Anticonvulsant Effects Research Articles

The Potential of Cannabichromene (CBC) as a Therapeutic Agent.

There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa The two most abundant cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). Although the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials. In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC. SIGNIFICANCE STATEMENT: Cannabichromene (CBC) has been suggested to have disparate therapeutic benefits such as anti-inflammatory, anticonvulsant, antibacterial, and antinociceptive effects. Most of the focus on the medical benefits of cannabinoids has been focused on Δ9-tetrahydrocannabinol and cannabidiol. The preliminary studies on CBC indicate that this phytocannabinoid may have unique therapeutic potential that warrants further investigation. Following easier access to hemp, CBC products are commercially available over-the-counter and are being widely utilized with little or no evidence of their safety or efficacy.

α-Linolenic acid ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures via down-regulating JAK2/STAT3 pathway.

Epilepsy ranks fourth among neurological diseases, featuring spontaneous seizures and behavioural and cognitive impairments. Although anti-epileptic drugs are currently available clinically, 30 % of epilepsy patients are still ineffective in treatment and 52 % of patients experience serious adverse reactions. In this work, the neuroprotective effect of α-linolenic acid (ALA, a nutrient) in mice and its potential molecular mechanisms exposed to pentylenetetrazol (PTZ) was assessed. The mice were injected with pentetrazol 37 mg/kg, and ALA was intra-gastrically administered for 40 d. The treatment with ALA significantly reduced the overall frequency of epileptic seizures and improved the behaviour impairment and cognitive disorder caused by pentetrazol toxicity. In addition, ALA can not only reduce the apoptosis rate of brain neurons in epileptic mice but also significantly reduce the content of brain inflammatory factors (IL-6, IL-1 and TNF-α). Furthermore, we predicted that the possible targets of ALA in the treatment of epilepsy were JAK2 and STAT3 through molecular docking. Finally, through molecular docking and western blot studies, we revealed that the potential mechanism of ALA ameliorates PTZ-induced neuron apoptosis and neurological impairment in mice with seizures by down-regulating the JAK2/STAT3 pathway. This study aimed to investigate the anti-epileptic and neuroprotective effects of ALA, as well as explore its potential mechanisms, through the construction of a chronic ignition mouse model via intraperitoneal PTZ injection. The findings of this research provide crucial scientific support for subsequent clinical application studies in this field.

Inhibitory influence of agmatine on catamenial-like seizure susceptibility in progesterone withdrawn female rats

Catamenial epilepsy is a condition marked by an increased occurrence of seizures that coincide with the menstrual cycle in women. Our study explored the role of neurotransmitter/neuromodulator agmatine in progesterone withdrawal induced increased seizure susceptibility that is one of the causes of catamenial epilepsy. Additionally, it investigates potential interactions between agmatine and the central neurosteroid system. The experiments involved the use of female Sprague-Dawley rats. To mime the seizure susceptibility as seen in catamenial epilepsy, rats were treated with PMSG and b-HCG which cause a higher release of progesterone and later injected with Finasteride on the 11th day of post-human chorionic gonadotropin administration to cause a sudden drop of progesterone. On the 12th day, seizure susceptibility was assessed through a low-dose (35 mg/kg) pentylenetetrazol (PTZ) injection. The results revealed that agmatine treatment showed a protective effect against seizures. Furthermore, this study explored the impact of neurosteroids such as allopregnanolone or progesterone (a precursor of allopregnanolone) and neurosteroidogenic drugs like FGIN 1–27 or metyrapone (an 11β-hydroxylase inhibitor) on the anticonvulsant effect of agmatine. The findings indicated that prior administration of these substances significantly enhanced the anticonvulsant effect of agmatine. In contrast, inhibiting neurosteroid production with drugs like trilostane (a 3β-hydroxysteroid dehydrogenase inhibitor) or indomethacin (a 3α-hydroxysteroid dehydrogenase inhibitor) completely nullified agmatine's effect. Seizures were associated with elevated progesterone levels and reduced allopregnanolone levels, which were normalized by agmatine treatment. Notably, agmatine exhibited seizure protection even in ovariectomized rats, affirming the involvement of neurosteroids in its anti-seizure effects in progesterone withdrawal increased seizure susceptibility. In conclusion, these findings emphasize central neurosteroid involvement in agmatine's pharmacological effects against seizure susceptibility in progesterone withdrawal in female rats.

