Tonic Extension Research Articles

Antiseizure Activity of Mitragyna inermis in the Pentylenetetrazol-Induced Seizure Model in Mice: Involvement of Flavonoids and Alkaloids.

This study aimed to investigate whether Mitragyna inermis (Willd.) Otto Kuntze organic and aqueous extracts are able to control seizures induced by pentylenetetrazol (PTZ) in mice based on flavonoid fingerprints and alkaloidal contents. Ethanolic extract and decoction-derived fractions from roots, leaves, and stems were subjected to chromatographic fingerprinting using AlCl3 and screening for their antiseizure effects using PTZ-induced acute seizure model. From the fractions that showed potent bioactivities, plausible antiseizure alkaloids were isolated using thin layer chromatography, and their structures were elucidated using 1H NMR, 2D NMR, 13C NMR, and FAB-HR (+ve or -ve). All fractions, with the exception of the dichloromethane and hexane fractions, revealed remarkable flavonoid fingerprints. An acute PTZ-induced seizure test revealed that ethanolic extract of stem bark [500 mg/kg body weight (bw)], ethyl acetate extract of stem bark (500 mg/kg bw), and aqueous extract of leaves (300 mg/kg bw) significantly delayed the occurrence of hind limb tonic extension (HLTE); however, a non-significant delay was observed in the onset of first myoclonic jerk compared with control animals. Isolation yielded four main alkaloids: that are, pteropodine (1), isopteropodine (2), mitraphylline (3) and corynoxeine (4). Corynoxeine is a new compound derived from M. inermis. This study suggests that flavonoid fingerprints are tracers of M. inermis anticonvulsant ingredients. The stem bark ethanolic and ethyl acetate extracts and leaf aqueous extracts contain anticonvulsant bioactive principles that delay notifying the HLTE occurring in male naval medical research institute mice. Furthermore, alkaloidal contents also remain plausible bioactive anticonvulsant principles. All observations support the traditional use of M. inermis to manage epilepsy. However, further studies are needed to understand the effects of alkaloid fractions, flavonoids, and the isolated compounds as promising antiseizure agents derived from M. inermis in experimental animals.

Anti-Convulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.-Ham. Ex D.Don (Lamiaceae) in Mice.

The leaves of Ajuga integrifolia Buch.-Ham. ex D.Don (Lamiaceae) have long been used as an anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting their use is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant. The anti-convulsant activity of the extract was investigated in both acute (pentylenetetrazol [PTZ], 80 mg/kg; and maximal electroshock [MES]) and chronic (PTZ, 35 mg/kg) kindling seizure models. For the experimental paradigms, various doses of the extract (100, 200, and 400 mg/kg) were administered. Positive controls received sodium valproate (200 mg/kg) for the PTZ model and phenytoin (25 mg/kg) for the MES model. Parameters including the onset of clonus and duration of hindlimb tonic extension were recorded and compared with controls. Moreover, the total alkaloid, flavonoid, and phenol contents of the extracts were determined. Ethyl acetate extract produced a superior effect among all solvent extracts in both the PTZ and MES models. At all doses, it significantly delayed the mean onset of clonus (p<0.01) in the PTZ test compared to controls. It also significantly reduced (p<0.001) the mean duration of hindlimb tonic extension in the MES model. Treatment of mice with 200 mg/kg (p<0.01) and 400 mg/kg (p<0.001) of ethyl acetate extract significantly protected against PTZ-induced kindling compared to controls. The leaf was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045±0.8445 mg quercetin equivalent per gram of dry extract of flavonoids, and 21.928±1.118 mg gallic acid equivalent per gram of dry extract of phenols. This study indicated that the plant A. integrifolia has anti-convulsant activity in both acute and chronic models of seizure. This plant represents a potential source for the development of a new anti-epileptic drug for pharmacoresistant epilepsy.

