis is performed using Clarus 500 Perkin Gas Chromatograph coupled with a mass detector, Turbo mass gold–Perkin Elmer Turbomass 5.1 spectrometer with an Elite-1 (100 % dimethyl polysiloxane), 30 m×0.25 mm ID×0.25 μm of the capillary column. The results demonstrated anxiolytic potential at 200 and 400 mg/kg and sedative activity at 800 mg/kg comparable to Diazepam. The methanolic extract of Aloe vera leaf at 800 mg/kg displayed antiepileptic activity compared to Phenytoin. The Gas chromatography–mass spectrometry analysis confirmed the presence of phytol (23.76), alpha-tocopherol (4.67), maltol (3.69), humulene (6.58), caryophyllene (2.73), n-hexadecanoic acid (2.16), hexadecanoic acid methyl ester (3.70), squalene (3.51), 9,12,15-octadecatrienoic acid methyl ester (2.12), which are antioxidant and anti-inflammatory compounds. These plant derived bioactive compounds are demonstrated to have antianxiety, antiepileptic, sedative hypnotic and neuroprotective potential in neurodegenerative models and might serve as future prospective drug candidates in neurodegenerative disorders).

Beneficial effects of ambroxol hydrochloride on pentylenetetrazol-induced convulsion model in rats

Beneficial effects of ambroxol hydrochloride on pentylenetetrazol-induced convulsion model in rats

Anticonvulsant activity 2-((5-(3-(4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)-thio)-1-arylethanone

The aim of work is to study of the anticonvulsant activity of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones, the establishment of some laws between the structure of compounds and their activity.Materials and methods. The study of the anticonvulsant activity of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones was carried out according to the test of interaction with agents that excite the central nervous system. The experiments were performed on the intact white rats of the Vistar line, weight 160–190 g, five animals in each group. As convulsive models, corazole-induced convulsions were used, which was caused by subcutaneous administration of corazole at a dose of 100 mc/kg.Then the animals were placed in individual transparent flexiglaz cameras and watched them for one hour. Six indicators of convulsions were recorded: the latent period, the number of animals with generalized clonic or tonic-clonic convulsions in the group, the number of animals with tonic extension, mortality and life expectancy.Results. The resulting compounds exhibit high anticonvulsant activity. So, against the background of the introduction of 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(3-fluorophenylethanone), 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone) and 2-((5-(4-fluorophenyl)-4-methyl-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone), the latent period of the onset of convulsions under the influence of corazole increases by 57.1 %, 67.3 % and 28.6 %, respectively (P < 0.05 ), and the duration of convulsions is reduced by 33.4 %, 31.5 % and 38.9 %, respectively (P < 0.05), which indicates the neuroprotective and membrane stabilizing effect of the corresponding 2-((5-(3-4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones. Comparison preparations of midocalm and phenobarbital increase the latent period of the onset of convulsive reactions by 51.0 % and 34.7 % at (P < 0.05), and the duration of convulsions decreased by 20.4 % and 14.9 % at (P < 0.05) respectively.Conclusions. The anticonvulsant activity of some 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones was studied for the first time on a model of corazole convulsions. Three active compounds are 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(3-fluorophenylethanone), 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone) and 2-((5-(4-fluorophenyl)-4-methyl-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone). In some cases, regularities were revealed between the structure of molecules and their activity.

Effects of the Hyptis martiusii Benth. leaf essential oil and 1,8-cineole (eucalyptol) on the central nervous system of mice

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.

