Duration Of Convulsions Research Articles

The Effect of Carnitine Supplementation on Cardiac Function and Ketogenic Diet Effectiveness in Patients with Drug Resistant Epilepsy on Ketogenic Diet

Abstract Background Ketogenic Diet (KD) is gaining attention as a management line in childhood drug resistant epilepsy (DRE) and it is an effective line of therapy for DRE in children. KD is a strict diet consisting of minimal carbohydrate and adequate protein intake with increased fat content. Although KD is effective for epilepsy management, it is deficient in several minerals, vitamins, and trace elements, which can lead to several early and late complications. Objective To demonstrate the effect of carnitine supplementation on cardiovascular functions in patients with DRE on KD and to highlight the effect of carnitine supplementation on efficacy of KD in seizure control. Methods This study was a clinical trial (Trial Design: Parallel 1:1) which included 52 patients with DRE on KD following up at Pediatric Neurology and Clinical Nutrition Outpatient Clinics at Ain Shams University children`s Hospital (or admitted as inpatient) in the period from March 2022 to October 2022 Results There was a statistically significant decrease in the CSSS after 6 months compared to initial presentation among the L-carnitine supplemented group. After 6 months of L-carnitine supplementation, the supplemented group showed significant increase in interventricular wall thickness diameter (IVSD) and significant increase in posterior wall thickness (PWT). Left ventricular end-diastolic diameter (LVED) and left ventricular (LV) mass index showed also increased but didn’t reach significance statistically after L- carnitine supplements. There was no statistically significant difference between carotid intima-media thickness CIMT at initial presentation and after 6 months among L-carnitine supplemented group. Conclusion After six months of L-carnitine supplementation in patients with DRE on KD, there was improvement in the frequency and duration of convulsions among L-carnitine group. Regarding ECHO finding, L-carnitine group showed increase in interventricular wall thickness diameter (IVSD) and posterior wall thickness (PWT). Left ventricular end-diastolic diameter (LVED) and left ventricular (LV) mass index also showed increases but didn’t reach statistical significance after L- carnitine supplementation. There was no statistically significant difference in carotid intima-media thickness CIMT at initial presentation and after 6 months among L-carnitine supplemented group.

Formulation and Characterization of Gabapentin-Loaded Bigel For Transpinal Delivery to Brain

In this research, the focus was on the design and evaluation of novel two-phase systems known as bigels (BGs) for the transpinal (TS) drug delivery of gabapentin. BGs combine the advantages of hydrogels and organogels while mitigating the drawbacks of individual gels. The formulation involved preparing hydrogels and organogels using carbopol 940 in varying concentrations, which were later combined in a 1:1 ratio to produce BGs. The Fourier-transform infrared spectroscopy (FTIR) analysis indicated the interaction between the drug and polymer was nil. The formulated BG formulations underwent comprehensive characterization, including assessments of physical appearance, pH, viscosity, swelling index, spreadability, drug content, in-vitro release, ex-vivo permeation, skin irritation, and antiepileptic activity. Formulation B5 emerged as the optimized formulation based on various evaluation parameters. Skin irritation studies demonstrated compatibility with the skin, showing no adverse reactions. In antiepileptic activity, rats receiving gabapentin BG via the TS route exhibited a significant reduction in convulsion duration compared to control groups that received BG without the drug or free drug solution orally. Conclusively, the study suggests that the developed BGs containing gabapentin, when applied through the TS route on the back of the neck, hold promise for reaching the brain effectively. This method presents a potential avenue for enhanced drug delivery in the control of epilepsy.

Prevalence and predictors of magnesium imbalance among critically ill diarrheal children and their outcome in a developing country

