Pentylenetetrazole-induced Seizures Research Articles

GluN2D subunit-containing NMDA receptors regulate reticular thalamic neuron function and seizure susceptibility

Thalamic regulation of cortical function is important for several behavioral aspects including attention and sensorimotor control. This region has also been studied for its involvement in seizure activity. Among the NMDA receptor subunits GluN2C and GluN2D are particularly enriched in several thalamic nuclei including nucleus reticularis of the thalamus (nRT). We have previously found that GluN2C deletion does not have a strong influence on the basal excitability and burst firing characteristics of reticular thalamus neurons. Here we find that GluN2D ablation leads to reduced depolarization-induced spike frequency and reduced hyperpolarization-induced rebound burst firing in nRT neurons. Furthermore, reduced inhibitory neurotransmission was observed in the ventrobasal thalamus (VB). A model with preferential downregulation of GluN2D from parvalbumin (PV)-positive neurons was generated. Conditional deletion of GluN2D from PV neurons led to a decrease in excitability and burst firing. In addition, reduced excitability and burst firing was observed in the VB neurons together with reduced inhibitory neurotransmission. Finally, young mice with GluN2D downregulation in PV neurons showed significant resistance to pentylenetetrazol-induced seizure and differences in sensitivity to isoflurane anesthesia but were normal in other behaviors. Conditional deletion of GluN2D from PV neurons also affected expression of other GluN2 subunits and GABA receptor in the nRT. Together, these results identify a unique role of GluN2D-containing receptors in the regulation of thalamic circuitry and seizure susceptibility which is relevant to mutations in GRIN2D gene found to be associated with pediatric epilepsy.

Effects of Cabergoline and Levetiracetam on the Histological and Stereological Structure of the Cerebral Cortex, Hippocampus and Cerebellum of Rats With Pentylenetetrazol-Induced Seizure

Background: Epilepcy is a chronic neurological disease, and due to its complex mechanism, the current therapeutic drugs for it are not effective enough. It may have a non-neurological origin such as astrocytes and microglia. Objective This study aims to investigate the effect of cabergoline and levetiracetam (alone or combined) on the histological and stereological structure of the cerebral cortex, hippocampus, and cerebellum in rats with pentylenetetrazol (PTZ)-induced seizure. Methods: In this experimental study, samples were 30 female rats in five groups of control, seizure (PTZ-induced kindling), seizure+levetiracetam, seizure+cabergoline, seizure+levetiracetam+cabergoline. Levetiracetam and cabergoline were used at 50 and 0.05 mg/kg doses, respectively, and half of these doses were used in the seizure+levetiracetam+cabergoline group. After anesthesia, animals’ brain tissue was removed and after preparing tissue slices, the number of neurons and neuroglia was examined using stereology technique. Results: In the cerebral cortex and in the molecular and granular layers of the cerebellum, the numbers of neurons and neuroglia in the treatment groups were not significantly different from those in the control group, but a significant decrease was observed in the CA1, CA2, and CA3 regions of the hippocampus in the seizure group compared to the control group. In dentate gyrus, the number of neurons in all treatment groups and the number of neuroglia in the seizure group showed a significant decrease compared to the control group. In the Purkinje layer of the cerebellum, there was no significant change in the number of neurons compared to that in the control group. Conclusion: The hippocampus is more involved in the occurrence of seizure activity than other parts of the brain. Neurons and neuroglia play an essential role in seizures, but more studies are needed for determining the relationship between the number of these cells and the use of cabergoline because their number decreases in different parts of the hippocampus following chronic seizures, where the relationship is different between dendrite gyrus and CA regions.