Design, synthesis, and anticonvulsant evaluation of 4-GABA-3-nitrocoumarines, 1-thiocoumarines, quinolone-2-ones, and their derivatives

The novel group of 4-GABA-3-nitrocoumarines, 1-thiocoumarines, quinolone-2-ones, and their derivatives was designed as potential anticonvulsants using GABA pharmacophore and corresponding heterocyclic moieties. A number of compounds of this group were synthesized and studied in the maximum electroshock seizure (MES) test and in the model of primary-generalized convulsions caused by subcutaneous pentylenetetrazole (scPTZ) in mice. The most active compound in the MES test was found to be 1a (N-(3-nitrocoumarin-4-yl)-4-aminobutyric acid) at a dose range of 60–80 mg/kg that increased the number of survived animals up to 60% in comparison with the control group, whose survival rate was 10%. Compounds 1d (N-(3,6-dinitrocoumarin-4-yl)-4-amino-butyric acid methyl ester) at doses of 10–40 mg/kg and 3a (N-(3-nitro-2-oxo-1,2-dihydroquinolin-4-yl)-4-amino-butyric acid methyl ester) at a dose of 12.5 mg/kg had the most pronounced anticonvulsant effect in scPTZ test.

Ameliorative Effects of Ellagic Acid on Maximal Electroshock and Pentylenetetrazole-Induced Seizures in Mice

Background: Epilepsy is a series of disorders in the central nervous system defined by disruption and abnormality in the electrical activity of the brain. The mechanisms of epilepsy occurrence are not fully determined and the current pharmacological therapeutics have low efficacy and are associated with adverse reactions due to narrow therapeutic indices. Ellagic acid has neuroprotective and antioxidant effects and increases the brain’s GABA levels. Objectives: This study was designed to evaluate the effects of ellagic acid on both maximal electroshock and pentylenetetrazole models of acute seizures in mice. Methods: Ellagic acid was administered at the doses of 25, 50, and 100 mg/kg in the two models of seizures. Results: The results showed that ellagic acid was effective at the lowest dose in the maximal electroshock-induced seizure in mice and the duration of hind limb tonic extension (HLTE) was significantly shorter in this group than in the untreated convulsive group. In the pentylenetetrazole convulsion model, ellagic acid significantly increased the latency to convulsion and Straub tail response. The latencies with ellagic acid were longer in groups treated with ellagic acid 25 mg/kg than with ellagic acid 50 and 100 mg/kg. Conclusions: In conclusion, it seems that ellagic acid has anticonvulsant effects in electroshock and pentylenetetrazole models of convulsion but its effects are attenuated or eliminated at higher doses.

Neuro-pharmacological evaluation of anticonvulsant and neuroprotective activity of Cocculus laurifolius leaves in wistar rats.

The aim of the study was to evaluate the anticonvulsant and neuroprotective activity of Cocculus laurifolius D.C leaves in albino wistar rats against strychnine induced convulsions. Initially the extract was investigated for acute oral toxicity testing in order to examine any signs of toxicity and mortality. For anticonvulsant activity, the ethanolic extract was evaluated at doses 200 and 400mg/kg, p.o. against strychnine induced convulsions model, at 1, 7, 15 and 30th day of treatment. Meanwhile, the neuroprotective effect of the extract was investigated via histopathological assessment. Cocculus laurifolius (200 and 400mg/kg, p.o.) exhibited anticonvulsant activity as indicated by significant delay in the onset of convulsions and time to death after strychnine induced convulsions. Similarly, significant reduction in the duration of convulsions and percentage of mortality was observed by ethanolic extract (200 and 400mg/kg p.o.) at 1, 7, 15 and 30th day of test sessions. Furthermore, Cocculus laurifolius leaves (200 and 400mg/kg p.o.) also exhibited neuroprotective effect with considerable preserved neuronal structures and significant decrease in neuronal apoptosis, in comparison with control. The results obtained from the present study indicate that ethanolic extract of Cocculus laurifolius leaves possess potential anticonvulsant and neuroprotective effect against strychnine induced convulsions. Therefore, it can be concluded that Cocculus laurifolius leaves may be a valuable in management of epilepsy, however further studies are required on large number of animals to confirm these findings.