PHARMACOLOGICAL AND PHYSICO-CHEMICAL PROPERTIES OF COMPOSITIONS BASED ON BIOSURFACTANTS AND N-CONTAINING HETEROCYCLIC DERIVATIVES OF 1,4-NAPHTHOQUINONE

Composite preparations based on rhamnolipid biosurfactants and N-containing heterocyclic 1,4-naphthoquinone derivatives were obtained. The formation of the compositions was confirmed by UV spectroscopy, dynamic light scattering and changes in the surface tension of the compositions in comparison with the original solutions. Physicochemical and biological properties of composite drugs have been studied. The anticonvulsant effect was assessed using the pentylenetetrazole (PTZ) model. Doses of PTZ for induction of clonic-tonic seizures (DCTC) and tonic extension (DTE) were calculated relative to control. The effect of rhamnolipid on increasing the permeability of cell membranes for compounds 1a-e was evaluated indirectly by studying anticonvulsant activity. Compound (2-chloro-3-((3-(p-tolyl)-1H-pyrazol-5-yl)amino) naphthalene-1,4-dione) (1b) in combination with rhamnolipid was found to have a higher anticonvulsant activity DCTC and DTE averaged 239% and 244%, respectively, which may indicate an improvement of the penetration of the compound when in complex with rhamnolipid into the cell and as a result, an increased anticonvulsant activity of the composite drug.

Evaluation of Anticonvulsant Activity of Hydro Ethanolic Extract of Coccinia grandis in Mice

Background: Hydro ethanolic extract of Coccinia grandis leaves was assumed to have anticonvulsant activity. Objective: To evaluate the anticonvulsant activity of Coccinia grandis by using some animal models like maximal electric shock model, pentylenetetrazole induced seizures, Isoniazid induced seizures. Materials and Methods: Various equipment and apparatus were used in the present study. Hydroethanolic extract of Coccinia grandis was done by Soxhlet apparatus. Phytochemical investigation of the leaf extract of Coccinia grandis was performed. Anticonvulsant activity was determined by using different animal models like maximal electric shock model, pentylenetetrazole induced seizures, Isoniazid induced seizures. Results: Anticonvulsant activity was determined by using different animal models like Maximal electric shock model, pentylenetetrazole induced seizures &amp; Isoniazid induced model. Percentage of protection, Duration of hind limb tonic extension (HLTE), Latency of onset of convulsions were taken as a indication of anticonvulsant activity. Phenytoin and Diazepam showed significant anticonvulsant activity. In the present study the test samples exhibited significant (P &lt; 0.0001) anticonvulsant activity and antioxidant activity at a dose of 200,400mg/kg. It may due to the presence of alkaloids, Phenols, carbohydrates, glycosides, saponins and flavonoids terpenoids. Conclusion: In present study leaves of Coccinia grandis extract was collected and anticonvulsant activity was examined in a doses of 200mg/kg, 400mg/kg. The results clearly shown that the low dose 200mg/kg of plant extract shown appropriate anticonvulsant activity and the high dose 400mg/kg shown specific anticonvulsant activity when compared to control and standard groups.

Effects of Ethanolic Root Extract of Clitoria ternatea against Experimentally Induced Convulsions and Anxiety in Rodents

In animal models for screening for anticonvulsant activity, it has been scientifically established that medicinal herbs used in traditional medicine for the treatment of epilepsy possess promising anticonvulsant properties and can be a source of newer anticonvulsants. This study's objective was to evaluate the ethanolic root extract of Clitoria ternatea Linn for its preliminary phytochemical components, anticonvulsant, and anxiolytic effects. Anticonvulsant activity was evaluated against Maximum electroshock (MES) induced convulsion and pentylenetetrazole (PTZ)-induced convulsion model in rats. Using phenytoin (25 mg/kg) as a standard drug, the efficacy of the extract at oral dose levels of 200 and 400 mg/kg were evaluated in an experimental rat model. The marble bury test was used to assess the mice for anxiolytic activity, and lorazepam served as the standard drug at a dose of 0.05 mg/kg. Phytochemical screening revealed that C. ternatea extract contain carbohydrates, flavonoids, alkaloids, proteins, triterpenoids, phenols and steroids. The ethanolic extract significantly decreased the duration of tonic flexion and tonic extension in MES induced model (p&lt;0.05). The ethanolic extract significantly increased the latency of convulsion and decreased the duration of convulsion in PTZ induced model (p&lt;0.05). The ethanolic root extract were found to be significantly decrease the number of marbles buried in the treated groups as compared to control group, indicating anxiolytic activity. According to specific investigations, terpenes and steroids exhibited anticonvulsant effects in some experimental seizure models, including MES and PTZ. Alkaloids and triterpenes, which are phytoconstituents in ethanolic extract of Clitoria ternatea (EECT), might be the basis of its anxiolytic actions. Based on the findings of the study, Clitoria ternatea's ethanolic root extract has anticonvulsant and anxiolytic effects on animals.