Despite having essential roles in maintaining human body physiology, magnesium has gained little attention. We sought to evaluate the prevalence and predictors of magnesium imbalance in diarrheal children admitted to an intensive care unit. This retrospective data analysis was conducted among children admitted between January 2019 and December 2019. Eligible children were categorized by serum magnesium levels that were extracted from the hospital database. Among 557 participants, 29 (5.2%) had hypomagnesemia, 344 (61.8%) had normomagnesemia and 184 (33.0%) had hypermagnesemia. By multivariable multinomial logistic regression, we have identified older children (adjusted multinomial odds ratio, mOR 1.01, 95% CI: 1.004–1.018, p = 0.002) as a predictor of hypomagnesemia. Conversely, younger children (adjusted mOR 0.99, 95% CI: 0.982–0.998, p = 0.02), shorter duration of fever (adjusted mOR 0.92, 95% CI: 0.857–0.996, p = 0.04), convulsion (adjusted mOR 1.55, 95% CI: 1.005–2.380, p = 0.047), dehydration (adjusted mOR 3.27, 95% CI: 2.100–5.087, p<0.001), pneumonia (adjusted mOR 2.65, 95% CI: 1.660–4.240, p<0.001) and acute kidney injury (adjusted mOR 2.70, 95% CI: 1.735–4.200, p<0.001) as the independent predictors of hypermagnesemia. The mortality was higher among children with hypermagnesemia (adjusted mOR 2.31, 95% CI: 1.26–4.25, p = 0.007). Prompt identification and management of the magnesium imbalance among critically ill diarrheal children might have survival benefits, especially in resource-limited settings.

A COMPARATIVE STUDY OF FIRST EPISODE STATUS EPILEPTICUS AND MULTIPLE EPISODES OF STATUS EPILEPTICUS IN EMERGENCY DEPARTMENT OF TERTIARY HOSPITAL OF BUNDELKHAND REGION, CENTRAL INDIA

Objective: Status epilepticus (SE) is a medical emergency that necessitates prompt and intensive treatment to prevent damage to the brain and other complications. SE can occur in any age group, but it is most observed in infants and the elderly. The diagnosis of convulsive SE is primarily clinical, but neuroimaging and laboratory studies are required to identify the underlying cause when convulsion is subsided. Bundelkhand region is a proposed state, located between Uttar Pradesh and Madhya Pradesh in central India, has a population of approximately 18 million, with around 14 million residing in rural areas (Census 2011). This region is infamous for its backward healthcare and education systems. This study aims to compare the outcomes of individuals experiencing their first episode of SE versus those with multiple episodes in terms of seizure control or progression to refractory or super-refractory status, considering the underlying causes. Methods: A total of 100 participants were selected for the study at MLB Medical College, Jhansi, between March 2020 and November 2021. Before participation, written informed consent was obtained after explaining the study’s objectives and procedures in detail. Data were recorded on an Excel sheet and analyzed using the Statistical Package for the Social Sciences software, applying appropriate statistical tests when necessary. Results: Among the 100 patients with SE, the common etiological factors were anticonvulsant drug withdrawal (33%) and central nervous system (CNS) infections (33%), followed by metabolic encephalopathy (17%), cerebral vascular accidents (12%), and hypoxemic encephalopathy (5%). The patients were managed according to standard protocols and drug availability. The outcomes were categorized as seizure control, hospital death, or development of refractory or super-refractory status. Among the patients, 35% developed refractory SE, and within that group, 29% progressed to super-refractory status. Conclusion: The fatality rate of SE was 14.0%. Predictors of higher mortality rates included the first episode of SE, patient’s age, lack of response to initial antiepileptic drugs, duration of convulsions, and untreatable underlying causes. Etiologies such as CNS infections and anticonvulsant drug withdrawal were considered preventable and have better outcomes.

Anti-convulsant Effects of Scutellarein in a PTZ Kindling Model in Mice

Background: Epilepsy is a chronic neurological condition with various underlying mechanisms. It is known to affect a multitude of people across the globe, regardless of age and gender. Seizures associated with epilepsy involve the participation of stimulatory glutamatergic mechanisms along with inflammation and oxidative damage. Objectives: In this investigation, the anti-epileptic effect of scutellarein, a phytochemical compound isolated from Erigeron breviscapus (Vant.), has been evaluated in the pentylenetetrazol (PTZ) kindling epilepsy model in mice. Materials and Methods: The experimental mice were categorized into six groups with six animals in each. The first control group was given normal saline. The second group was provided only PTZ through an intraperitoneal route to induce seizures. The third and fourth groups received two oral doses of scutellarein (10 and 20 mg/kg) before 30 min of PTZ induction. Diazepam was intraperitoneally administered to the fifth group as a positive control. The impact of scutellarein on the duration and initiation of clonic and tonic convulsion, mortality, kindling, mobility, and immobility duration in PTZ-induced rodents was estimated. Also, the impact of scutellarein on oxidative stress markers and antioxidant and inflammatory marker levels was also evaluated. Results: Scutellarein treatment was able to reduce PTZ-induced seizures in mice. In PTZ animals, scutellarein lowered the seizure severity by suppressing the onset and duration of convulsions. Scutellarein successfully modulated the PTZ-provoked changes in gamma-aminobutyric acid (GABA), glutamate, and dopamine levels, as well as Ca2+ ATPase and Na+ K+ ATPase activity. Conclusion: Furthermore, it remarkably reduced the oxidative stress markers and decreased the contents of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in PTZ animal brain tissues, confirming its anti-convulsant potential.