Assessment of Morus alba (Mulberry) leaves extract for anti-convulsant property in rats

Background: The mulberry tree, a plant of the family Moraceae and the genus Morus, has been widely cultivated to feed silkworms. Various parts of Morus alba linn used as an Anti-inflammatory, hypoglycemic, cardioprotective, hepatoprotective, free radical scavenging activity and neuroprotective agent. The plant contains flavonoids, moranoline, albanol, morusin coumarine, and stilbene, which have. In this study, anticonvulsant property of Morus alba leaves extract (MAE) was evaluated by using MES and PTZ induced convulsion in rats.Methods: Effects of MAE were evaluated in experimental models of electro convulsions, maximal electro shock (MES) and chemoconvulsion induced by pentylenetetrazole (PTZ) in rats (n=6), which were treated intraperitonially with doses of 100, 200 and 400mg/kg.Results: The duration of tonic hind limb extension (seconds) with MAE in MES induced convulsions at dose of 100, 200, 400 mg/kg is 8.33±1.21, 6.83±1.16 &amp; 3.16±0.98 respectively. In the dose of 400 mg/kg of MAE showed highly significant results by reducing the duration of tonic hind limb extension in MES induced convulsions. And onset of jerky movements (seconds) with MAE in PTZ induced convulsions at dose of 100, 200, 400mg/kg is 157.83±8.99, 195.66±17.02 and 295.50±21.10 respectively. In the dose of 400mg/kg of MAE showed highly significant results by delaying the onset of convulsions.Conclusions: Results indicate that the MAE have anticonvulsant effects in MES induced convulsions and in PTZ induced convulsions.

Neuropharmacological Screening of Chiral and Non-chiral Phthalimide- Containing Compounds in Mice: in vivo and in silico Experiments.

Thalidomide, the first synthesized phthalimide, has demonstrated sedative- hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4-aminopyridine (4-AP; 10 mg/kg). The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. The chiral compounds exhibited a non-competitive NMDAR antagonist profile and the non-chiral molecules possessed selective sedative properties. The NMDAR exhibited stereoselectivity for S-TGLU while it is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1.

Effects of levetiracetam on astroglial release of kynurenine-pathway metabolites.

Several preclinical studies have demonstrated the unique profiles of levetiracetam (LEV), inhibits spontaneous absence epilepsy models but does not affect traditional convulsion models; however, the detailed pharmacological mechanisms of action of LEV remain to be clarified. We determined the interaction between LEV and IFNγ regarding astroglial release of anti-convulsive (kynurenic acid and xanthurenic acid), pro-convulsive (quinolinic acid) and anti-convulsive but pro-absence (cinnabarinic acid) kynurenine-pathway metabolites from rat cortical primary cultured astrocytes using ultra-HPLC equipped with MS. IFNγ increased basal astroglial release of cinnabarinic acid and quinolinic acid but decreased that of kynurenic acid and xanthurenic acid. IFNγ enhanced inositol 1,4,5-trisphosphate (IP3 ) receptor agonist (adenophostin A, AdA)-induced astroglial release of kynurenine-pathway metabolites, without affecting AMPA-induced release. LEV increased basal astroglial release of kynurenic acid and xanthurenic acid without affecting cinnabarinic acid or quinolinic acid. Chronic and acute LEV administration inhibited AMPA- and AdA-induced kynurenine-pathway metabolite release. Upon chronic administration, LEV enhanced stimulatory effects of IFNγ on kynurenic acid and xanthurenic acid, and reduced its stimulatory effects on cinnabarinic acid and quinolinic acid. Furthermore, LEV inhibited stimulatory effects of chronic IFNγ on AdA-induced release of kynurenine-pathway metabolites. This study demonstrated several mechanisms of LEV: (i) inhibition of AMPA- and AdA-induced astroglial release, (ii) inhibition of IFNγ-induced IP3 receptor activation and (iii) inhibition of release of cinnabarinic acid and quinolinic acid with activation of that of kynurenic acid induced by IFNγ. These combined actions of LEV may contribute to its unique profile.