Sedative and anticonvulsant activities of aqueous and ethanol dried leaf extracts of Solenostemon monostachyus in mice

This study evaluated the sedative, and anticonvulsant activities of the aqueous (AESM) and ethanol (EESM) dried leaf extracts of Solenostemon monostachyus. The sedative effect of the extracts was evaluated with ketamine-induced hypnosis (100 mg/kg, i.p.). Also, the anticonvulsant activity was evaluated using pentylenetetrazole (PTZ)-induced convulsion (85 mg/kg, i.p.), strychnine-induced convulsion (2 mg/kg, i.p.) and maximal electroshock (MES)-induced convulsion models. The AESM (200 mg/kg, p.o.) gave 66.67% protection, while EESM (800 mg/kg, p.o.) gave 100% protection against the hind limb tonic extension on the MES. The AESM only at 200 mg/kg, p.o. caused a significant change (p &lt; 0.01) in the convulsion latency and time of death in PTZ –induced convulsion. The AESM and EESM (200, 400 and 800 mg/kg, p.o.) significantly (p &lt; 0.05 – 0.01) shortened sleep latency. At 400 and 800 mg/kg, p.o., AESM prolonged (p &lt; 0.05) total sleeping time while EESM at 800 mg/kg, p.o. significantly (p &lt; 0.05) prolonged total sleeping time relative to vehicle. The study concluded that the aqueous leaf and ethanol dried leaf extracts of S. monostachyus possessed sedative and mild anticonvulsant activities.

Anticonvulsant Activity of Lacidipine against Mes- and Ptz-Induced Seizures

Epilepsy is one of the challenging medical conditions affecting neonates, children and elderly. It has affected 1710 to 9780/million populations within India. Although the report of this condition dates to the prehistoric era, drugs for its treatment are not 100% effective and more often lead to toxic effects. Therefore, a potent drug or a drug adjunct is the need-of-the-hour for providing effective control for this neurological condition. The aim of the present study is to evaluate lacidipine, a calcium channel blocker as a protective agent in seizures induced by standard models of epilepsy, namely maximal electroshock seizure model (MES) and Pentylenetetrazole (PTZ). Standard methods for the induction of seizures such as MES and PTZ were performed on male Wistar albino mice. The mice were then treated with vehicle/standard drug (sodium valproate)/ lacidipine. Further, the standard parameters of recovery duration were evaluated. The study revealed that lacidipine at a dose of 3mg/kg body weight significantly reduced the duration of hind limb tonic extension and postictal depression in MES. PTZ-induced seizures showed significantly reduced mean duration of hind limb tonic flexion, hind limb tonic extension, clonus and postictal depression. The findings from the present study suggest that lacidipine has potent anticonvulsant ability in better protection against MES-induced seizures over that of the PTZ-induced one.

Ilae classification of seizures and antiepileptic medications apothegmatic: hereafter advancement and clinical practice

Introduction: The Antiepileptic medications are frequently categorized into divisions such as ‘first-generation’ (i.e., carbamazepine, phenobarbital, phenytoin, primidone, and valproate) and ‘second-generation’ (lamotrigine, levetiracetam, felbamate, gabapentin, topiramate, tiagabine, oxycarbazepine, zonisamide, and pregabalin). Chronic phenytoin ingestion leads to its impact in the cerebral cortex, resulting in atrophy of cerebellum, cause ataxia and nystagmus. Objective: To recapitulate the International league against epilepsy classifications, first treatment for epilepsy based on their classifications, antiepileptic medications adverse drug reaction, Methodology: The author used 74 distinctive published articles for the accomplishment of this review article. Google search engine was used for accessing published articles from databases like Google Scholar, Research Gate, PubMed, NCBI, NDSS, PMID, PMCID, Cochrane Database and CLINMED international library. Findings: Tonic-clonic is characterized by stiffness for loss of consciousness occurred by tonic extension and rhythmic clonic contractions of all considerable muscle groups. Antiepileptic drugs are implicitly an effective treatment for patient with epilepsy. Carbamazepine cause serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis and stevens-johnson syndrome, aplastic anemia and agranulocytosis, Suicidal Behavior and Ideation, Stevens johnson syndrome, cholestatic jaundice, ataxia, xerostomia, speech disturbances, feeling sleepy Conclusion: Commonly happening side-effects of AEDs are memory troubles, exhaustion, tremors, gastrointestinal symptoms, osteoporosis, depression, drowsiness, dizziness, weight change, nausea. In generalized seizures, on the other hand, the seizure is generalized from the endeavor (i.e., primary generalized seizures), launching in both hemispheres of the brain contemporaneously