In-vivo anti-epileptic study of newly synthesized pregabalin derivatives based on docking studies

ABSTRACT Objective The goal of the present study is to examine pretreatment with Schiff bases and derivatives of pregabalin along with their metal (Zn and Cu) complexes on the severity of epilepsy, latency time, duration of convulsions, seizure score and survival rate in mice. Methods To achieve the goal, a molecular docking study of analogues was carried out on a specific molecular target, such as the alpha-2δ receptor (PDB ID: 6ND9); which revealed the significant binding affinity of the analogs to their respective target. Based on the docking information, all pregabalin derivatives were synthesized and in-vivo antiepileptic effect was confirmed by applying the PTZ model that prioritized the most crucial significant points responsible for biological activity. Results The test compounds markedly increased the latency of the first seizure and reduced the frequency of seizures throughout the body and frequent spinning and jumps. Additionally, treatment with pregabalin derivatives in mice that received PTZ significantly reduced the duration of seizures and seizure score. However, it increased the survival rate of the mice. Discussion Since the newly synthesized compounds were more active as compared to the parent drug in some respects; therefore, the expansion of the project can be planned to explore clinical side of the drugs in the future.

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.

Correlation between serum zinc and brain injury in infants with mild gastroenteritis complicated with benign infantile convulsion and febrile convulsion

To investigate the association between serum zinc levels and convulsive brain injury in infants with mild gastroenteritis complicated with benign infantile seizures (BICE) and febrile seizures (FC). A case-control study method was conducted. 120 children with mild gastroenteritis and convulsion admitted to the First Affiliated Hospital of Hebei North University from January 2020 to January 2022 were enrolled as the research subjects. They were divided into BICE group and FC group according to the type of convulsion. The serum zinc level, the frequency and duration of convulsion, and the occurrence of convulsive brain injury in the two groups were recorded. Multivariate Logistic regression analysis was used to screen the risk factors for convulsive brain injury. The Spearman correlation method was used to analyze the association between serum zinc levels, clinical characteristics of convulsion and convulsive brain injury. A total of 120 children were enrolled, of which 81 developed to BICE and 39 developed to FC during hospitalization. The serum zinc level of children in the FC group was significantly lower than that in the BICE group (μmol/L: 39.24±6.50 vs. 48.65±7.21, P < 0.01). In the BICE group and FC group, the serum zinc level in children with more than 2 convulsions was significantly lower than that in the children with one convulsion (μmol/L: 37.65±6.50 vs. 53.17±7.55 in the BICE group, and 30.27±5.58 vs. 44.16±7.57 in the FC group, both P < 0.01). Serum zinc level in children with convulsion duration ≥ 5 minutes was significantly lower than that in the children with convulsion duration < 5 minutes (μmol/L: 38.75±6.74 vs. 51.21±7.58 in the BICE group, and 31.08±5.46 vs. 45.19±7.25 in the FC group, both P < 0.01). Moreover, the serum zinc level of children with different convulsion frequency and duration in the FC group was significantly lower than that in the BICE group (all P < 0.01). Among the 120 children, 9 cases of convulsive brain injury occurred, and the incidence rate was 7.50%. The incidence of convulsive brain injury in the BICE group was 1.23% (1/81), which was significantly lower than 20.51% in the FC group (8/39, P < 0.01). The serum zinc level of children with convulsive brain injury was significantly lower than that of children with non-brain injury (μmol/L: 28.50±5.00 vs. 60.22±7.31, P < 0.01), and the number of convulsion was significantly higher than that of non-cerebral injury (≥ 2 convulsions: 100.00% vs. 1.80%, P < 0.01), and the duration of convulsion in children with brain injury was significantly longer than that of non-brain-injured children (convulsion duration ≥ 5 minutes: 100.00% vs. 11.71%, P < 0.01). Multivariate Logistic regression analysis showed that decreased serum zinc level [odds ratio (OR) = 2.147, 95% confidence interval (95%CI) was 1.354-3.403], increased number of convulsion (OR = 3.452, 95%CI was 1.266-9.417), and prolonged convulsion duration (OR = 3.117, 95%CI was 1.326-7.327) were independent risk factor for convulsive brain injury in children with mild gastroenteritis and convulsion (all P < 0.05). Spearman correlation analysis showed that serum zinc level, convulsion ≥ 2 times, duration of convulsion ≥ 5 minutes and convulsion ≥ 2 times + convulsion duration ≥ 5 minutes were significantly negatively correlated with the occurrence of convulsive brain injury in FC children (r values were -0.546, -0.517, -0.522, and -0.528, all P < 0.01). There was no significant correlation between serum zinc level, convulsion ≥ 2 times, convulsion duration ≥ 5 minutes and convulsion ≥ 2 times+convulsion duration ≥ 5 minutes and convulsive brain injury in BICE children (r values were -0.281, -0.129, -0.201, -0.243, all P > 0.05). Serum zinc level is related to the characteristics of convulsive symptoms in children with mild gastroenteritis complicated with FC, and has a strong negative correlation with the occurrence of convulsive brain injury. Active targeted intervention and treatment may help reduce the incidence of brain injury in children.

