Latency Of Convulsions Research Articles

Pharmacological Evaluation of Sedum lineare Thunb Extract: Acute Toxicity and Anticonvulsant Effects in Swiss Albino Mice

Aim: This study aimed to assess the acute toxicity and anticonvulsant effects of the hydroalcoholic extract of Sedum lineare Thunb in Swiss albino mice. Materials and Methods: Acute toxicity was evaluated by administering a high dose (2000 mg/kg) of the hydroalcoholic extract and monitoring mortality, behavioral changes, body weight, and food/water consumption. Hematological parameters and organ histopathology were analyzed to assess systemic effects. The anticonvulsant activity was explored using pentylenetetrazole (PTZ) and picrotoxin-induced seizure models at various extract doses (100, 250, and 500 mg/kg). Results and Discussion: The acute toxicity study revealed the safety of the hydroalcoholic extract, with no observed mortality, behavioral changes, or adverse effects on body weight and food/water consumption. While hematological changes were statistically significant, their clinical relevance requires further exploration. Histopathological examination confirmed the absence of organ toxicity. In the anticonvulsant assessment, the hydroalcoholic extract exhibited a protective effect against PTZ-induced seizures, significantly delaying jerk onset at the highest dose. Although not prevent clonic convulsions entirely, it dose-dependently reduces mortality rates. In the picrotoxin model, particularly at 250 mg/kg, the extract significantly increased clonic convulsion latency and suppressed mortality, indicating a potential modulatory role against seizures. Conclusion: The hydroalcoholic extract of S. lineare Thunb demonstrated favorable acute toxicity and promising anticonvulsant effects in Swiss albino mice. The observed hematological changes warrant further investigation for clinical relevance, and additional studies, including long-term assessments and biochemical analyses, are recommended to comprehensively evaluate the extract’s safety and therapeutic potential. These findings support further exploration of S. lineare Thunb as a potential candidate for neurological disorder interventions..

In Vivo Evaluation of Self-assembled nano-Saikosaponin-a for Epilepsy Treatment.

Saikosaponin-a (SSa) exhibits antiepileptic effects. However, its poor water solubility and inability to pass through the blood-brain barrier greatly limit its clinical development and application. In this study, SSa-loaded Methoxy poly (ethylene glycol)-poly(ε-caprolactone) (MePEG-SSa-PCL) NPs were successfully prepared and characterized. Our objective was to further investigate the effect of this composite on acute seizure in mice. First, we confirmed the particle size and surface potential of the composite (51.00 ± 0.25nm and - 33.77 ± 2.04 mV, respectively). Further, we compared the effects of various MePEG-SSa-PCL doses (low, medium, and high) with those of free SSa, valproic acid (VPA - positive control), and saline only (model group) on acute seizure using three different acute epilepsy mouse models. We observed that compared with the model group, the three MePEG-SSa-PCL treatments showed significantly lowered seizure frequency in mice belonging to the maximum electroconvulsive model group. In the pentylenetetrazol and kainic acid (KA) acute epilepsy models, MePEG-SSa-PCL increased both clonic and convulsion latency periods and shortened convulsion duration more effectively than equivalent SSa-only doses. Furthermore, hematoxylin-eosin and Nissl staining revealed considerably less neuronal damage in the hippocampal CA3 area of KA mice in the SSa, VPA, and three MePEG-SSa-PCL groups relative to mice in the model group. Hippocampal gamma-aminobutyric acid-A (GABA-A) receptor and cleaved caspase-3 expression levels in KA mice were significantly higher and lower, respectively, in the three MePEG-SSa-PCL treatment groups than in the model group. Thus, MePEG-SSa-PCL exhibited a more potent antiepileptic effect than SSa in acute mouse epilepsy models and could alleviate neuronal damage in the hippocampus following epileptic seizures, possibly via GABA-A receptor expression upregulation.