Preliminary assessment of proanthocyanidin isolates of Vitis vinifera seed on the central nervous system of male Albino mice

This study evaluated the potential neurobehavioral effects of proanthocyanidin-rich-fraction (PRF) obtained from Vitis vinifera seed in male Albino mice.Adult (2½- to 3-month old) male Albino mice were treated with PRF (200, 100, 50 mg/kg) and subjected to diverse behavioral models specially designed for the assessment of central nervous system-acting agents.One-shot intraperitoneal (i.p) injection of PRF (200 and 100 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing, and grooming), anxiety-like responses (% open-arm time, open-arm entries but decreased the total number of enclosed arm times). However, acute i.p administration of PRF decreased the total score of apomorphine-induced stereotyped behaviors, latency to hexobarbitone-induced sleep, and increased the total sleep duration. Moreover, indices of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) were decreased in the PRF treatment groups, especially the PRF (50 mg/kg)-treated mice.Based on these present findings, it could therefore be inferred that systemic administration of PRF of V. vinifera seed origin induces diverse modification on the behaviors of the treated mice stemming from anxiolytic, anticonvulsant, sedative, and decrease in core temperature.

EVALUATION OF PHARMACOLOGICAL EFFECT OF CASSIA SOPHERA LINN LEAVES EXTRACTS

Instroduction: Cassia sophera Linn (C. sophera) is a medicinally important plant belonging to the family of Caesalpiniaceae. The whole part of the plant is used as traditional folk medicine and is reported to possess analgesic, anticonvulsant, antioxidant, anti-inflammatory, hepatoprotective and antiasthmatic activity.&#x0D; Materials and Methods: Eddy’s hot plate and Analgesiometer tests were used to asses the antinociceptive activity of Cassia sophera. Pentobarbitone narcosis potentiation test was used to evaluate the hypnotic and sedative effect, while anticonvulsant activity was evaluated by Maximum electroshock-induced seizure test and Pentylenetetrazol induced seizure test.&#x0D; Results and Discussion: Test drug (440 mg/kg) produced significant analgesia, potentiated the pentobarbitone induced sleeping time and exhibited anticonvulsant effect against hind limb tonic extension phase of maximum electroshock-induced seizure test and seizures induced by pentylenetetrazol.&#x0D; Conclusion: The preliminary screening of seed extract of Cassia sophera, Linn. exhibited analgesic, anticonvulsant effects and potentiated pentobarbitone sleeping time. The ethanol extract of seed of Cassia sophera, Linn. deserves further investigation to elucidate the mechanisms of action.

Anticonvulsant and antioxidant effect of hydroalcoholic extract of Valeriana wallichii rhizomes in acute and chronic models of epilepsy in albino rats

Oxidative stress plays an important role in the aetiology of seizure-induced neuronal death. The present study was aimed to evaluate the anticonvulsant and antioxidant activity of hydroalcoholic extract of Valeriana wallichii (HAEVW) rhizomes in albino rats. Flavonoids possess a potent anticonvulsant effect through modulation of GABA/BDZ receptor and neuroprotective effect by regulating oxidative stress in PTZ-induced convulsion. Total phenolics and flavonoids content of HAEVW rhizomes were measured and the anticonvulsant activity was evaluated using PTZ and MES induced convulsion models. The in-vivo antioxidant activity was evaluated using the PTZ-kindled model by estimating brain malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and nitric oxide (NO). It was observed that the flavonoids content of the extract was 80% of the total phenolics content and HAEVW (200 and 400 mg/kg) showed a significant (P <0.01) delay in onset, decrease in duration of tonic convulsion and hind limb tonic extension (HLTE) in PTZ and MES induced convulsion respectively. In the PTZ-kindling model, HAEVW rhizomes (400 mg/kg) restored the MDA and all antioxidant parameters to normal except NO. It was concluded that flavonoids of rhizomes of V. wallichii may be responsible for the anticonvulsant and antioxidant activity of the extract.