Molecular docking, synthesis and anticonvulsant activity of some novel 3-(2-substituted)-4-oxothiazolidine-3-yl)-2-phenylquinazoline-4(3H)-ones

As the therapeutic potential of quinazolinone and thiazolidinone is well mentioned in literature for their versatile biological activities, their related toxicological profiles cannot be ignored. So, the purpose of this study is to synthesize 3-(2-substituted)-4-oxothiazolidine-3-yl)-2-phenylquinazoline-4(3H)-ones (3a–3k) and evaluate them as anticonvulsant agents. Novel series of 3a–3k were synthesized and their structures elucidated on the basis of elemental and spectral analyses. A hybrid scaffold containing quinazolinone and thiazolidinone moieties was synthesized to get the title compounds, and their in vivo anticonvulsant activities were performed by maximal electro-shock (MES) induced convulsion model at a dose of 25 mg/kg body weight. Six compounds, 3b, 3c, 3d, 3e, 3f and 3i, were found to have significant anticonvulsant activities with their durations of tonic hind limb extension ranging from 13.117 to 16.450 s and animal protection from 83 to 100%. The results were compared with the standard. All compounds exhibited good binding energies ranging from − 5.15 to − 6.13 kcal/mol with sodium channel IIA inactivation gate (PDB ID: 1BYY) in molecular docking study; amongst them, 3d has shown significant binding energy of − 6.13 kcal/mol. The obtained result showed that biologically active compounds could be used as a template for future design, optimization and investigation for producing more active analogs.

Влияние сочетанного применения цитиколина и антител к глутамату на развитие острых генерализованных судорог, вызванных пентилентетразолом у мышей

Цель исследования. На 2 моделях острых генерализованных судорог (ОГС), вызванных конвульсантом пентилентетразолом (ПТЗ), изучить эффективность сочетанного применения ноотропа цитиколина - препарата с противосудорожным действием, нейрорегенеративной, нейропротекторной активностью и антител (АТ) к глутамату, обладающих противосудорожной активностью. Методика. Эксперименты выполнены на мышах-самцах линии C57Bl/6 (n = 87) массой 22-28 г. Эффективность сочетанного применения цитиколина и АТ к глутамату изучали на двух моделях ОГС. Выполнено 2 серии экспериментов. В 1-й серии ОГС вызывали внутривенным введением 1% раствора ПТЗ со скоростью 0,01 мл/с. Для изучения эффективности сочетанного применения препаратов определяли минимальное противосудорожное действие цитиколина (Цераксон, «Nicomed Ferrer Internaсional, S.A.») и АТ к глутамату при их внутрибрюшинном введении. С этой целью цитиколин вводили в дозах 500 и 300 мг/кг за 1 ч до введения ПТЗ, АТ к глутамату - в дозах 5 и 2,5 мг/кг за 1 ч 30 мин до введения ПТЗ. АТ к глутамату получали путем гипериммунизации кроликов соответствующим конъюгированным антигеном. Во 2-й серии ОГС вызывали подкожным введением ПТЗ в дозе 85 мг/кг. Для изучения эффективности сочетанного действия изучаемых препаратов последние вводили в минимально действующих дозах, установленных в 1-й серии экспериментов. Контролем во всех сериях опытов служили животные, которым вводили в аналогичных условиях и в том же объеме физиологический раствор. Результаты. Показано, что сочетанное применение цитиколина и АТ к глутамату в минимально действующих дозах (300 и 2,5 мг/кг соответственно) при моделировании ОГС не вызывало повышения судорожной активности мозга и усиления противосудорожных свойств препаратов. Заключение. Cочетанное применение цитиколина и АТ к глутамату в минимально действующих дозах не вызывало повышения судорожной активности мозга, что свидетельствует о безопасности совместного применения препаратов. Проведенное исследование может служить также экспериментальным обоснованием возможности использования сочетанного применения данных препаратов при судорогах с целью замедления прогрессирования нейродегенеративных процессов и благоприятного влияния на когнитивные функции. Aim. To study the effectivity of a combination of citicoline, a nootropic substance with neuroregenerative, neuroprotective, and anticonvulsant actions, and glutamate antibodies (АB) with an anticonvulsant action in two models of acute generalized convulsions (AGC) caused by the convulsant pentylenetetrazole (PTZ). Methods. Experiments were conducted on C57Bl/6 mice (n = 87) weighing 22-28 g. Effects of combined citicoline and glutamate АB were studied on two models of AGС. In the first series of experiments, AGС was induced by intravenous infusion of a 1% PTZ solution at 0.01 ml/sec. In the second series, AGС was induced by a subcutaneous injection of PTZ 85 mg/kg. To evaluate efficacy of the drug combination minimum intraperitoneal anticonvulsant doses of citicoline (Tserakson, Nicomed Ferrer Internacional, S.A.) and glutamate АB were determined. To this purpose, citicoline was administered at 500 and 300 mg/kg 1 h prior to PTZ, and glutamate АB was administered at 5 and 2.5 mg/kg 90 min prior to PTZ. Glutamate АB was obtained by hyperimmunization of rabbits with a respective conjugated antigen. In the second series of experiments, AGС was induced by a subcutaneous injection of PTZ 85 mg/kg. To evaluate the effect of the drug combination, the drugs were administered at the minimum effective doses determined in the first series of experiment. Control animals were injected with the same volume of saline in the same experimental conditions. Results. The combination of citicoline and glutamate AB used at minimum effective doses of 300 and 2.5 mg/kg, respectively, did not increase the seizure activity in the brain and enhanced anticonvulsant properties of the drugs in two models of AGС. Conclusion. The combination of citicoline and glutamate AT at minimum effective doses did not increase the convulsive activity in the brain, which supported safety of the drug combination. Besides, this study can serve as an experimental justification for using the drug combination in convulsions to favorably influence cognitive functions and slow progression of neurodegenerative processes.