Assessing the Effectiveness of Eslicarbazepine Acetate in Reducing Audiogenic Reflex Seizures in the GASH/Sal Model of Epilepsy.

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug indicated as monotherapy for adults with newly diagnosed epilepsy and as adjunctive therapy for the treatment of partial seizures. Our aim was to assess the effectiveness and safety of both acute and repeated ESL administration against reflex audiogenic seizures, as shown by the Genetic Audiogenic Seizures Hamster from Salamanca (GASH/Sal). Animals were subject to the intraperitoneal administration of ESL, applying doses of 100, 150 and 200 mg/kg for the acute study, whereas a daily dose of 100 mg/kg was selected for the subchronic study, which lasted 14 days. In both studies, the anticonvulsant effect of the therapy was evaluated using neuroethological methods. To assess the safety of the treatment, behavioral tests were performed, hematological and biochemical liver profiles were obtained, and body weight was monitored. In addition, the ESL levels in blood were measured after the acute administration of a 200 mg/kg dose. Treatment with ESL caused a reduction in seizure severity. No statistically significant differences were detected between the selected doses or between the acute or repeated administration of the drug. To summarize, the intraperitoneal administration of ESL is safe and shows an anticonvulsant effect in the GASH/Sal.

An insight for the inhibition of anxiolytic and anti-convulsant effects in zebrafish using the curcumins via exploring molecular docking and molecular dynamics simulations.

In the contemporary landscape, anxiety and seizures stand as major areas of concern, prompting researchers to explore potential drugs against them. While numerous drugs have shown the potential to treat these two neurological conditions, certain adverse effects emphasize the need for development of safer alternatives. This study seeks to employ an in silico approach to evaluate natural compounds, particularly curcumins, as potential inhibitors of GABA-AT to mitigate anxiety and seizures. The proposed methodology includes generating a compound library, minimizing energy, conducting molecular docking using AutoDock, molecular dynamics simulations using Amber, and MM-GBSA calculations. Remarkably, CMPD50 and CMPD88 exhibited promising binding affinities of - 9.0kcal/mol and - 9.1kcal/mol with chains A and C of GABA-AT, respectively. Further, MM-GBSA calculations revealed binding free energies of - 10.88kcal/mol and - 10.72kcal/mol in CMPD50 and CMPD88, respectively. ADME analysis showed that these compounds contain drug-likeness properties and might be considered as potential drug candidates. The findings from this study will have practical applications in the field of drug discovery for the development of safer and effective drugs for treatment of anxiety and seizures. Overall, this study will lay the groundwork for providing valuable insights into the potential therapeutic effects of curcumins in alleviating anxiety and seizures, establishing a computational framework for future experimental validation.

Differential toxic and antiepileptic features of Vigabatrin raceme and its enantiomers

BackgroundThe study aimed to investigate the potential pharmacological and toxicological differences between Vigabatrin (VGB) and its enantiomers S-VGB and R-VGB. The researchers focused on the toxic effects and antiepileptic activity of these compounds in a rat model. MethodsThe epileptic rat model was established by intraperitoneal injection of kainic acid, and the antiepileptic activity of VGB, S-VGB, and VGB was observed, focusing on the improvements in seizure latency, seizure frequency and sensory, motor, learning and memory deficits in epileptic rats, as well as the hippocampal expression of key molecular associated with synaptic plasticity and the Wnt/β-catenin/GSK 3β signaling pathway. The acute toxic test was carried out and the LD50 was calculated, and tretinal damages in epileptic rats were also evaluated. ResultThe results showed that S-VGB exhibited stronger antiepileptic and neuroprotective effects with lower toxicity compared to VGB raceme. These findings suggest that S-VGB and VGB may modulate neuronal damage, glial cell activation, and synaptic plasticity related to epilepsy through the Wnt/β-catenin/GSK 3β signaling pathway. The study provides valuable insights into the potential differential effects of VGB enantiomers, highlighting the potential of S-VGB as an antiepileptic drug with reduced side effects. ConclusionS-VGB has the highest antiepileptic effect and lowest toxicity compared to VGB and R-VGB.

Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases.

Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases.

Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway

Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP.Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated.The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.

Theoretical calculations and molecular modelling of isoindoline compounds as anticonvulsant agents

The lack of safe and effective antiepileptic drugs is a persistent issue that could be addressed through the repurposing or further development of commonly available drugs. Due to high accuracy, low effort, and high cost, it is best to begin the search for alternative treatments with a theoretical chemical study. Isoindoline derivatives, their ΔG, and their molecular docking were subjected to the molecular level theory. Having a ΔG of -4.9, compound A1 demonstrated a unique activity against protein 1OHV (4-aminobutyrate-aminotransferase; from pig), while the same compound demonstrated distinct activity against protein 3F8E (coumarins as suicide carbonic anhydrase inhibitors) with a ΔG of -4.533. Moreover, compound A3 exhibited a unique activity against protein 6KZP (calcium channel-ligand) with a ΔG of -7.597. The undertaken DFT analysis determined the highest occupied molecular orbital (HOMO), the least unoc¬cupied molecular orbital (LUMO), and the HOMO-LUMO gap values for the studied derivatives (compound A1: -0.202, -0.091, and -0.111 eV; compound A3: -0.228, -0.102, and -0.126 eV, respectively). The ionization potential, the soft¬ness, the hardness, and other chemical properties of these compounds were subsequently computed. Drug likeness predictions were employed in order to show that the compounds adhered to Lipinski’s rule. Our results indicate that the molecular mass, log P, as well as the hydrogen bonding donors and acceptors of the herein assessed isoindoline compounds fall within acceptable ranges.

Anticonvulsant effects of Paeonia daurica subsp. macrophylla root extracts in pentylenetetrazol-induced seizure models in mice

IntroductionIn the present study, anticonvulsant effects of aqueous extract (AE), hydro-alcoholic crude extract (HE), and its fractions (F-CHCl3, F-EtOAc, F-MeOH) of Paeonia daurica subsp. macrophylla (P. daurica ssp. macrophylla) root examined by using a pentylenetetrazol-induced model (PTZ) on mice. MethodsHE and its fractions as well as AE, in concentrations of (100, 200 and 400mg/kg), valproate (Val) (100 and 200mg/kg), and saline (negative control) (10mg/kg) were injected intraperitoneally (i.p.) 30min before PTZ (80mg/kg, i.p.). The time taken before the onset of myoclonic convulsions (MC), MC duration, time taken before the onset of generalized tonic-clonic seizures (GTCS), the duration of GTCS, and the percentage of GTCS and mortality protection recorded. The plant's anticonvulsant mechanisms were assessed using flumazenil (5mg/kg, i.p.) before AE (100, 200, and 400mg/kg, i.p.) injection. GraphPad Prism software was used to compare the differences between various treatment groups with one-way analysis of variance (ANOVA) followed by Tukey–Krammer multiple comparison tests. ResultsAll the plant samples except F-EtOAc significantly delayed the onset and decreased the duration of PTZ-induced MCS and GTCS, and significantly reduced the GTCS and mortality rate. Pretreatment with flumazenil diminished the significant anticonvulsant effects of AE against PTZ-induced seizures. ConclusionsIt can report that extract of P. daurica ssp. macrophylla might be a helpful guide for future studies in the treatment of epilepsy.

Effect of Mobile Health Applications on Improving Self-Management Knowledge and Seizure Control in Epilepsy Patients: A Scoping Review.

Mobile health app-based interventions are increasingly being developed to support chronic disease management, particularly for epilepsy patients. These interventions focus on managing stress, monitoring drug side effects, providing education, and promoting adherence to medication regimens. Therefore, this scoping review aims to assess how mobile health applications improve epilepsy patients' knowledge and seizure control, and to identify the features of these apps that are frequently used and have proven to be beneficial. This scoping review was conducted using scientific databases such as ScienceDirect, PubMed, and Google Scholar, adhering to the Joanna Briggs Institute guidelines. The review framework consisted of five steps: identifying research questions, finding relevant articles, selecting articles, presenting data, and compiling the results. The literature search included all original articles published in English from 2013 to 2023. Among six articles that discussed mobile applications for epilepsy patients, all featured similar functionalities, including education on epilepsy management and seizure monitoring. Four of the articles highlighted behavioral interventions, such as reminder systems, designed to improve medication adherence. The remaining two articles focused on a side-effect reporting system that enabled doctors or health workers to evaluate and regularly monitor adverse effects. This scoping review reveals that mobile health applications employing a combination of educational and behavioral interventions for epilepsy patients significantly improve knowledge about patient self-management and medication adherence. These interventions can prevent seizures, increase awareness, enable better activity planning, improve safety, and reduce the frequency of seizures and side effects of antiepileptic drugs.