A stimuli-responsive nanocarrier for diagnosis of seizures and inhibition of glutaminase in epilepsy

Epilepsy is marked by unpredictable and recurrent episodes of seizures. It is characterized by glutamate excitotoxicity and changes in stimuli such as pH, temperature and oxidative environment. This study aimed to formulate novel nanoparticulate theranostic nanocarrier for combined effects of diagnosis and treatment of epilepsy by: i) in-situ detection of epileptic conditions through characteristic changes in pH through the synthesis of pH-responsive polymer (CS-g-PD) and ii) ‘on-demand’ therapeutic alleviation of epileptic seizures through an inhibitor of glutaminase, 6-diazo-5-oxo-norleucine (DON). The formulation of DON-CS-g-PD-SLNs possessed nanodimensions (∼197.56 ± 17.87) nm and zeta potential (4.19 ± 0.29), with entrapment efficiency of (80.29 ± 0.006%). The coating pH-responsive polymer showed good sensitivity for acidic conditions by releasing the drug in pH 6.4 and resisting release in higher pH 7.2. In-vivo studies in Wistar rats showed suppression of epileptic seizures, escalation in the duration latency and reduction in duration of convulsions and recovery period. Furthermore, it was also successful in reducing the levels of glutaminase (p < 0.0001) in the brain of PTZ-kindled rats, thereby leading to a decrease in glutamate levels (p < 0.01). Hence, the nanocarriers show promising potential as ‘on-demand’ theranostics in epilepsy by reducing both the incidence and severity of convulsions.

Evaluation of anticonvulsant activity of Harpagophytum procumbens leaves (Devil’s claw) in Swiss albino mice

Abstract Introduction: The aim of this study was to examine the anticonvulsant properties of an ethanolic extract derived from the leaves of Harpagophytum procumbens (commonly known as devil’s claw) in Swiss albino mice. Materials and Methods: The ethanolic extract of H. procumbens leaves (EHPL) was administered orally at doses of 400 and 800 mg/kg body weight, and two animal models were used to assess its anticonvulsant activity: the maximal electroshock (MES) and pentylenetetrazole (PTZ) models of convulsions. The duration of tonic phase of hind limb extension and extended seizure latency period were recorded. Results: The results showed that the EHPL at a dosage of 400 mg/kg significantly reduced the duration of tonic convulsions in the hind limbs in the MES-induced seizures model, while EHPL at 800 mg/kg significantly increased the latency period of clonic convulsions in the PTZ-induced seizures model. Conclusion: These findings suggest that EHPL may be useful in managing grand mal epilepsy and absence seizures as it displayed significant antiepileptic activity in both models at 400 and 800 mg/kg p.o. The study is important as it will help to identify new sources of anticonvulsant drugs and contribute to the development of alternative treatment options for seizure disorders. The following core competencies are addressed in this article: Medical knowledge.