Synthesis Anticonvulsant and Cytotoxic Evaluation of Benzimidazole-Quinoline Hybrids Schiff Base Analogs

Both, benzimidazole and quinoline pharmacophores have shown various activities against cancer, tuberculosis, malaria, fungal, viral, and bacterial infections. These moieties are considered highly potent nuclei in medicinal chemistry. Thus, this research work aims to produce a synergistic effect involving both nuclei in a single structure. A Series of literature work resulted in the synthesis of novel derivatives of 2‐(1H‐1,3‐benzothiazole‐2‐yl)‐N'‐substituted quinoline‐4‐carbohydrazide 5a–q using a multiple-step reaction. Characterization of all compounds was successfully done using IR and 1HNMR, 13CNMR as well as elemental analysis. Furthermore, screening of all synthesized compounds has been shown a positive response as an anticonvulsant and antidepressant activity in mice. Compounds 5b, 5h, 5l, and 5n have shown potentially active on pentylenetetrazole-induced seizures in mice. The synthesized compounds were also screened on a panel of 60 cell lines by the National Cancer Institute according to standard screening protocol. Ten compounds were selected and evaluated via a single high dose (10−5 M). In a one-dose assay, compounds 5j and 5o showed the highest activity on leukemia (CCRF-CEM) and renal cancer (A498) with growth inhibition (GI) of 70.91 and 61.15%.

Nrf2 is expressed more extensively in neurons than in astrocytes following an acute epileptic seizure in rats.

The modulation of the nuclear factor erythroid 2-like 2 (Nrf2) activity has been reported to be implicated in the pathology of various neurological disorders, including epilepsy. Previous studies have demonstrated that Nrf2 is activated in the post-status epilepticus rat model; however, the spatiotemporal as well as cell type-specific expression of Nrf2 following brief epileptic seizures remains unclear. Here, we evaluated how an acute epileptic seizure affected the expression of Nrf2 and its downstream genes in the rats' cortex and the hippocampus up to 1 week following the induced seizure. We found that after a pentylenetetrazol-induced seizure, Nrf2 significantly increased at 24 h at the mRNA level and 3h at the protein level in the cortex. In the hippocampus, the Nrf2 mRNA level peaked at 3h after the seizure, and no significant changes were observed in the protein level. Interestingly, the mRNA level of Nrf2 downstream genes peaked at 3-6h after seizure in both the cortex and the hippocampus. A significant increase in the expression of Nrf2 was observed in the neuronal population of CA1 and CA3 regions of the hippocampus, as well as in the cortex. Moreover, we observed no change in the co-localization of Nrf2 with astrocytes neither in the cortex nor in CA1 and CA3. Our results revealed that following a brief acute epileptic seizure, the expression of Nrf2 and its downstream genes is transiently increased and peaked at early timepoints after the seizure predominantly in the hippocampus, and this expression is restricted to the neuronal population.

Beneficial effects of sennoside B on pentylenetetrazole-induced seizures in rats.

Epilepsy is a common disorder affecting approximately 50 million people worldwide. Oxidative stress is known to play an important role in the pathophysiology of diseases, including epilepsy. In this study, we investigated the effects of sennoside B on PTZ-induced seizures in rats. The rats were grouped into Group Electroencephalography and Group Behavioral. Both Groups were divided into eight subgroups, and these subgroups were compared in terms of the time of first myoclonic jerk, Racine's Convulsion Scale, malondialdehyde levels, and brain superoxide dismutase activity. The experimental seizure model was performed with pentylenetetrazol. The spike percentage was significantly lower in groups that received sennoside B, and this beneficial effect was shown to be associated with the dose of sennoside B received. The RCS score was lower and the FJM onset time was higher in the sennoside B-administered groups. Additionally, brain MDA and brain aquaporin-3 levels were lower and brain SOD activity was higher in the sennoside-administered groups. The present study shows the beneficial effects of sennoside B on PTZ-induced convulsion in rats. It is considered that sennoside B which is a natural and safe product would be a good candidate for strengthening the management of epilepsy without serious side effects.