Anticonvulsant effect of anacardic acid in murine models: Putative role of GABAergic and antioxidant mechanisms

Epilepsy is a neurological disease affecting people of all ages worldwide. Side effects of antiepileptic drugs and their association with oxidative stress stimulate the search for new drugs, which would be more affordable with fewer adverse effects. Accordingly, the aim of the present work is to evaluate the anticonvulsant effect of anacardic acid (AA), a natural compound extracted from cashew liquid (Anacardium occidentalis), in murine models, as well as its antioxidant actions in Saccharomyces cerevisiae. AA (>90% purity) was tested, in vivo, in male Swiss mice (25–30 g) with four convulsive models, (1) pentylenetetrazole, (2) pilocarpine, (3) electroshock, and (4) kainic acid, at doses of 25, 50, and 100 mg/kg, body weight (B.W.) Additionally, the effective dose, toxic dose, and protective index studies were also performed. Results revealed that AA exhibits anticonvulsive effects in models 1, 3, and 4, with a mean effective dose (ED50) of 39.64 (model 1) >100 mg/kg, B.W. (model 2), and 38.36 (model 3); furthermore, AA displays a protection index of 1.49 (model 1), <0.6 (model 2, and 1.54 (model 3). In addition, AA showed antioxidant activities in S. cerevisiae mutated for superoxide dismutases (SOD). In conclusion, these results show that AA exhibits significant anticonvulsant and antioxidant activities and may be used as a promising natural product for the treatment of epilepsy.

Water-Soluble Form of 1-Alkyl(Aryl)Imidazole-4,5-Dicarboxylic Acids. Structure and Anticonvulsant Activity of the Triethanolammonium Salt of 1-Propylimidazole-4,5-Dicarboxylic Acid

Water-soluble forms of a series of 1-alkyl(aryl)imidazole-4,5-dicarboxylic acids were prepared. Anticonvulsant activity of 1-propylimidazole-4,5-dicarboxylic acid and its triethanolammonium salt was studied using the NMDA-induced convulsion model. The triethanolammonium salt of 1-propylimidazole-4,5-dicarboxylic acid was shown to possess anticonvulsant activity whereas the acid itself was a convulsant. The change of pharmacological profile was related to the formation of ion pairs or associates even in polar physiological media. The ability to associate was confirmed using conductivity measurements. An x-ray crystal structure analysis was performed for the triethanolammonium salt of 1-propylimidazole-4,5-dicarboxylic acid.