Chemical profiling, anticonvulsant and anxiolytic effects of the smoke constituents isolated from Leonotis leonurus (L.) R.Br.

Ethnopharmacological relevanceThe use of medicinal plants for central nervous system (CNS)-related ailments, such as epilepsy and anxiety, is prevalent in South Africa. Plants from the Lamiaceae family are commonly used for their therapeutic benefits. Leonotis leonurus (L.) R.Br. has been reported in ethnobotanical literature to have anticonvulsant and anxiolytic effects through the inhalation of pyrolysis products obtained by combustion of the aerial parts. Aim and objectivesTo explore the chemical profiles and CNS activity of the smoke extract and isolated constituents of L. leonurus in zebrafish larvae, through anticonvulsive and anxiolytic activity assays. Materials and methodsThe smoke extract of L. leonurus was obtained through the combustion of the aerial parts of the plant using a custom-built smoke recovery apparatus. The chemical profile of the smoke constituents was determined using Ultra-Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS). Targeted compounds were subjected to preparative High-Performance Liquid Chromatography for separation before structure elucidation using Nuclear Magnetic Resonance (NMR). The maximum tolerated concentrations, as well as the anxiolytic activity of the smoke extract were determined in five days post fertilisation zebrafish larvae. Reverse-thigmotaxis and locomotor activity of larvae in the light/dark transition assay were used to determine anxiolytic activity. Zebrafish larvae at six days post fertilisation (dpf) were subjected to several concentrations of the smoke constituents of L. leonurus. The baseline locomotor activity of the larvae was tracked for 30 min, prior to addition of pentylenetetrazole (PTZ) to induce seizure-like behaviour in the larvae, after which the locomotor activity of the larvae was once again tracked for an additional 30 min. ResultsThe UPLC-MS profiles of the smoke extract revealed the presence of two main compounds, leoleorin A and leoleorin B, which were targeted and isolated. Upon subjection to NMR spectroscopy for structure elucidation, the compounds were confirmed to be labdane diterpenoids. Both leoleorin A and leoleorin B, and the smoke extract displayed suppression of the PTZ induced seizure-like behaviour in zebrafish larvae. Under light and dark conditions, the smoke extract and compounds displayed potential anxiolytic activity at different concentrations. ConclusionOur results suggest that the smoke constituents of L. leonurus may exert anticonvulsant and anxiolytic effects which align with the traditional indications and the mode of administration.

Piroxicam reduced the intensity of epileptic seizures in a kindling seizure model

ABSTRACT Introduction: The close relationship between inflammatory processes and epileptic seizures is already known, although the exact pathophysiological mechanism is unclear. In this study, the anticonvulsant capacity of piroxicam, an anti-inflammatory drug, was evaluated. A rat pentylenetetrazole kindling model was used. Methods: Male Wistar rats, 8–9 weeks old, received piroxicam (0.15 and 0.30 mg/kg), diazepam (2 mg/kg) or saline for 14 days, and PTZ, on alternate days. Intraperitoneal was chosen as the route of administration. The intensity of epileptic seizures was assessed using a modified Racine scale. The open field test and object recognition analysis were performed at the beginning of the study to ensure the safety of the drugs used. At the end of the protocol, the animals were euthanized to measure the levels of inflammatory (TNF-a and IL-6) and anti-inflammatory (IL-10) cytokines in the cortex, hippocampus, and serum. Results:There were no changes in the open field test and object recognition analysis. Piroxicam was found to decrease Racine scale scores at both concentrations. The reported values for IL-6 levels remained steady in all structures, whereas the TNF-alpha level in the cortex was higher in animals treated with piroxicam than in the saline and diazepam subjects. Finally, animals treated with the anti-inflammatory drug presented reduced IL-10 levels in the cortex and hippocampus. onclusions: Using inflammation as a guiding principle, the anticonvulsant effect of PIRO could be associated with the hippocampal circuits, since this structure showed no increase in inflammatory cytokines.