Tiagabine suppresses pentylenetetrazole-induced seizures in mice and improves behavioral and cognitive parameters by modulating BDNF/TrkB expression and neuroinflammatory markers

Tiagabine (Tia), a new-generation antiseizure drug that mimics the GABAergic signaling by inhibiting GABA transporter type-1, is the least studied molecule in chronic epilepsy models with comorbid neurobehavioral and neuroinflammatory parameters. Therefore, the current study investigated the effects of Tia in a real-time manner on electroencephalographic (EEG) activity, behavioral manifestations and mRNA expression in pentylenetetrazole (PTZ)-kindled mice. Male BALB/c mice were treated with tiagabine (0.5, 1 and 2 mg/kg) for 21 days with simultaneous PTZ (40 mg/kg) injection every other day for a total of 11 injections and monitored for seizure progression with synchronized validation through EEG recordings from cortical electrodes. The post-kindling protection from anxiety and memory deficit was verified by a battery of behavioral experiments. Isolated brains were evaluated for oxidative alterations and real-time changes in mRNA expression for BDNF/TrkB, GAT-1 and GAT-3 as well as neuroinflammatory markers. Experimental results revealed that Tia at the dose of 2 mg/kg maximally inhibited the development of full bloom seizure and reduced epileptic spike discharges from the cortex. Furthermore, Tia dose-dependently exerted the anxiolytic effects and protected from PTZ-evoked cognitive impairment. Tia reduced lipid peroxidation and increased superoxide dismutase and glutathione levels in the brain via augmentation of GABAergic modulation. PTZ-induced upregulated BDNF/TrkB signaling and pro-inflammatory cytokines were mitigated by Tia with upregulation of GAT-1 and GAT-3 transporters in whole brains. In conclusion, the observed effects of Tia might have resulted from reduced oxidative stress, BDNF/TrkB modulation and mitigated neuroinflammatory markers expression leading to reduced epileptogenesis and improved epilepsy-related neuropsychiatric effects.

Pre-existing Toxoplasma gondii infection increases susceptibility to pentylenetetrazol-induced seizures independent of traumatic brain injury in mice.

Post-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI), and neuroinflammation is implicated in increased seizure susceptibility and epileptogenesis. However, how common clinical factors, such as infection, may modify neuroinflammation and PTE development has been understudied. The neurotropic parasite, Toxoplasma gondii (T. gondii) incurably infects one-third of the world's population. Thus, many TBI patients have a pre-existing T. gondii infection at the time of injury. T. gondii infection results in chronic low-grade inflammation and altered signaling pathways within the brain, and preliminary clinical evidence suggest that it may be a risk factor for epilepsy. Despite this, no studies have considered how a pre-existing T. gondii infection may alter the development of PTE. This study aimed to provide insight into this knowledge gap by assessing how a pre-existing T. gondii infection alters susceptibility to, and severity of, pentylenetetrazol (PTZ)-induced seizures (i.e., a surrogate marker of epileptogenesis/PTE) at a chronic stage of TBI recovery. We hypothesized that T. gondii will increase the likelihood and severity of seizures following PTZ administration, and that this would occur in the presence of intensified neuroinflammation. To test this, 6-week old male and female C57BL/6 Jax mice were intraperitoneally injected with 50,000 T. gondii tachyzoites or with the PBS vehicle only. At 12-weeks old, mice either received a severe TBI via controlled cortical impact or sham injury. At 18-weeks post-injury, mice were administered 40 mg/kg PTZ and video-recorded for evaluation of seizure susceptibility. Fresh cortical tissue was then collected for gene expression analyses. Although no synergistic effects were evident between infection and TBI, chronic T. gondii infection alone had robust effects on the PTZ-seizure response and gene expression of markers related to inflammatory, oxidative stress, and glutamatergic pathways. In addition to this, females were more susceptible to PTZ-induced seizures than males. While TBI did not impact PTZ responses, injury effects were evident at the molecular level. Our data suggests that a pre-existing T. gondii infection is an important modifier of seizure susceptibility independent of brain injury, and considerable attention should be directed toward delineating the mechanisms underlying this pro-epileptogenic factor.

Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

The Anticonvulsant Activity of Mucoadhesive Buccal Films of Sodium Valproate in Pentylenetetrazole-Induced Seizure Rat Model

The Anticonvulsant Activity of Mucoadhesive Buccal Films of Sodium Valproate in Pentylenetetrazole-Induced Seizure Rat Model

Esculetin alleviates pentylenetetrazole-induced seizures, cognitive impairment and pro-inflammatory cytokines and suppresses penicillin-induced epileptiform activity in rats

AimsTo investigate the effects of different doses of esculetin on epileptiform activity, behavioral seizures, memory impairment, and cortical and hippocampal NF-κB, as a mediator of pro-inflammatory gene induction, and pro-inflammatory cytokines in penicillin- and pentylenetetrazole(PTZ)-induced seizure models in rats. Main methodsDifferent doses of esculetin (5, 10, and 20 mg/kg), and diazepam (5 mg/kg) as a positive control, were tested in penicillin- and pentylenetetrazole(PTZ)-induced seizure models. In the PTZ model, cognitive function, behavioral seizures, and cortical and hippocampal pro-inflammatory biomarkers and survival factor was evaluated. In the penicillin model, the frequency and amplitude of electrophysiological epileptiform activity were assessed. Key findingsIn the PTZ model, the 10 mg/kg esculetin displayed anticonvulsant effects by extending onset-times of myoclonic-jerk and generalized tonic-clonic seizure, and by diminishing seizure severity and duration of generalized tonic-clonic seizure. It also ameliorated PTZ-induced cognitive impairment, and cortical and hippocampal activin-A, IL-1β, IL-6 and NF-κB levels. In the penicillin model, the 10 mg/kg esculetin decreased the frequency of spikes without changing the amplitude of spikes. As a positive-control, diazepam reversed all changes induced by both PTZ and penicillin. SignificanceEsculetin exhibits anticonvulsant and memory-improving effects by alleviating the behavioral and electrophysiological characteristics of epileptic seizures. Additionally, esculetin exerts anti-neuroinflammatory actions in the PTZ-induced seizures model. Thus, esculetin may be a multi-targeted promising agent with anticonvulsant and anti-neuroinflammatory effects in the treatment of epilepsy.

Deneysel Epileptik Nöbet Modelinde, Artemisinin'in Fare Kalp ve Akciğer Dokularında Oksidatif Stress Belirteçleri Üzerine Etkisi.

Aim: The current study investigated the effects of artemisinin on the heart and lung tissue against pentylenetetrazol-induced seizures in mice. For this purpose, malondialdehyde (MDA), advanced oxidation protein products (AOPP), Catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels were evaluated in both tissue homogenates.Material and Method: Swiss albino male mice (n=42) were used in the experiment. Animals were divided into six groups; Control (C), pentylenetetrazol (PTZ), valproate 100 mg/kg (VPA), artemisinin 30 mg/kg (ARS)+PTZ, ARS 60 mg/kg+PTZ, ARS 120 mg/kg+PTZ. On the 26th day of the experiment, the mice were sacrificed and the samples were kept at -80 0C for biochemical analysis.Results: There were significant differences in the five biochemical parameters analyzed in heart and lung tissues. Heart and lung MDA levels of the PTZ group were found to be significantly higher than the C and ARS-60 groups (p<0.05). Heart and lung MDA levels of the PTZ group were found to be significantly higher than the C and ARS-60 groups. Likewise, heart AOPP levels decreased significantly in the VPA and ARS-60 groups compared to the PTZ group (p<0.05). There was no significant difference between the groups in terms of lung AOPP levels (p>0.05). Heart CAT and GSH levels were decreased in the PTZ group compared to the other groups. However, in terms of Lung CAT levels, the PTZ group had the highest value compared to the other groups, while it had the lowest value in terms of GSH level. The GSH-Px level did not differ significantly between the groups in heart tissue (p>0.05). The lung GSH-Px level was significantly increased in the ARS-30 group when compared to the PTZ group (p<0.05).Conclusion: Consequently ARS treatment can inhibit PTZ-induced oxidative stress in peripheral tissues. In addition, ARS may provide improvements in decreased antioxidant enzymes. ARS may contribute to the antioxidant defense system.