Relationship between changes in mitochondrial function and hippocampal neuronal apoptosis after recurrent convulsion during developmental stage.

The aim of the present study was to establish a recurrent convulsion model during the developmental stage using inhalation of flurothyl, and to observe the relationship between the changes in mitochondrial function in hippocampal neurons and hippocampal neuronal apoptosis after recurrent convulsion. A total of 36 Sprague-Dawley male rats were selected and randomly divided into the control (NS) group and recurrent-seizure (RS) group for 0, 1.5, 3, 12 and 24 h. After the last seizure the rats were subdivided with 6 animals in each group. Rats in the seizure group inhaled flurothyl repeatedly to induce status convulsivus, 30 min once daily, for 7 consecutive days, while the same operation was conducted in the control group without inhalation of flurothyl. At each time-point after the last seizure, blood was taken from the heart, followed by decapitation and immediate removal of the brain. Half of the brain tissue was immediately fixed in 10% paraformaldehyde to prepare paraffin-embedded tissues for hematoxylin and eosin (H&E) histological staining. Hippocampus was taken from the other half of the brain and stored at −80°C. Changes in mitochondrial membrane potential (ΔΨm) in hippocampal neurons were detected by flow cytometer. Dynamic changes of mitochondrial fusion and division-related genes, mitochondrial fusion protein 2 (Mfn2) and dynamin-related protein 1 (Drp1), in the hippocampus after recurrent convulsion were observed using reverse transcription-polymerase chain reaction (RT-PCR)and western blot analysis. The expression of caspase-3 and cytochrome c (Cyt c) was determined by RT-PCR and western blot analysis. After successful establishment of the recurrent convulsion model in rats during developmental stage using flurothyl, H&E staining results exhibited that in the CA1 region of hippocampus in the NS group, karyopyknosis occurred in nucleus that was stained to be brown and yellow, and the expression peak of apoptotic cells mainly existed at 24 h after the last convulsion. RT-PCR and western analysis revealed that apoptosis-related gene caspase-3 expression in the RS group was elevated at 1.5 h after the last convulsion, and lasted 24 h after convulsion. Detection results of mitochondrial ΔΨm revealed a significant reduction 1.5, 3 and 12 h after convulsion in hippocampal neurons of experimental rats, which reached the trough at 12 h, and rapidly increased after 24 h. The expression of Mfn2 mRNA in the RS group was significantly lower than that in the control group, while the expression of Drp1 mRNA in RS group was distinctly higher than that in the control group. RT-PCR and western blot analysis revealed that, mitochondrial apoptosis-related gene Cyt c expression was increased at 3 h after the last convulsion, and lasted 24 h after convulsion. Correlation analysis showed that the changes in mitochondrial function were closely related to neuronal apoptosis. The results of the study show that apoptosis exists in the hippocampus of rats after recurrent convulsion, which is closely related to the changes in mitochondrial function.

Anticonvulsant evaluation of novel non-imidazole histamine H3R antagonists in different convulsion models in rats