The Activities of the Central Nervous System Following Ethyl Acetate Extract of Mucuna pruriens Seed Administration in Male BALB/c Mice

A number of reports showed the beneficial psychotropic effects of many of the Nigerian medicinal plants, but few scientific studies have been carried out as empirical evidence. This study investigated the possible neurobehavioural effects of ethyl acetate extract of Mucuna pruriens (MP) seed in male BALB/c mice. Male BALB/c mice (2½-3 months old) were grouped into 5 (n=6), treated with normal saline (0.1 mL), n-propanol extract of MP (200, 100, 50 mg/kg) or reference drug haloperidol (HP) or diazepam (DZP); thereafter, subjected to diverse behavioural models to evaluate the central nervous system (CNS) effects of the extract. A bolus of MP (200, 100, and 50 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing and grooming), anxiety-like responses (% open-arms time, open-arm entries, and the total number of enclosed arms times). Additionally, a one-shot of intraperitoneal administration of MP decimated the total score of apomorphine-induced stereotyped behaviours. Latency to hexobarbitone-induced sleep increased significantly in the 200 mg/kg MP, unchanged in the 100 mg/kg MP, and decreased in the 50 mg/kg MP treated groups. There was a marked decrease in the markers of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) following MP treatment, especially the higher doses (200 mg/kg and 100 mg/kg). In conclusion, the CNS effects of systemic administration of MP seed are not unrelated to its hypothermic, hypnotic, anxiolytic, and anticonvulsant effects.

Evaluation of Antiepileptic Activity of Flowers of Cocos nucifera L. Against Experimentally Induced Convulsions in Rats

The report used to be planned to analyze the antiepileptic activity of Cocos nucifera flowers against special experimentally induced convulsions in rats. In the present study, antiepileptic activity was assessed by following experimental models. Anti-convulsant in vivo models: Maximal electroshocks (MES) induced models in rats, Pentylenetetrazole (PTZ) induced in rats. Pretreatment of animals with Cocos nucifera flowers extract has reduced by half the general continuance of tonic hind leg extension, the most commonly used endpoint in assessing clonic convulsions. MES provokes repetitive neuronal firing indicates epileptic neurons. MES is the widely accepted model to demonstrate the antiepileptic property of a drug. This property is antagonistic of the plant extract could flow from to blockade of voltage-gated sodium channel or due to effect on NMDA receptors. The Cocos nucifera flowers extract was also demonstrated potential anticonvulsant activity in PTZ induced convulsions and this may be due to its agonistic activity on the GABAA receptor. This is further supported by an elevated level of GABA by the plant extract in the PTZ model. Methanolic extract of Cocos nucifera flowers has shown significant anticonvulsant activity against MES and Pentlylenetetrazole induced convulsion models. This observed activity could also be the referable presence of flavonoids and other phytochemical constituents found in the powerful extract.&#x0D; Keywords: Cocos nucifera, antiepileptic activity, Maximal electroshock, Pentlylenetetrazole, Flavonoids,

EVALUATION OF ANTICONVULSANT ACTIVITY OF CALLISTEMON CITRINUS (CURTIS) SKEELS (MYRTACEAE) VOLATILE OIL

The use of medicinal plants is on the rise due to the increase of various diseases and shortcomings of orthodox medicine. For many ailments including convulsion, conventional medicine has not been able to find a lasting solution. This study was directed towards assessing the ethnomedicinal use of Callistemon citrinus leaves in the management of convulsion. The volatile oil of the leaves was extracted and an acute toxicity test was carried out following Lorke’s description. Maximal electroshock (MES), strychnine and pentylenetetrazol anticonvulsant methods were used. Separate groups of albino mice were given 200, 400 and 800 mg/kg doses of the volatile oil. Drug solutions; 30 mg/kg phenobarbitone for MES and 2 mg/kg diazepam for strychnine and pentylenetetrazol models were administered as a positive control. The start of tonic leg extension, duration and percentage mortality was recorded. Doses of 200 and 400 mg/kg significantly (P&lt;0.05) inhibited seizure in the mice with scores of 40 % each in the MES model. There was a dose-dependent reduction in the duration of seizures with 68.47, 70.27 and 81.08 % reductions in the pentylenetetrazol model. No significant coverage was given in the strychnine model. C. citrinus oil protected the mice against pentylenetetrazol and maximal electroshock-induced convulsion hence could contribute to the medical treatment of epilepsy.