Anticonvulsant activities of Quercus infectoria (galls) and Trewia nudiflora (seeds) in Nepalese varieties

Background and objectives: Epilepsy is defined as the heterogeneous, synchronized abnormal electrical discharge from the brain area. The numerous synthetic antiepileptic drugs currently available are ineffective to many patients and plant-derived drugs could be an alternative. The aim of this study was to evaluate anticonvulsant activities of Quercus infectoria (galls) and Trewia nudiflora (seeds) found in Nepal. Materials and methods: Anticonvulsant activity was carried out using Isoniazide-induced clonic convulsion (INH 250 mg/kg) using rat model. Onset and duration of clonic convulsion, percentage protection and death were observed. Results: T. nudiflora showed a dose dependent hindrance on the onset of clonic convulsions when compared with the control group. Treatment with higher doses of T. nudiflora (400 mg/kg) showed significant increase (p < 0.01) in latency of clonic convulsions whereas, lower dose showed significant increase (p < 0.05) in latency of clonic convulsion. The extract of T. nudiflora protected 25% of animals from convulsion at a dose 400 mg/kg. However, Q. infectoria did not display dose dependent delay on the onset of clonic convulsion, Q. infectoria (100 and 400 mg/kg) showed insignificant increases in latency of clonic convulsions. The extract of Q. infectoria protected the 25% of animals when used at a lower dose of 100 mg/kg. Positive control group treated with diazepam at a dose 4 mg/kg showed 100% protection from clonic seizures and death. Q. infectoria (100 mg/kg) T. nudiflora (400 mg/kg) and Diazepam (4 mg/kg) showed significant decrease (p<0.01) in seizure duration (s). Q. infectoria (400 mg/kg) and T. nudiflora (100 mg/kg) showed significant decrease (p < 0.05) in seizure duration compared to control group (Normal saline 10 ml/kg). Study reports the antiepileptic effects Q. infectoria and T. nudiflora. Conclusion: The methanolic extract galls of Q. infectoria and seeds of T. nudiflora showed protective effect on Isoniazide induced convulsion.

Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of Lactuca Serriola Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract.

This study aimed to assess the potential of Lactuca serriola (Asteraceae) seed n-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were evaluated for the anxiolytic potential using the hole-board, the elevated plus maze and the light/dark test. A phenobarbitone-induced sleep test was employed for the evaluation of sedative potential. Acute anticonvulsant activity was evaluated by picrotoxin and strychnine-induced convulsion models. All extracts significantly reduced the number of head dips where n-hexane extract (400 mg/kg) showed 96.34% reduction in the tendency of head dipping when compared with the control. Mice treated with extracts preferred elevated plus maze open arms and were shown to lack open arms evasion, especially n-hexane extract (400 mg/kg)-which showed 456.14%-increased the duration of open arm stay with the respective control group. By reducing sleep latency and greatly lengthening sleep duration, L. serriola enhanced the effects of barbiturate-induced sleep. A significant increase in convulsion latency and decrease in convulsions induced by picrotoxin and strychnine duration was observed in all extract-treated groups. All the extracts exhibited anti-epileptogenic potential as the seizure score in pentylenetetrazol (PTZ)-induced kindling in mice was reduced significantly. Maximum protection was afforded by chloroform extract that reduced the seizure score by 79.93% compared with the PTZ group. Chloroform executed antioxidant effect by elevating super oxide dismutase (SOD) by 126%, catalase (CAT) by 83.53%, total glutathione (tGSH) by 149%, and reducing malondialdhyde (MDA) levels by 36.49% in the brain tissues that is further consolidated by histopathological examination. Metabolic profiling of the most active chloroform extract using Gas chromatography coupled with mass showed the presence of 16 compounds. This anti-epileptic activity was further confirmed via in silico molecular modelling studies in the active site Gamma-aminobutyric acid aminotransferase (GABA-AT) where all of the tested metabolites illustrated a potent inhibitory potential towards GABA-AT with hexadecanoic acid, 15-methyl-, methyl ester followed by octadecanoic acid, methyl ester showed the best fitting. The results indicated the possible anxiolytic and anti-epileptogenic potential of the plant and further consolidated the ethnopharmacological use of L. serriola seeds.

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<0.05). The ethanolic extract significantly increased the latency of convulsion and decreased the duration of convulsion in PTZ induced model (p<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 < 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 < 0.05 – 0.01) shortened sleep latency. At 400 and 800 mg/kg, p.o., AESM prolonged (p < 0.05) total sleeping time while EESM at 800 mg/kg, p.o. significantly (p < 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.

Eslicarbazepine, but Not Lamotrigine or Ranolazine, Shows Anticonvulsant Efficacy in Carbamazepine-Resistant Rats Developed by Window-Pentylenetetrazole Kindling.