Neuropharmacological assessment of the methanolic stem back extract of Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) in mice

BackgroundMedicinal plants have recently attracted attention on a global scale for therapeutic interventions in the field of neuroscience. Anopyxis klaineana, a medicinal plant widely used in West Africa, has been studied extensively for its anti-inflammatory effects. However, studies on its neuropharmacological effects are quite limited. This study therefore assessed the neuropharmacological potential of the methanolic stem bark extract of Anopyxis klaineana (EAK) in murine models. Materials and methodsMice were treated orally with a methanolic stem back extract of Anopyxis klaineana (EAK) at 10, 30 or 100 mg/kg followed by testing in the elevated plus-maze (EPM) and open field (OF) tests for anxiolytic-like effects. EAK's antidepressant-like potential was also evaluated in the tail suspension test (TST), while anticonvulsant and central analgesic effects were evaluated with the pentylenetetrazol (PTZ)-induced convulsion threshold and tail withdrawal tests respectively at 30, 100 or 300 mg/kg. The extract was additionally subjected to chromatographic analyses using high resolution HPLC-MS. ResultsTotal ion current chromatogram of EAK revealed several peaks suggestive of secondary metabolites of the plant extract. EAK significantly (p<0.05) reduced depression-like behaviours in the TST although not as potent as fluoxetine (ED50: EAK=43.39±2.5; fluoxetine=1.16±1.6) (F3,20=9.663, p = 0.0004). It also showed significant anticonvulsive effect by reducing the frequency and duration of PTZ-induced convulsions (ED50=48.53±2.5 mg/kg) (F3,19=5.136, p = 0.0091). This anticonvulsant effect was seen in both clonic and tonic convulsions at 30 and 300 mg/kg. Additionally, EAK-treated mice showed higher latency to tail withdrawal in the analgesia test. We also observed significant (p<0.05) dose-dependent increase in anxiolytic-like effects in EAK-treated animals in the EPM (F3,20=10.77, p = 0.0002) and OF tests (F3,22=5.079, p = 0.008). ConclusionsThe methanolic Anopyxis klaineana stem back extract exhibits anxiolytic-like, antidepressant-like, analgesic and anticonvulsant effects in murine models for assessing neuropharmacological activity and is a good source for novel neuroactive compounds.

Evaluation of Flurbiprofen's anticonvulsant properties in pilocarpine-induced convulsions in mice

Background: Flurbiprofen is a nonsteroidal anti-inflammatory drug, it has non-selective COX inhibition properties, some NSAIDS has an anticonvulsant effect and benefit as an analgesic in seizure patient.&#x0D; Objective: we aimed to evaluate the possible anticonvulsant effect of flurbiprofen in mice.&#x0D; Methods: We used 25 mature male mice for our study, the mice were divided into five groups, then to prevent peripheral cholinergic activation, mice in all groups were injected intraperitoneally with atropine sulphate (1 mg/kg) subcutaneously one hour after dosing. Seizures were induced ten minutes later with a 300 mg/kg i.p. injection of pilocarpine. After the pilocarpine injection, the animals were monitored for 1 hour. seizures severity was tested by the Racine scale.&#x0D; Results: flurbiprofen at 0, 10, 20 and 40 mg/kg orally causes a significant decrease in the onset of convulsion and a considerable decrease in the duration of convulsion in comparison with the control group. Flurbiprofen at 20 and 40 mg/kg orally inhibited seizure scores in pilocarpine-treated mice in a dose-dependent manner. High-dose of flurbiprofen (40 mg/kg) significantly reduced seizure scores, similar to diazepam.&#x0D; Conclusion: flurbiprofen has potential anticonvulsant properties in mice models, further study must be conducted to assess the primary mechanism of action.&#x0D;

Evaluation of the anticonvulsant properties of flurbiprofen in pilocarpine-induced convulsions in mice

