Seizures In Epilepsy Model Research Articles

Synthesis and Evaluation of Antiepileptic Activity of Newly Designed Coumarin-Sulfonamide Hybrids

The combination of different heterocyclic rings to form a multifunctional compound is a new approach to get the potent and selective compounds, which can act as antiepileptic drugs. In this study we designed and synthesized the hybrid of the coumarin ring with sulfonamide moiety. Coumarin sulfonamide hybrids (CS1-CS7) were synthesized by Knoevenagel condensation of methyl anilinosulfonyl acetate with substituted salicyaldehyde in the presence of catalytic base. The synthesized hybrid compounds were characterized by means of mass, 1H & 13C NMR and FTIR spectroscopy, moreover antiepileptic activity was screened through seizure model of epilepsy using pentylenetetrazole and maximal electroshock. According to results, compound CS-2 remained to be highest potent and presented significant protection at 60 mg/kg in both the seizure models. Furthermore, compound CS-2 was also evaluated for biochemical and a histopathological study in which no significant results were obtained. In addition to former activities, compound CS-2 was also examined for liver toxicity.

Effect of Pre-Treatment with Acetaminophen on Hippocampal Oxidative, Inflammatory, and Apoptotic Parameters in PTZ-Induced Acute Seizure Mice Model

The current investigation aimed to determine the effects of pre-treatment of acetaminophen on seizure susceptibility and expressions of hippocampal oxidative-nitrosative stress and inflammatory markers after exposure to pentylenetetrazole administration in a mouse model. The seizure symptoms of pentylenetetrazole-treated mice were assessed using Racine classification and latency to first myoclonic jerk. Then, several parameters including TAS, TOS, NO, TNF-α, caspase-3, GABA, and glutamate levels were quantitated by commercial kits. The pre-treatment of acetaminophen significantly suppressed pentylenetetrazole-induced seizures. Also, it significantly increased the TAS and GABA values and significantly decreased the TOS, NO, TNF-α, caspase-3, and glutamate values in the hippocampus. These findings are indicative of the antiseizure potential of pre-treatment with acetaminophen in the pentylenetetrazole-induced acute seizure model of epilepsy. This effect may be due to its impact on antioxidant, anti-inflammatory, and anti-apoptotic pathways.

Evaluation of the effect of volatile oil extract of Nigella sativa seeds on maximal electroshock-induced seizures in albino rats

Background: Epilepsy is one of the most common serious neurological disorders, responsible for substantial morbidity and mortality due to the seizures and the available medications. Natural products from folk remedies have contributed significantly in the discovery of modern drugs with novel structures and better safety and efficacy profiles. In this regard, one such plant is Nigella sativa. Aims and Objectives: (i) To evaluate the anticonvulsant activity of volatile oil extract of N. sativa seeds by maximal electroshock (MES)-induced seizure model of epilepsy in albino rats; (ii) To evaluate the influence of volatile oil extract of N. sativa seeds on the anticonvulsant activity of sodium valproate in albino rats. Materials and Methods: Male Albino rats (150-200 g) were randomly selected, from Central Animal Facility, Mysore Medical College and Research Institute, Mysore. The anticonvulsant activity was screened using MES-induced seizure model. Albino rats were divided into six groups of six rats each. Six groups were treated with gum acacia 0.5 ml (control group), sodium valproate 300 mg/kg (standard group), Groups 3, 4, and 5 were administered the test drug, volatile oil extract of N. sativa seeds at doses of 200, 400, and 600 mg/kg, respectively, and Group 6 was treated with the combination of test drug, volatile oil extract of N. sativa seeds 200 mg/kg and sodium valproate 150 mg/kg. All the drugs were dissolved in gum acacia and administered intraperitoneally 30 min prior to induction of seizures. Results: The volatile oil extract of N. sativa seeds showed the anticonvulsant activity in electroshock-induced seizure model at the dose of 400 and 600 mg/kg body weight and the potentiation of anticonvulsant activity of sodium valproate. The anticonvulsant activity of volatile oil of N. sativa seeds was less when compared to sodium valproate. Conclusions: The N. sativa seeds showed the anticonvulsant activity in MES-induced seizure model of epilepsy. This study showed that volatile oil of N. sativa seeds potentiated the effect of sodium valproate.

Neonatal seizures and disruption to neurotransmitter systems

Neonatal seizures and disruption to neurotransmitter systems

Less is More: Reducing Tau Ameliorates Seizures in Epilepsy Models.