Novel non-imidazole histamine H3 receptor (H3R) antagonists (2–8) were developed and assessed for in-vitro antagonist binding affinities at the human histamine H1–H4R. These novel H3R antagonists (2–8) were examined in-vivo for anticonvulsant effects in three different convulsion models in male adult rats. Compound 6 significantly and dose-dependently exhibited decreased duration of tonic hind limb extension (THLE) in the maximal electroshock (MES)- and fully protected animals against pentylenetetrazole (PTZ)-induced convulsion, following acute systemic administration (5, 10, and 20 mg/kg, i.p.). Contrary, all compounds 2–8 showed moderate protection in the strychnine (STR)-induced convulsion model following acute pretreatment (10 mg/kg, i.p.). Moreover, the acute systemic administration of H3R antagonist 6 (10 mg/kg, i.p.) significantly prolonged latency time for MES convulsions. Furthermore, the anticonvulsant effect observed with compound 6 in MES-model was entirely abrogated when rats were co-injected with the brain penetrant H1R antagonist pyrilamine (PYR) but not the brain penetrant H2R antagonist zolantidine (ZOL). However, PYR and ZOL failed to abolish the full protection provided by the H3R antagonist 6 in PTZ- and STR-models. No mutagenic or antiproliferative effects or potential metabolic interactions were shown for compound 6 when assessing its antiproliferative activities and metabolic profiling applying in-vitro methods. These findings demonstrate the potential of non-imidazole H3R antagonists as novel antiepileptic drugs (AEDs) either for single use or in addition to currently available epilepsy medications.

Neuropharmacological Profile of Fractions of Actaea acuminata H. Hara Roots

The methanol extract of Actaea acuminata roots have been previously reported to exhibit significant antianxiety, anticonvulsant and antidepressant activities. In present study fractionation of crude bioactive methanol extract was carried out using different solvents employing standard procedure. Various fractions were evaluated for antianxiety, anticonvulsant and antidepressant activities using elevated plus maze model (EPM), maximal electroshock-induced convulsions model (MES) and forced / despair swim test (FST) respectively. Successive partitioning of bioactive methanol extract was done with ethyl acetate and 1-butanol. The ethyl acetate fraction (EAF; 100 mg/kg), 1-butanol fraction (BF; 25 mg/kg) and remaining methanol extract (RME; 70 mg/kg) were subjected to neuropharmacological activities. The EAF significantly enhanced entries and average time spent in open arms; significantly decreased duration of MES-induced tonic extension phase and significantly decreased duration of immobility time of rats in comparison to control. BF and RME did not exhibit any neuropharmacological activity. Qualitative chemical tests confirmed presence of alkaloids and polyphenols in EAF. It is finally concluded that alkaloids and/or polyphenols are bioactive constituents of A. acuminata which are responsible for neuropharmacological activities.

Anticonvulsant and Antioxidant Effects of Musa sapientum Stem Extract on Acute and Chronic Experimental Models of Epilepsy.

Background:Musa sapientum (banana) plant extract has been shown to possess antioxidant activity in previous studies. Neuronal injury resulting from oxidative stress is an important factor involved in pathogenesis of epilepsy.Objective:The present study aimed to evaluate the anticonvulsant activity of M. sapientum stem extract (MSSE) in acute and chronic experimental models in mice and its effects on various markers of oxidative stress in the brain of pentylenetetrazole (PTZ)-kindled animals.Material and Methods:Maximal electroshock seizures (MES) and PTZ-induced convulsion models were used for acute studies. For the chronic study, the effect of MSSE on the development of kindling was studied. For the evaluation of the effects of MSSE on oxidative stress in brain, malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the brains of the kindled animals.Results:MSSE significantly increased the latency to onset of myoclonic jerks and the duration of clonic convulsions following PTZ administration. The MSSE pretreated group showed significantly reduced mean seizure score on PTZ-induced kindling. There was a significant increase in the brain MDA levels and decrease in GSH levels in response to PTZ-induced kindling. On MSSE pretreatment, there was a significant decrease in the MDA levels in the brains, though the increase in the GSH levels was not significant.Conclusion:The results from this study suggest the presence of significant anticonvulsant activity in MSSE, in both acute and chronic PTZ-induced seizure models, which could be due to its antioxidant activity, as is reflected by the change in oxidative stress markers in brain.SUMMARY Evaluation of the anticonvulsant activity of Musa sapientum and its effects on various markers of oxidative stress in the brain has not been done previously to the best of our knowledgeM. sapientum stem extract (MSSE) significantly increased the latency to onset of myoclonic jerks and the duration of clonic convulsions in the experimental modelsThe MSSE pretreated group showed significantly reduced mean seizure score on pentylenetetrazole (PTZ)-induced kindlingThere was significant increase in the brain malondialdehyde (MDA) levels and decrease in glutathione (GSH) levels in response to PTZ-induced kindlingOn MSSE pretreatment, there was a significant decrease in the MDA levels in the brain, though the increase in the GSH levels was not significant. Abbreviations Used: MSSE: Musa sapientum stem extract, PTZ: Pentylenetetrazole, MES: Maximal electroshock seizures, MDA: Malondialdehyde, GSH: Glutathione, SOD: Superoxide dismutase, THLE: Tonic hindlimb extension