Approximately 30% of epileptic patients develop Drug-Resistant Epilepsy. Based on evidence that shows a loss of efficacy in some sodium channel blocker antiseizure drugs in epilepsy, we focus our study on assessing the anticonvulsant efficacy of different sodium channel blockers on carbamazepine (CBZ)-resistant seizures generated using the window-pentylenetetrazole (PTZ) kindling model to verify whether one of these drugs presents some anticonvulsant effect that could have potential therapeutic use. Wistar rats were treated with a subthreshold dose of PTZ (35 mg/kg) three times/week. Fully kindled rats were then treated with a single dose of CBZ (40 mg/kg i.p.) at 2, 9 and 16 days after their last kindling stimulation to obtain CBZ-resistant rats. Right after, sodium channel blockers were tested for anticonvulsant action (lamotrigine, 30 mg/kg i.p.; eslicarbazepine, 150 or 300 mg/kg i.p.; ranolazine, 10, 20 or 40 mg/kg i.p.). Behavioral parameters included severity, latency or duration of convulsions. Our data showed for the first time directly that eslicarbazepine does have an anticonvulsant effect over CBZ-resistant seizures, while lamotrigine shows drug resistance and ranolazine demonstrates severe seizure worsening. It is of potential therapeutic relevance that eslicarbazepine could be useful to control seizures resistant to common sodium channel blockers such as CBZ.

Glyphaea brevis (Spreng) Monachino (Tiliaceae) leaf fractions protect against pentylenetetrazole (PTZ)-induced convulsion in mice


 
 
 
 Purpose: To investigate the anticonvulsant effect of Glyphaea brevis leaf fractions using a pentylenetetrazole (PTZ)-induced seizure model in mice.
 Methods: Glyphaea brevis leaf methanol extract was partitioned using n-hexane and hydro-methanol (8:2). Seizure was assessed in terms of onset of myoclonic and tonic-clonic seizure, duration of seizure and frequency of seizure. The concentrations of glutathione of catalase, glutathione peroxidase, superoxide dismutase and malondialdehyde in the brain of the mice were also determined.
 Results: The administration of the different fractions of Glyphaea brevis leaf prior to induction of seizure with PTZ prolonged the latency of convulsion in mice as well as a significant (p < 0.05) decline in the intensity of convulsion was observed. In relation to the untreated mice, there was a rise in the levels of glutathione peroxidase, superoxide dismutase, and catalase in the brain, but a decrease in malondialdehyde levels.
 Conclusion: The study results show that the fractions of Glyphaea brevis leaf have anticonvulsive properties, proving that the plant’s use in folklore medicine for treating convulsion.
 
 
 

Anticonvulsant effects of Cymbopogon giganteus extracts with possible effects on fully kindled seizures and anxiety in experimental rodent model of mesio-temporal epilepsy induced by pilocarpine

Ethnopharmacological relevanceEpilepsy is a neurological disorder of the brain characterized by periodic and unpredictable occurrence of a transient behavior alteration due to the rhythmic, synchronous and disordered firing of brain neuron. Worldwide, approximately 50 million people currently live with epilepsy and close to 80% of people with epilepsy live in poor countries. However, it was noticed in many countries worldwide that people with epilepsy and their families suffer from stigma and discrimination and that situation exposes them to high psychological conditions such as depression and anxiety as well as more physical problems including bruising and fractures from injuries related to seizures. However, several plants-based products used for epilepsy and anxiety treatments in different system of folk medicine have exhibited a significant anti-epileptic and antianxiety activities using animal models with fewer side effects. Aim of the studyThe study aimed at evaluating the antiepileptic, status post-epilepticus and anxiolytic effects of Cymbopogon giganteus decoction in rat model induced by pilocarpine. Materials and methodsA total of 90 rats were partitioned into 7 groups and treated as follow: animals of groups I (normal control) and II (considered the negative control) received distilled water (10 mL/kg); while groups III, IV, V, and VI were treated with the C. giganteus extract at 34, 85, 170 and 340 mg/kg p.o, respectively; and the group VII (considered positive control) received sodium valproate at 300 mg/kg, i.p. After 40 min post-treatment, a single dose of n-methyl-scopolamine (1 mg/kg, i.p) was administered to animals of groups (II, III, IV, V, VI, VII) followed by pilocarpine (360 mg/kg, i.p). Animal of group I (normal group) received distilled water. Rats were further observed for 6 h to evaluate the severity and the duration of the acute seizures of epilepsy according to Racine scale. Anxious behavior status post-epilepticus was also assessed in the same rats used above in the Elevated Plus Maze and number of entries into the open or closed arms and the time spent on either open or closed arms of the platform were recorded. Animals were also evaluated on Open Field Test and the number of rearing, crossing, grooming, defecation and center time were registered. ResultsC. giganteus decoction significantly (P < 0.05) reduced the animal mortality, the number and duration of convulsions and effectively increased the latency of convulsions. The plant extract significantly (P < 0.05) improved GSH level and SOD activity, reduced MDA and CAT activity, increased GABA level and decreased GABA-t activity in hippocampus. The anxiety induced by pilocarpine was also significantly (P < 0.05) inhibited by the extract of the plant. ConclusionsThus, C. giganteus has demonstrated its antiepileptic and anxiolytic activities in rat model and may be used as preventive measure for patients suffering from epilepsy seizures and anxiety.