Less is More: Reducing Tau Ameliorates Seizures in Epilepsy Models.

Silencing MicroRNAs Found to Reduce Seizures in Epilepsy Model

Silencing MicroRNAs Found to Reduce Seizures in Epilepsy Model

IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures

Increasing evidence supports the involvement of immune and inflammatory processes in the etiopathogenesis of seizures. In particular, activation of innate immune mechanisms and the subsequent inflammatory responses, that are induced in the brain by infection, febrile seizures, neurotrauma, stroke are well documented conditions associated with acute symptomatic seizures and with a high risk of developing epilepsy. A decade ago, pharmacological experiments showed that elevated brain levels of the anti-inflammatory molecule IL-1 receptor antagonist reduced seizures in epilepsy models. This observation, together with the evidence of in situ induction of inflammatory mediators and their receptors in experimental and human epileptogenic brain tissue, established the proof-of-concept evidence that the activation of innate immunity and inflammation in the brain are intrinsic features of the pathologic hyperexcitable tissue. Recent breakthroughs in understanding the molecular organization of the innate immune system first in macrophages, then in the different cell types of the CNS, together with pharmacological and genetic studies in epilepsy models, showed that the activation of IL-1 receptor/Toll-like receptor (IL-1R/TLR) signaling significantly contributes to seizures. IL-1R/TLR mediated pro-excitatory actions are elicited in the brain either by mimicking bacterial or viral infections and inflammatory responses, or via the action of endogenous ligands. These ligands include proinflammatory cytokines, such as IL-1beta, or danger signals, such as HMGB1, released from activated or injured cells. The IL-1R/TLR signaling mediates rapid post-translational changes in voltage- and ligand-gated ion channels that increase excitability, and transcriptional changes in genes involved in neurotransmission and synaptic plasticity that contribute to lower seizure thresholds chronically. The anticonvulsant effects of inhibitors of the IL-1R/TLR signaling in various seizures models suggest that this system could be targeted to inhibit seizures in presently pharmaco-resistant epilepsies.

Seizures in the intrahippocampal kainic acid epilepsy model: characterization using long-term video-EEG monitoring in the rat

Intrahippocampal injection of kainic acid (KA) in rats evokes a status epilepticus (SE) and leads to spontaneous seizures. However to date, precise electroencephalographic (EEG) and clinical characterization of spontaneous seizures in this epilepsy model using long-term video-EEG monitoring has not been performed. Rats were implanted with bipolar hippocampal depth electrodes and a cannula for the injection of KA (0.4 lg /0.2 ll) in the right hippocampus. Video-EEG monitoring was used to determine habitual parameters of spontaneous seizures such as seizure frequency, severity, progression and day-night rhythms. Spontaneous seizures were detected in all rats with 13 out of 15 animals displaying seizures during the first eight weeks after SE. A considerable fraction (35%) of the spontaneous seizures did not generalize secondarily. Seizure frequency was quite variable and the majority of the KA treated animals had less than one seizure per day. A circadian rhythm was observed in all rats that showed sufficient seizures per day. This study shows that the characteristics of spontaneous seizures in the intrahippocampal KA model display many similarities to other SE models and human temporal lobe epilepsy.

No loss of hippocampal hilar somatostatinergic neurons after repeated electroconvulsive shock: A combined stereological and in situ hybridization study

Electrically induced seizures with anesthesia and muscle relaxation (ECT) is commonly used in the therapy of psychotic depression in humans. Unmodified electroshock (ECS) is used as a model for epilepsy in the rat. In several seizure models of epilepsy, in particular the dentate hilar somatostatin-containing (SSergic) neurons have been found to undergo degeneration. To assess the potential loss of SSergic hilar neurons after repeated ECS, 10 rats were given 110 ECS, one per day, 5 days a week. One day after the last ECS the rats were anesthesized, perfused, the brains cut on a vibratome and prepared for nonradioactive in situ hybridization for somatostatin along with five control rats. Like rats given 10-36 ECS in earlier studies, the ECS-treated rats displayed a markedly increased neuronal hybridization labeling when compared with control rats. The total number of dentate hilar SSergic neurons of each rat was estimated using the optical disector technique. The mean number of hilar SSergic neurons in the ECS-treated rats was 12,785, compared to 12,392 in the control rats. The total number of hilar SSergic neurons in ECS-treated versus control rats was not significantly different (Student's t test; t value = .35; p = .74). We conclude that repeated ECS treatment does not cause loss of hilar SSergic neurons.