Evaluation of anticonvulsant activity of Saraca asoca flower (Roxb.) Wilde in Swiss albino mice

Background: Epilepsy is a neurological disorder distressing a large scale of the inhabitants, which accounts for about 1% of the world’s burden of diseases. A large number of groups called antiepileptic drugs are accessible to treat several types of seizures with the objective to decrease seizure incidence and ruthlessness within an outline of an acceptable level of side effects, search for an alternative antiepileptic from natural source, i.e., herbal remedies, which were used traditionally, and safe on human health, is gaining global attention. Aims and Objectives: The objective of the study is intended to evaluate the antiepileptic activity of Saraca asoca flower (Roxb.) Wilde extract of S. asoca flower (ESAF) in Swiss albino mice. Materials and Methods: Ethanolic ESAF was prepared by a continuous method using Soxhlet apparatus with respected temperature. EASF in the doses 50, 100 mg/kg bodyweight along with valproate was administrated to albino mice by oral route followed by antiepileptic activity was evaluated by maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizure models. Abolition of tonic hind limb extension (THLE) phase and increase in seizure latency period, when compared to control group, were taken as a measure of protection in MES- and PTZ-induced convulsion model, respectively. The results are expressed as mean ± standard error of the mean. Statistical analysis was done by one-way analysis of variance test followed by post hoc Dunnett’s multiple comparison tests. P < 0.05 was considered statistically significant. Results: ESAF in the dose of 50 and 100 mg/kg bodyweight showed significant antiepileptic property in both MES and PTZ seizure models. There was significant abolition of THLE phase in MES model. There was also significant increase in seizure latency in PTZ-induced seizure model. Conclusion: ESAF possesses significant antiepileptic activity. Further, investigations are required to determine its active constituents and also its mechanism of action.

Chrysin isolated from Pyrus pashia fruit ameliorates convulsions in experimental animals

Objective: The traditional use of the ethanolic extract of the fruit of Pyrus pashia (EPP) as a potential anticonvulsant was validated using experimental animal models. Furthermore, the anticonvulsant activity of isolated chrysin was investigated against experimental animal models to draw a possible therapeutic mechanism of EPP. Additionally, the safety profile of chrysin was evaluated to explore the possible therapeutic alternative in the management of epilepsy.Method: The anticonvulsant activity in terms of duration of onset of hind limb tonic extension and convulsion of standardized EPP was evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) model of experimental epilepsy respectively. Furthermore, the anticonvulsant activity and electrophysiological properties of chrysin was investigated in addition to antioxidant activity against PTZ-induced convulsion in experimental animals. Moreover, the neurotoxic profile of the chrysin was assessed in terms of duration of movement and running in photoactometer and rotarod apparatus, respectively.Results: EPP (100, 200, and 400 mg/kg) exhibited significant anticonvulsant activity against an acute model of MES and PTZ-induced convulsions in experimental animals. Furthermore, chrysin (2.5, 5, and 10 mg/kg) also exhibited significant anticonvulsant activity against PTZ-induced convulsions in rats. In addition, chrysin did not exhibit sedative-like behavior in experimental rodents.Discussion: EPP could be considered as a potential and alternative therapeutic option in the management of epilepsy.