Neuropharmacological Assessment of the Hydroethanolic Leaf Extract of Calotropis procera (Ait). R. Br. (Apocynaceae) in Mice.

Background Calotropis procera has been widely used traditionally for its analgesic and anti-inflammatory effects. It is also reportedly used in ethnomedicine for mental health disorders including epilepsy even in the absence of supporting scientific data. Thus, the potential of the plant to affect neurological functions was evaluated. Methods Irwin's test was performed to determine the effect of the oral administration of the extract (30–3000 mg kg−1) on gross behaviour and physiological function. The activity meter, rotarod, pentylenetetrazol- (PTZ-) induced convulsion, pentobarbitone-induced sleep test, and the tail immersion tests were used to evaluate the spontaneous activity, neuromuscular function, convulsive threshold, sedation, and analgesic effects of the Calotropis procera extract (30–1000 mg/kg), respectively, in mice. Results Calotropis procera extract (CPE) exhibited significant (p < 0.0001) anticonvulsant and analgesic effects. There was a significant increase in withdrawal latency of the CPE-treated animals in the tail immersion test for analgesia (p < 0.0001), while latency and duration of PTZ-induced convulsions were positively modulated. Calotropis procera extract showed significant (p < 0.0001) central nervous system depressant effects in pentobarbitone-induced hypnosis at 100–1000 mg/kg and spontaneous activity test (30–1000 mg/kg). The extract also depicted impaired motor coordination at 100–1000 mg/kg dose levels. LD50 was estimated to be above 1000 mg kg−1. Conclusions Calotropis procera extract has significant central nervous system depressant and analgesic effects in mice.

Rhein attenuates PTZ‑induced epilepsy and exerts neuroprotective activity via inhibition of the TLR4-NFκB signaling pathway

BackgroundEpilepsy is a common neurological disease that cannot be well controlled by existing antiepileptic drugs. Studies have implicated oxidative stress and inflammation in the pathophysiology of epilepsy. Rhein has a comprehensive pharmacological function in reducing inflammation and can play a neuroprotective role in many neurological diseases, however little is known about its effects on epilepsy. MethodsA model of acute epilepsy in mice was established using the Pentylenetetrazol (PTZ) ignition method to evaluate the effects of Rhein on the duration and latency of convulsions, and the number and severity of seizures. Modified Neurological Severity Score (mNSS), Rotarod and open-field behavioral task tests were performed to evaluate the neuroprotective effect of Rhein. TUNEL staining was used to assess neuronal damage, and western blot, qPCR and ELISA kits were utilized to determine the expression of inflammatory signaling protein molecules and levels of inflammatory cytokines. ResultsIn this study, we demonstrate that Rhein delayed the onset of seizures, decreased their severity, and reduced the duration and frequency of seizures in PTZ-induced epileptic mice. Furthermore, we found that Rhein blocked neurological deficits induced by PTZ. In addition, our results show that Rhein inhibited the activation of the TLR4-NFκB signaling pathway and decreased the secretion of the inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-18. ConclusionOur results suggest that the anticonvulsant and neuroprotective effects of Rhein are achieved by disrupting the processes involved in PTZ acquisition of epilepsy.

Antiepileptic Effects of Cicadae Periostracum on Mice and Its Antiapoptotic Effects in H2O2-Stimulated PC12 Cells via Regulation of PI3K/Akt/Nrf2 Signaling Pathways.