Background and objective: Flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), possesses non-selective COX inhibition properties. Some NSAIDs exhibit anticonvulsant effects and provide analgesic benefits for seizure patients. This study aimed to assess the potential anticonvulsant action of flurbiprofen in mice. Methods: Twenty-five mature male mice were divided into five groups for the study. To prevent peripheral cholinergic activation, mice in each group were injected intraperitoneally with atropine sulfate (1 mg/kg) subcutaneously one hour after dosing. Seizures were induced ten minutes later using an intraperitoneal injection of 300 mg/kg of pilocarpine. Following pilocarpine injection, the animals were monitored for 1 hour. Seizure severity was assessed using the Racine scale. Results: Oral administration of flurbiprofen at doses of 0, 10, 20, and 40 mg/kg resulted in a significant decrease in convulsion onset and a substantial reduction in convulsion duration compared to the control group. Flurbiprofen at 20 and 40 mg/kg inhibited seizure scores in pilocarpine-injected mice in a dose-dependent manner. A high dose of flurbiprofen (40 mg/kg) significantly reduced the duration of convulsions, delayed convulsion onset, and decreased seizure scores in mice (p &lt;0.05). Conclusions: Flurbiprofen exhibits significant dose-dependent anticonvulsant activity. Further studies are necessary to determine the primary mechanism of action.

Attenuation of Strychnine-Induced Epilepsy Employing Amaranthus viridis L. Leaves Extract in Experimental Rats.

Epilepsy is one of the most prevalent neurological illnesses defined by periodic seizures with or without loss of consciousness caused by aberrant neural activity. There are many allopathic medications available for the treatment of epilepsy such as phenytoin (PHY), but the side effects are a major concern. Therefore, the present study involved the evaluation of the pharmacological significance of Amaranthus viridis L. extract (EAV) in the management of strychnine (STR)-induced epilepsy. STR (3.5 mg/kg, i.p.) was injected into male rats 30 minutes after the pre-treatment of a standard drug (PHY: 20 mg/kg) and the two doses of EAV (EAV-200 and EAV-400 mg/kg, p.o.) to the respective groups to cause the convulsions. The anti-convulsant effect of EAV-200 and EAV-400 against STR-induced convulsion in rats was investigated in terms of convulsion onset, duration of convulsions, number of convulsions, and convulsion score. Furthermore, the mitochondrial function and integrity in the brain's prefrontal cortex (PFC) were also estimated. EAV-400 significantly increased the onset of convulsion from 61.67 ± 3.051 to 119.2 ± 2.738 and reduced the STR-induced duration of convulsions from 144.8 ± 3.582 to 69.17 ± 3.736, number of convulsions from 4.000 ± 0.1592 to 1.533 ± 0.1542, and convulsion score from 5.000 ± 0.3651 to 2.833 ± 0.3073 in rats. EAV-400 significantly attenuated the STR-induced decrease in the mitochondrial function and integrity of the rat PFC. In rats, EAV-400 significantly accelerated the onset of convulsions while decreasing the STR-induced duration, frequency, and score. Based on investigational findings, EAV-400 could be inferred to be a possible anti-epileptic option for the treatment of epilepsy of this plan in preclinical research.

The Effect of High-Dose Methyl Vitamin B12 Therapy on Epileptogenesis in Rats: An In Vivo Study.

Introduction Epileptogenesis has been considered one of the most prevalent diseases affecting significant numbers of individuals worldwide. Since vitamin B12 has been reported to possess antiepileptic effects, this supports that vitamin B12 deficiency is correlated to seizure occurrence. Hence, this study aimed to evaluate the neuroprotective effects of vitamin B12 injection on pentylenetetrazole (PTZ)-induced rats. Methods The study was performed using 40 adult female Sprague-Dawley rats (~250 g). A 45 mg/kg PTZ was intraperitoneally injected into rat models to induce seizure effects. Different groups of rat models received methyl vitamin B12 therapy at different dosages, a low dosage of 45 µg/kg and a high dosage of 85 µg/kg, at different pre-treatment periods, one day and two weeks prior to PTZ injection. A control group, which received only PTZ injection, served as a reference. The seizure latency, seizure intensity, and differences in the quality of seizures and their characteristics, from simple twitches to complete seizures, were observed after 30 minutes of PTZ injection. Results In general, the latency to convulsion significantly increased when vitamin B12 pre-treatment was employed. The longest latency time (LT) of 520.63±73.83 seconds was observed when a high dosage of vitamin B12 at 85 µg/kg was injected one day prior to PTZ inoculation, which was significantly higher than that of the control group at 176.88±62.67 seconds (P<0.001). Moreover, the duration of convulsion significantly decreased in which the lowest duration time (DT) of 7.00±4.68 seconds was observed when a high dosage of vitamin B12 at 85 µg/kg was injected two weeks prior to PTZ inoculation, which was significantly lower than that of the control group at 257.75±41.93 seconds (P<0.001). Lastly, the percentage of the population with PTZ-induced convulsion generally decreased after vitamin B12 pre-treatment in which majority showed more of simple less aggressive twitches rather than tonic-clonic seizures. Conclusion The results showed that vitamin B12 pre-treatment alleviates the seizure occurrence among PTZ-kindled rat models. These findings then suggest that vitamin B12 is a potential strategy and treatment for epilepsy and other related epileptogenesis activities.