A preclinical study to determine the anti-epileptic effect of biotin on maximal electroshock (MES) and pentylenetetrazole (PTZ) models in albino rats.

Vitamin B7(biotin) is not synthesized in our body and is retrieved from some food products like eggs, liver, pork and leafy vegetables and as well as microbes of gut. Deficiency of biotin majorly leads to loss of hair, rashes over skin, lethargy and seizures. It is noted that biotin is an anti-oxidant and negates free radical effects. Biotin is also involved in carbon dioxide metabolism and it might alter seizure threshold. Studies also suggest its effect on lipid metabolism as well. So, the primary objective of this study was to assess the efficacy of biotin in maximal electric shock (MES) induced generalized tonic-clonic seizures (GTCS) and pentylenetetrazole (PTZ) induced absence seizures. The secondary objective is to study the effect of combined treatment of biotin and sodium valproate on seizures as well as plasma lipid profile in rats. In our study 30 albino Wistar rats each were used in MES and PTZ model respectively. 30 rats were divided equally into following groups: I- distilled water (negative control) II- distilled water (positive control) III- sodium valproate (300 mg/kg) IV- biotin (10 mg/kg/day) V- biotin (10 mg/kg)+sodium valproate (150 mg/kg). We observed that the tonic hind limb extension was significantly reduced in the treatment group in MES model. Nitric oxide levels were also seen raised in combination group in MES model and all the treated groups in PTZ model. Biotin treated group showed increased high-density lipoproteins and reduced low density lipoproteins and triglycerides. Biotin had an additive effect to sodium valproate in both the models of epilepsy in rats. Further, it was also able to counteract hyperlipidemia cause by sodium valproate.

Antiepileptic effects of Allium schoenoprasum L. in the acute epilepsy model in rats

Antiepileptic effects of Allium schoenoprasum L. in the acute epilepsy model in rats

Analysis of mechanism of core points in acupuncture and moxibustion treatment for epilepsy based on data mining.

To explore the mechanism of core points in acupuncture and moxibustion treatment for epilepsy by using data mining technique, so as to provide a reference for clinical practice and experimental research. The data comes from relevant documents collected from CNKI, Wanfang, SinoMed, VIP, PubMed, Embase, Cochrane Library, EBSCO, Web of Science databases. The selected acupoints were analyzed in descriptive statistics, high-frequency acupoints group and core acupoint prescription. Further, potential target mining, "core acupoint prescription-target-epilepsy" network construction, protein-protein interactions (PPI) network establishment and core target extraction, gene ontology (GO) and KEGG gene enrichment analysis of the core acupoint prescription were carried out to predict its anti-epileptic potential mechanism. A total of 122 acupoint prescriptions were included. The core acupoint prescriptions were Baihui (GV20), Hegu (LI4), Neiguan (PC6), Shuigou (GV26) and Taichong (LR3). 277 potential targets were identified, among which 134 were shared with epilepsy. The core targets were extracted by PPI network topology analysis, including signal transducer and activator of transcription 3, tumor necrosis factor (TNF), interleukin (IL)-6, protein kinase B1, c-Jun N-terminal kinase, brain-derived neurotrophic factor, tumor protein 53, vascular endothelial growth factor A, Caspase-3, epidermal growth factor receptor, etc. The main anti-epileptic pathways of the core acupoints were predicted by KEGG enrichment, including lipid and atherosclerosis, neurodegeneration, phosphatidylinositol-3-kinase/protein B kinase signaling pathway, mitogen-activated protein kinase signaling pathway, cyclic adenosine monophosphate signaling pathway, TNF signaling pathway, IL-17 signaling pathway, hypoxia-inducible factor-1 signaling pathway, apoptosis, etc., involving neuronal death, synaptic plasticity, oxidative stress, inflammation and other related biological process. The core acupoint prescription of acupuncture and moxibustion intervention for epilepsy can act on multiple targets and multiple pathways to exert anti-epileptic effects, which can provide a theoretical basis for further clinical application and mechanism research.