Cicadae Periostracum (CPM), a commonly used animal traditional Chinese medicine (TCM), possesses antifebrile, spasmolytic, antiasthmatic, and antiphlogistic effects. In our present paper, we aimed to systemically investigate the antiepileptic effects of CPM in epileptic mice and explore the related molecular mechanism. Pentylenetetrazole- (PTZ) and strychnine-induced convulsion mice were established, and the results showed CPM could prolong the latency of convulsion and death and improve the neuronal damage in the hippocampus of PTZ-induced mice. Furthermore, the H2O2-treated PC12 cells were prepared to explore the possible mechanisms for the antiepileptic effects of CPM. CCK-8 results showed that CPM significantly improved the cell viability of H2O2-treated PC12 cells. Results of the acridine orange- (AO-) ethidium bromide (EB) staining, cell mitochondrial membrane potential (MOMP) analysis, and flow cytometry analysis showed that CPM significantly suppressed the H2O2-induced apoptosis in PC12 cells. In addition, CPM also downregulated the proapoptosis proteins, including Bax, cleaved- (C-) caspase-3, and C-caspase-9, and upregulated Bcl-2. Furthermore, CPM reduced the reactive oxygen species (ROS) levels via increasing antioxidative enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Importantly, CPM could increase the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in H2O2-induced PC12 cells and can promote the nuclear transfer of the nuclear factor E2-related factor 2 (Nrf2) and increase the expression of heme oxygenase-1 (HO-1) in the cytoplasm. In conclusion, our present study suggested CPM possessed antiepileptic effects through antiapoptosis of neuron cells via regulation of the PI3K/Akt/Nrf2 signaling pathway.

Anticonvulsant effect of Asparagus africanus Lam. root decoction on pilocarpine-induced temporal lobe epilepsy in white mice (Mus musculus Swiss)

Asparagus africanus Lam. (Asparagaceae) is a widely used plant in traditional medicine as an anti-inflammatory, antioxidant, for the treatment of nervous disorders and epilepsy. The objective of this work was to study the anticonvulsant effects of A. africanus root decoction in white mice (Mus musculus Swiss) induced by pilocarpine. The experimental induction of "status epilepticus" and the evaluation of the anticonvulsant effects of A. africanus root decoction on pilocarpine-induced clonic and tonic convulsions were carried out. Seizure severity, latency, duration and number of clonics and tonics convulsions were evaluated. Concentrations of GABA, GABA-T, TNF-α and stress markers in the brains of mice were also estimated. A. africanus decreased the duration and number of clonic and tonic convulsions which increased the latency time of onset of clonic and tonic convulsions significantly and in a dose-dependent manner. GABA increased significantly in the brains of animals treated with A. africanus and a significant decrease of GABA-T and TNF-α. A. africanus also showed antioxidant effects. These results show that A. africanus has anticonvulsant effects. A. africanus would thus contain beneficial antiradical constituents in the treatment of epilepsy. These constituents would thus oppose free radicals. These results would justify the use of this plant in traditional medicine in the treatment of epilepsy.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

Effect of valproic acid alone or combined with low dose gamma irradiation in modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway

AimThe current study evaluates the anticonvulsant effect of valproic acid (VPA) alone or combined with low dose γ-irradiation (LDR) against pentylenetetrazol-induced convulsions in rats. Material and methodsFive groups of rats were used, group I served as normal control, group II served as PTZ- control and the other three groups were pretreated with single LDR(o.5 Gy), VPA(150 mg/kg i.p.5 days) and VPA with LDR respectively before PTZ injection. Racine score, latency and duration of convulsions were assessed. Evaluation of brain neurotransmitters (glutamate and GABA) as well as AKT/m-TOR pathway (protein kinase B [AKT], mammalian target of rapamycin [m-TOR], protein S6 and caspase 3). Measurement of oxidative stress (Malondialdehyde, glutathione and nitric oxide) was carried out. Histopathological examinations of hippocampi were done. Key findingsPTZ resulted in behavioural changes (high Racine score, long seizure duration and short latency).PTZ enhanced oxidative stress state (high MDA and NO, as well as low GSH) compared to normal control. VPA alone or combined with LDR ameliorated, the convulsions and caused significant improvement in behavioural changes and other tested parameters compared to normal control. Histopathological examination of hippocampi was carried out to adjoin the biochemical changes. Certain changes were observed after PTZ injection. However, normal pictures of the other tested groups. SignificanceThe previously mentioned findings support that LDR purveyed novel anticonvulsant activity which could offer a possible contributor in the basic treatment of convulsions. This effect might be due to modulation of AkT/m-TOR pathway, reduction of oxidative stress and modulation of neurotransmitters.

Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion.