Xanthohumol Alleviates Epileptic Seizures in Pentylenetetrazol-Induced Convulsions in Mice by Regulating Inflammation and Oxidative Stress

Background: Epilepsy is a prevalent neurobehavioral disorder, which affects more the 50 million individuals worldwide. It is characterized by neuron hyperexcitability mediated by repetitive convulsions. The current investigation was planned to study the therapeutic properties of the xanthohumol against pentylenetetrazol (PTZ)-induced convulsions in mice by regulating inflammation and oxidative stress. Methods: The 70 mg/kg of PTZ was administered (i.p.) to the mice for stimulating the epileptic seizures and 20 mg/kg of xanthohumol was pre-treated by oral route before the 30 min of PTZ administration. The mice were observed closely for 30 min after the PTZ treatment to detect the onset and duration of clonic/tonic convulsions and mortality. The status of glutamate, GABA, dopamine, Na+K+ATPase, and Ca+ATPase were quantified using respective kits. The level of MDA, NO, GSH, and SOD were detected using standard methods. The levels of inflammatory biomarkers such as COX-2, TNF-α, NF-κB, TLR-4, and IL-1β in the brain tissues were inspected using kits. The histopathological analysis was done on the brain tissues. Results: The xanthohumol significantly (p &lt; 0.05) reduced the onset and duration of convulsions, mortality, and behavioral changes in the epileptic mice. The levels of COX-2, TNF-α, NF-κB, TLR-4, and IL-1β were significantly (p &lt; 0.05) decreased in the epileptic mice by 20 mg/kg xanthohumol treatment. The levels of MDA and NO was reduced and GSH and SOD were increased by the 20 mg/kg xanthohumol treatment. The 20 mg/kg xanthohumol significantly (p &lt; 0.05) decreased the glutamate and improved the dopamine, GABA, Na+K+ATPase, and Ca+ATPase in the epileptic mice. The findings of histopathological studies revealed that 20 mg/kg xanthohumol decreased the inflammatory signs and pyknosis in the brain tissues. Conclusion: Pre-treatment with the 20 mg/kg xanthohumol ameliorates the PTZ-triggered seizures in a mice model through its antioxidant and anti-inflammatory potentials. Hence, xanthohumol can be a promising antiepileptic candidate in the future to treat epilepsy.

Oleanolic acid suppresses pentylenetetrazole-induced seizure in vivo

ABSTRACT The aim of this study was to investigate the protective effects of triterpene oleanolic acid on the brain tissue of mice with pentylenetetrazole (PTZ)-induced epileptic seizures. Male Swiss albino mice were randomly separated into five groups as the PTZ, control, and oleanolic acid (10, 30, and 100 mg/kg) groups. PTZ injection was seen to cause significant seizures compared with the control group. Oleanolic acid significantly prolonged the latency to onset of myoclonic jerks and the duration of clonic convulsions, and decreased mean seizure scores following PTZ administration. Pretreatment with oleanolic acid also led to an increase in antioxidant enzyme activity (CAT and AChE) and levels (GSH and SOD) in the brain. The data obtained from this study support oleanolic acid may have anticonvulsant potential in PTZ-induced seizures, prevent oxidative stress and protect against cognitive disturbances. These results may provide useful information for the inclusion of oleanolic acid in epilepsy treatment.