Heparin-Modified Superparamagnetic Iron Oxide Nanoparticles Suppress Lithium Chloride/Pilocarpine-Induced Temporal Lobe Epilepsy in Rats through Attenuation of Inflammation and Oxidative Stress.

The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood-brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1β, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.

The potential role of nitric oxide in the anticonvulsant effects of betulin in pentylenetetrazole (PTZ)-induced seizures in mice

Epilepsy poses a significant challenge, especially for drug-resistant cases, necessitating novel treatment avenues. This study explores the potential interplay between nitric oxide (NO) and the anticonvulsant effects of betulin, a triterpene with promising neuroprotective properties. While betulin exhibits anticonvulsant effects, the specific involvement of NO remains inadequately understood, constituting a pivotal gap in current knowledge. One hundred NMRI mice were randomly assigned to diverse treatment groups, with seizures induced by pentylenetetrazol (PTZ). Parameters such as seizure threshold, nitrite levels, total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and iNOS/nNOS gene expressions were assessed. Betulin significantly increased seizure thresholds and mitigated PTZ-induced NO levels. These findings suggest a potential modulation of NO-related pathways, emphasizing betulin's anti-inflammatory and antioxidant attributes. The study sheds light on betulin's multifaceted impact on oxidative stress, NO regulation, and iNOS/nNOS gene expressions. The ability of betulin to suppress iNOS/nNOS gene expressions, leading to reduce NO production, underscores its potential as an anticonvulsant.

Investing the anti epileptic effect of Aqueous extract of Artemisia absinthium on seizures induced by pentylenetetrazole in male rats

Introduction:Epilepsy is one of the most common neurological disorders that affect social, economic, and biological aspects of human life. Thus, this study aimed to investigate the effect of Aqueous extract of Artemisia absinthium on PTZ-induced seizures in male rats. Methods: 30 male rats have been chosen randomly and divided into 5 groups; including a control group, vehicle group, and three experimental groups. Treated rats received an aqueous extract of Artemisia absinthium via i.p. injection at doses of 50, 100, and 200 mg/kg before injection of pentylenetetrazole (PTZ). Thirty minutes after injection with different doses of the herb or distilled water (vehicle group), pentylenetetrazole (PTZ; 80mg/kg) was injected intraperitoneally. Animals were immediately transferred to a special cage and the seizure behaviors were recorded by a camera for 30 minutes. Then latency time of seizure onset, stage 5 seizure duration, and incidence and rate of mortality were measured in the groups. The data analysis was carried out via one-way ANOVA and Tukey post-hoc tests. Moreover, a difference of less than<0.05 was considered significant. Results:Our results showed a significant increase in latency to reach stages 4 (P˂0.01) and 5 (P˂0.001)of tonic-clonic seizure at a dose of 100 mg/kg hyssop extract and decreased stage 5 duration (P˂0.05) and rate of mortality. Conclusion:Intraperitoneally injection of the aqueous extract of Artemisia absinthium has anticonvulsant effects on PTZ-induced seizure in a dose-response manner. Therefore, complementary research is recommended to identify some effective components of this plant on seizures.

High-definition transcranial direct current stimulation desynchronizes refractory status epilepticus

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 ​Hz (“gamma”) and lesser power in frequency bands lower than 30 ​Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time. During hd-tDCS, median relative power change over the EEG electrode chains in which power changes were maximal was +4.84%, −5.25%, −1.88%, −1.94%, and +4.99% for respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +4.13%, −5.44%, −1.81%, −3.23%, and +5.41% in the referential Laplacian montage (p ​= ​0.0012). After hd-tDCS, median relative power changes reversed over the EEG electrode chains in which power changes were maximal: −2.74%, +4.20%, +1.74%, +1.75%, and −4.68% for the respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +1.59%, +5.07%, +1.74%, +2.40%, and −5.12% in the referential Laplacian montage (p ​= ​0.0004). These findings are consistent with EEG desynchronization through theta-alpha-beta-gamma bands during hd-tDCS, helping account for the efficacy of hd-tDCS as an emerging novel anti-epileptic therapy against RSE.