Cannabis Sativa: A Remedy for Convulsion by Inhibition of GABAA Receptor and Significantly Delayed Onset of Seizure Latency and Death - An Experimental Validation and Molecular Docking

This study aimed to investigate the anticonvulsant potentials of Cannabis sativa and its possible mechanism using the in vivo and in-silico models. A total of 20 male albino mice was used for this study and were divided randomly into five groups. Group 1 as negative control receiving 0.2ml 0f 10% ethanol only, and groups 2 and 3, received 200mg/kg/ body weight low dose of C. Sativa extract and 400mg/kg bw low dose of C. sativa extract, while groups 4 received 50 mg/kg body weight of phenobarbitone and group 5 received 50 mg/kg body weight of phenobarbitone+ 200 mg/kg body weight of the extract. Administration of C. Sativa extract was done via orogastric feeding; GABA-ergicseizure, was induced by administration of 80 mg/kg/bodyweight of Pentylenetetrazole (PTZ) via the intra-peritoneal route to all the groups. This was done about thirty minutes after the administration of treatment agents. Each animal was observed individually for one hour to determine the onset of muscular jerks and tonic hind limb extensions and death. Animal study results revealed that C. sativa may likely possess’ anticonvulsant potentials as It is significantly seizure latency and death in PTZ treated mice. For the in silico studies, about 49 compounds of C. sativa were obtained from the PubChem library and were docked on various targets site of proteins; Glutaminase, 4-Aminobtyrate Aminotransferase, Perioxisome proliferator Activated receptor (PPAR), Succinic semialdehyde dehydrogenase, Gama amino butyric acid –A receptor (GABA-A), Histone deacetylases (HDAC), Phosphoribosyl pyrophosphate amido transferase and human GAFT-1. Furthermore, the in-silico study revealed that compounds like Cannabisin A and D showed anticonvulsant potential activation of GABA.

Anticonvulsant activity of methanolic extract of Withania cogulans in mice

Mental and neurological diseases including depression, Parkinson's disease, dementia, epilepsy, anxiety disorders and bipolar disorders account for a considerable amount of the world's disease burden. Unfortunately, drugs used in the treatment of neurological diseases are expensive, symptomatic and they produce undesirable side effects. People from different cultures prefer to use medicinal plants for the treatment of various ailments ranging from plain to perplex disorders because they are most affordable, cost effective and easily accessible source of treatment in the primary healthcare system throughout the world. Withania coagulans, an erect grayish under-shrub belongs to family Solanaceae. It is common in Pakistan, East India, Iran and Afghanistan. The objective of this study was to analyze the anti-seizure activity of crude methanolic extract of Withania coagulans fruits (MeWc). For screening of this activity, maximal electroshock seizures model (MES) and chemically-induced seizures models were used. In maximal electroshock seizures test MeWc showed significant dose dependent percent protection against hind-limb tonic extension; significant and dose-dependent increase in latency to myoclonic jerks and tonic clonic convulsions and decrease in seizures duration were observed in PTZ-induced seizures. In strychnine-induced convulsions MeWc significantly increased latency to hind-limb tonic extension and percent protection from death in a dose-dependent manner. Thus, it was inferred from the experiments that extract of Withania coagulans showed anticonvulsant activity.