Background:The CD38/cyclic ADP-ribose (cADPR) pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion.Methods:Forty male Sprague-Dawley rats were randomly divided into five groups (n = 8 per group): sham group, ropivacaine group, ropivacaine+8-Br-cADPR (5 nmol) group, ropivacaine+8-Br-cADPR (10 nmol) group, and ropivacaine+8-Br-cADPR (20 nmol) group (no rats died). Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde (MDA) and superoxide dismutase (SOD) assays.Results:Intraperitoneal injection of ropivacaine (33.8 mg/kg) induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion (P = 0.031 and 0.020, respectively, compared with the sham group). Intraventricular injection of 8-Br-cADPR (5, 10, and 20 nmol) significantly prolonged convulsion latency (P = 0.037, 0.034, and 0.000, respectively), reduced convulsion duration (P = 0.005, 0.005, and 0.005, respectively), and reduced convulsion behavior scores (P = 0.015, 0.015, and 0.000, respectively). Intraventricular injection of 8-Br-cADPR (10 nmol) also increased the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio (P = 0.044) and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDA and SOD levels (P = 0.014, 0.044, 0.001, and 0.010, respectively) compared with the ropivacaine group.Conclusions:The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.

Phytochemical Analysis and Evaluation of Anticonvulsant Effect of Chamomile (Matricaria chamomilla L.) Flower Extract in Chicks

This study was carried out to investigate the effect of chamomile flower aqueous extract on different biochemical parameters in pentylenetetrazole (PTZ) induced-convulsive chicks. Parameters included were serum total antioxidant capacity (T-AOC), serum and brain gamma-aminobutyric acid (GABA), serum cholinesterase enzyme activity (ChE), electrolytes (Na+,K+, and Cl-), total calcium (Ca2+), serum glucose and total protein concentration.The dried flowers parts of chamomile (Matricaria chamomilla L.) were subjected to aqueous extraction and given at (200, 400 and 600mg/kg orally), for its anticonvulsant effects and the effect was compared with the standard anticonvulsant drug sodium valproate (200mg/kg). A dose of 200mg/kg showed full protection against PTZ convulsions, whereas doses of 400 and 600 mg/kg reduced the latency and onset of convulsion. The results suggest that the aqueous extract of chamomile flower may produce anticonvulsant effects via biochemical changes including significant increases in serum T-AOC, serum GABA, serum ChE activity and Na+, and a significant reduction in K+ and serum glucose concentration have been observed.

Evaluation of the sedative and hypnotic effects of astragalin isolated from Eucommia ulmoides leaves in mice

The purpose of this study was to evaluate the effects of astragalin on the central nervous system. Astragalin is a monomeric compound found in the leaves of Eucommia ulmoides using a system solvent method. In the experiments, astragalin showed significant effects on mice, including reduced spontaneous activity, increased sleep ratio, shortened sleep latency and lengthened sleep time with a subthreshold or superthreshold dose of pentobarbital sodium. In addition, astragalin effectively reduced the convulsion rate and prolonged convulsion latency. These findings confirmed that astragalin had excellent sedative and hypnotic effects and has potential to be commercialised as a novel nutraceutical agent to promote calming and improve central nervous system-associated pathologies.

Octreotide ameliorates inflammation and apoptosis in acute and kindled murine PTZ paradigms

In the present study, the role of octreotide (OCT) in pentylenetetrazole (PTZ) kindling as well as in acute convulsion models was evaluated. Mice were allocated in groups as (1) control saline; (2) acute PTZ (PTZ-a; 60mg/kg, i.p.), as a single convulsive dose; and (3) kindled (PTZ-k) receiving nine subconvulsive doses of PTZ (40mg/kg, i.p.) for 17days. Groups 4-7 received either valproic acid (VPA) 50mg/kg or OCT (50μg/kg, Sandostatin®) 30min by oral gavage before PTZ-a or PTZ-k. The median seizure stage, latency onset of first stage 4/5 seizures, and incidence of convulsing animals were recorded. Cortical dopamine (DA), tumor necrosis factor (TNF)-α, interleukin (IL)-10, caspase (Casp)-3, myeloperoxidase (MPO), and nitric oxide (NO) were assessed in addition to inducible nitric oxide synthase (iNOS) that was evaluated immunohistochemically in a different set of groups. OCT halted PTZ-induced epilepsy delaying convulsion latency via modulating MPO and TNF-α and normalizing IL-10 with both treatment regimens. In PTZ-k, it decreased Casp-3 activity, NO level, and iNOS immunoreactivity. OCT in both paradigms decreased DA concentration. The current investigation implicates a crucial role for OCT in modulating PTZ-induced kindling by regulating inflammatory and apoptotic effects.