Comparing the antiepileptic effects of atorvastatin, celecoxib, ashwagandha, clove oil, and Sodium valproate on chemo-shock induced seizures in male Wistar albino rats

Background: Antiepileptic potential of statins, COX inhibitors and other herbal medications are to be evaluated in experimental animals so that the most efficacious can be translated for human use as an adjunct to the commonly used anti-epileptic drugs. Methods: This experimental animal study grouped 30 male Wistar albino rats into 6 groups with each containing 5 rats of which one group was control, one was the standard drug and the other 4 were treatment groups which received Atorvastatin, Celecoxib, Ashwagandha and Clove oil. These drugs were administered 30 minutes prior to administering Pentylene-tetrazole which induced convulsions and the various seizure parameters were analysed. The blood samples of the animals were also assessed for anti-oxidant activity by measuring superoxide dismutase and catalase levels in the blood. Results: The onset of seizure was significantly delayed by Ashwagandha (2.55±0.94), similar to the latency shown by the standard drug (2.09±1.21). The duration of convulsions was very significantly reduced in all the 5 drug groups in comparison to the control (p&lt;0.001). The clonic jerk duration was not reduced as effectively as the standard drug. The duration of recovery time amongst the various groups was also significant (p&lt;0.05). The SOD and Catalase levels of no groups showed any possible association between the anti-epileptic efficacy of these drugs and the anti-oxidant enzyme levels. Conclusions: Ashwagandha has good anti-epileptic efficacy not less than the standard drug when the various drug groups were compared.

Exploring the Anticonvulsant Activity of Aqueous Extracts of Ficus benjamina L. Figs in Experimentally Induced Convulsions

Background. Ficus benjamina L. is an evergreen tree, native to Southeast Asia, and often known as a weeping fig. Its latex and fruit extracts are used by indigenous cultures to cure skin conditions, inflammation, vomiting, leprosy, malaria, and nasal ailments. The aqueous extract of the figs of Ficus benjamina L. has various therapeutic values, including biological activities on the central nervous system. Materials and Methods. The extract of the dried figs of Ficus benjamina L. (FBE) was prepared by defatting with petroleum ether for 16 h followed by soxhelation with 70% methanol (1 : 10 w/v) for 24 h, and standardization of the extract was carried out using HPLC with 5-HT as a standard. Electroconvulsions were induced by the maximal electroshock model, and chemoconvulsions were induced by picrotoxin. Results. The HPLC chromatogram of the Ficus benjamina L. extract showed an absorption peak with a retention time of 1.797 min, similar to that observed with standard serotonin (5-HT) solution. In the maximal electroshock model, FBE significantly reduced the duration of the tonic hind limb extensor and extensor-to-flexor ratio (E/F ratio) in a dose-dependent manner. Moreover, in the picrotoxin-induced seizure model, FBE increased the seizure latency and decreased the duration of tonic-clonic convulsions dose-dependently. We confirmed the anticonvulsant activity of the FBE extract as it attenuated both maximal electroshock and picrotoxin-induced convulsions. Conclusion. The in vivo studies revealed that the Ficus extract was found to protect the animals in electroshock-induced and picrotoxin-induced convulsions.

Evaluation of the Anticonvulsant and Antidepressant Effects of the Aqueous Extract of the Leaves of Ascotheca paucinervia (T. Anderson ex C.B. Clarke) Heine in Mice

The present study was undertaken to evaluate the anticonvulsant and antidepressant effects of Ascotheca paucinervia leaves on mice by using strychnine at 2.5mg/kg to induce convulsions and the forced swimming test to create a stressful situation, respectively. Concerning convulsions, only the 500mg/kg extract significantly increases (p&lt;0.001) the time to onset of convulsions and it non-significantly reduces the duration of convulsions induced by strychnine. In addition, the extract reduces very significantly in a dose-dependent manner the time of immobility and it significantly increases the swimming time as well as the climbing time at both doses. At the same time, the estimation of the acute toxicity of the extract from the leaves of Ascotheca paucinervia according to guideline No. 425 of the OECD (2022) shows that the latter is weakly toxic and its LD50 is greater than 5000mg/kg. In addition, the evaluation of the sedative effect of this extract shows that it produces a dose-dependent sedative effects and at doses of 250m/kg and 500mg/kg, the extract significantly potentiates the sleep induced by phenobarbital. In summary, the results obtained suggest that Ascotheca paucineervia leaves extract possesses anticonvulsant and antidepressant effects.