The effects of febrile status epilepticus on hippocampal circuit function

Rationale . Febrile status epilepticus (FSE) in children has been linked to cognitive deficits and epileptogenesis later in life. Recent evidence in the experimental hyperthermia animal model of FSE (eFSE) has shown that spatial memory deficits may be a result of structural and functional changes to specific cells types in the hippocampal circuit. Experimentally, the effects of FSE on cognitive deficits are mitigated by the blockade of neuron-restrictive silencing factor (NRSF) binding to its target chromatin. The goal of the current study is to understand the relationship between cognitive outcomes and the efficacy of hippocampal circuit throughput and whether this relationship is altered by NRSF treatment post FSE. Methods . Postnatal day 10–11 male Sprague-Dawley rat pups (N = 13) underwent procedures for eFSE hyperthermia induction. Pups were placed, two at a time, inside a 3 L flask, the bottom of which was lined with absorbent paper. Prior to hyperthermia, a glycerin-based hydrating ointment was applied to the paws, ears, and tail of the pups to mitigate potential hyperthermic skin injury. Pups were subjected to a continuous stream of warm air until hyperkinesis and chewing automatisms were identified. Seizure behaviors typically progressed to clonic movements and eventual tonic extension. After approximately 60 min of hyperthermia, eFSE pups were immersed in cool water (−23.0 °C) to aid in the return of core temperature to normothermia and to promote seizure cessation. Pups were then placed on a euthermic pad maintained at 37 °C for 30 min, and then were returned to their home cage and dam. An intact NRSE or a scrambled (SCR) NRSE sequence oligodeoxynucleotide (ODN) was infused ICV 3 h post eFSE (Sigma-Aldrich). Four experimental groups were used in these experiments. The first was a non-eFSE control animal that received a scrambled sequence of NRSE (CTL-SCR). The second was a non-eFSE control who received the NRSE sequenced ODN (CTL-NRSE). The third were eFSE animals infused with scrambled ODN (eFSE-SCR). Finally, there was a group of eFSE animals infused with NRSE ODNs (eFSE-NRSE). 2.5 nmol of either NRSE or SCR ODN were infused bilaterally into the ventricles at a rate of 0.5 l/min and a volume of 2.5 l/hemispheres. ICV infusions were repeated 24 h after eFSE. While blind to treatment group, treated and untreated rats were trained on an active avoidance spatial task on a rotating arena in order to measure cognitive outcomes in relation to treatment condition. To measure circuit throughput in the dorsal hippocampus across experimental conditions, we utilized 64-channel silicon probes to measure EEGs and neuronal action potentials across synaptic input regions along the apical and basal dendrites of CA1 pyramidal cells and dentate gyrus granular cells under urethane-anesthesia. Following acute probe recording experiments, animals were perfused with fixative and brain tissue was harvested for immunohistochemical procedures. Results . Preliminary data suggests group differences in the ability to learn the active avoidance spatial task while analysis of cell spiking data suggests interhemispheric differences in neuronal activity across all groups. Acute recordings also revealed that there were notable hallmarks during EEG recordings across animals and groups in theta-, beta-, and gamma- range oscillations in deep CA1; dentate gyrus EEGs; and also the response to mechanical perturbation when the probe was lowered.

Association between semiologic, autonomic, and electrographic seizure characteristics in children with generalized tonic-clonic seizures

IntroductionGeneralized tonic-clonic seizures (GTCS) are associated with elevated electrodermal activity (EDA) and postictal generalized electroencephalographic suppression (PGES), markers that may indicate sudden unexpected death in epilepsy (SUDEP) risk. This study investigated the association of GTCS semiology, EDA, and PGES in children with epilepsy. MethodsPatients admitted to the Boston Children’s Hospital long-term video-EEG monitoring unit wore a sensor that records EDA. We selected patients with at least one GTCS and reviewed video-EEGs for semiology, tonic and clonic phase duration, total clinical seizure duration, electrographic onset, offset, and PGES. We grouped patients into three semiology classes: GTCS 1: bilateral symmetric tonic arm extension, GTCS 2: no specific tonic arm extension or flexion, GTCS 3: unilateral or asymmetrical arm extension, tonic arm flexion or posturing that does not fit into GTCS 1 or 2. We analyzed the correlation between semiology, EDA, and PGES, and measured the area under the curve (AUC) of the ictal EDA (seizure onset to one hour after), subtracting baseline EDA (one-hour seizure-free before seizure onset). Using generalized estimating equation (GEE) and linear regression, we analyzed all seizures and single episodes per patient. ResultsWe included 30 patients (median age 13.8 ± 3.6 years, 46.7% females) and 53 seizures. With GEE, GTCS 1 was associated with longer PGES duration compared to GTCS 2 (Estimate (β) = −26.32 s, 95% Confidence Interval (CI): −36.46 to −16.18, p < 0.001), and the presence of PGES was associated with greater EDA change (β = 429604 μS, 95% CI: 3550.96 to 855657.04, p = 0.048). With single-episode analysis, GTCS 1 had greater EDA change than GTCS 2 ((β = −601339 μS, 95% CI: −1167016.56 to −35661.44, p = 0.047). EDA increased with PGES presence (β = 637500 μS, 95% CI: 183571.84 to 1091428.16, p = 0.01) and duration (β = 16794 μS, 95% CI: 5729.8 to 27858.2, p = 0.006). Patients with GTCS 1 had longer PGES duration compared to GTCS 2 (β = −30.53 s, 95% CI: −44.6 to −16.46, p < 0.001) and GTCS 3 (β = −22.07 s, 95% CI: −38.95 to −5.19, p = 0.016). ConclusionIn children with epilepsy, PGES correlates with greater ictal EDA. GTCS 1 correlated with longer PGES duration and may indirectly correlate with greater ictal EDA. Our study suggests potential applications in monitoring and preventing SUDEP in these patients.

Synthesis, Molecular Docking, and Biological Evaluation of Some Novel 2- (5-Substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole Derivatives as Anticonvulsant Agents.

Benzothiazole is an organosulfur heterocyclic compound that has a considerable place in drug discovery due to significant pharmacological actions. The main objective of the present study was to synthesize some novel 2-(5-substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole derivatives and evaluate them for their anticonvulsant activity using in silico and in vivo methods. A set of sixteen 2-(5-substituted 1, 3, 4-oxadiazole-2-yl)-1, 3-benzothiazole derivatives were prepared using multi-step reactions starting from o-amino-thiophenol and characterized by suitable spectral techniques. The synthesized compounds were evaluated for anticonvulsant activity using in silico and in vivo methods. In silico molecular docking study was performed using Molegro Virtual Docker software to analyze binding modes of compounds with the internal ligand of PDB ID: 1OHY and 1OHV; and in vivo pharmacological activities were tested for both generalized tonic-clonic seizures and generalized absence (petit mal) seizures using Maximal Electrical Shock and PTZ-induced seizure models, respectively. Some new 2-(5-substituted-1,3,4-oxadiazole-2-yl)-1,3- benzothiazole (5a-5p) were successfully synthesized by finally refluxing 1, 3-benzothiazole-2-carboxyhydrazide with different aromatic acids in phosphoryl chloride. Docking results showed that compounds 5c, 5j, and 5m were found to have the highest number of H-bond interactions; i.e. 4, 4, and 7 respectively with target proteins 1OHY and 6, 3, and 4 respectively with target protein 1OHV, whereas phenytoin showed only two H-bonding with both proteins. In the Maximal electroshock seizure method, the synthesized compounds 5h, 5k and 5o demonstrated potent anticonvulsant activity against the tonic seizure with a significant decrease in tonic hind leg extension period with a mean duration of 7.9, 7.4, and 7.0 sec respectively, as compared to the other synthesized compounds. In contrast, in the PTZ-induced seizure model, compounds 5c, 5h, and 5m showed protection against clonic convulsion with significant elevation in the onset time of clonic convulsion at 311.2, 308.0, and 333.11 sec, respectively. Thus, from the results, it can be concluded that compound 5h, a benzothiazole derivative endowed with an oxadiazole ring, can be developed as a potential anticonvulsant agent.

Evaluation of Anticonvulsant Activity of Kochia Scoparia L. Schrad (Amaranthaceae) Volatile Oil

Background: Epilepsy is one of the most common serious neurological disorders. Most antiepileptic or anticonvulsant drugs do not prevent or reverse the pathological process that underlies epilepsy, hence the continuous search for new therapeutic agents with minimal side effects and greater efficacy.Objective: The objectives of this study were to determine the acute toxicity profile and investigate the anticonvulsant activity of volatile oil of Kochia scoparia (Amaranthaceae ).Method: Volatile oil was extracted from fresh leaves of K. scoparia through hydrodistillation process, using a Clavenger-type apparatus. Acute toxicity testing was done using Lorke’s method. The anticonvulsant models used were pentylenetetrazol, strychnine and maximal electroshock. Albino mice were randomly divided into five groups (n=5). Group I (control group) was given 0.2 ml each of water orally while groups II, III and IV received 75, 150 and 300 mg/kg of the volatile oil. Group V received the standard drug solution; 30 mg/kg phenobarbitone for Maximal electroshock and 2 mg/kg diazepam for pentylenetetrazol and strychnine models. The onset of tonic leg extension, duration and protection from mortality were noted.Results: Sub acute toxicity test revealed that doses above 1000mg/kg of the volatile oil is toxic. Doses of 75, 150 and 300 mg/kg significantly (P&lt;0.05) protected the mice against seizures with scores of 20, 20 and 40 % respectively in both Maximal electroshock and pentylenetetrazol induced convulsion models. No protection was offered in strychnine induced convulsion model; P &gt; 0.05.Conclusion: The volatile oil of K. scoparia could be useful in the management of epilepsy.