The anticonvulsant effect of digoxin on basic models of primary generalized seizures does not depend on the route of administration

Improving the prevention and treatment of epilepsy is one of the urgent tasks. Based on the available data on the anticonvulsant activity of the cardiac glycoside digoxin, it is advisable to compare the anticonvulsant effect of the drug by different routes of administration in the experiment. Aim. To determine the impact of the route of administration on the anticonvulsant effect of the cardiac glycoside digoxin on basic models of primary generalized seizures induced by pentylenetetrazol and maximal electric shock. Materials and methods. Two basic models were used: the model of primary generalized convulsions induced in mice by pentylenetetrazol (80 mg/kg subcutaneously) and maximal electric shock (current strength – 50 mA, frequency – 50 Hz, 0.2 sec corneally). Digoxin was administered in the dose of 0.8 mg/kg (about 1/10 LD50) 30 min before modeling seizures in the stomach and subcutaneously. Standard parameters of convulsive syndrome severity and mortality were recorded. Results and discussion. In both seizure models, the anticonvulsant effect of digoxin was little dependent on the route of administration. In the pentylenetetrazole-induced model, with both routes of administration, lethality tended to decrease; when administered intragastrically, digoxin statistically significantly reduced the number of clonic-tonic seizures per 1 mouse, the number of animals with the most severe tonic seizures, and the duration of the convulsive period; when administered subcutaneously, it significantly increased the latent period of seizures and reduced the number of animals with tonic seizures. In the model of maximal electric shock, digoxin reduced seizure severity andlethality almost equally by both routes of administration (by 55 % with the intragastric administration and by 67.5 % with the subcutaneous administration). In both models, there were no statistically significant differences in the course of seizures in both routes of the digoxin administration. With subcutaneous administration, the anticonvulsant effect was somewhat more pronounced at the level of a weak tendency. Conclusions. The anticonvulsant effect of digoxin when administered intragastrically and subcutaneously in mice with models of pentylenetetrazole-induced seizures and maximal electric shock is practically independent of the routeof administration. Digoxin has a pronounced anticonvulsant effect on the model of electrically induced seizures, and a moderate effect on the model of pentylenetetrazole seizures.

Delayed Impairment of Hippocampal Synaptic Plasticity after Pentylenetetrazole-Induced Seizures in Young Rats.

Data on the long-term consequences of a single episode of generalized seizures in infants are inconsistent. In this study, we examined the effects of pentylenetetrazole-induced generalized seizures in three-week-old rats. One month after the seizures, we detected a moderate neuronal loss in several hippocampal regions: CA1, CA3, and hilus, but not in the dentate gyrus. In addition, long-term synaptic potentiation (LTP) was impaired. We also found that the mechanism of plasticity induction was altered: additional activation of metabotropic glutamate receptors (mGluR1) is required for LTP induction in experimental rats. This disturbance of the plasticity induction mechanism is likely due to the greater involvement of perisynaptic NMDA receptors compared to receptors located in the core part of the postsynaptic density. This hypothesis is supported by experiments with selective blockades of core-located NMDA receptors by the use-dependent blocker MK-801. MK-801 had no effect on LTP induction in experimental rats and suppressed LTP in control animals. The weakening of the function of core-located NMDA receptors may be due to the disturbed clearance of glutamate from the synaptic cleft since the distribution of the astrocytic glutamate transporter EAAT2 in experimental animals was found to be altered.

Protective Effect of Metformin Alone or in Combination with Valproic acid on Pentylenetetrazole-Induced Seizures in Mice

Abstract Objective: The aim of this study was to investigate the effects of metformin on pentylenetetrazole (PTZ)-induced seizures and the neuroprotective effect of metformin on neuronal damage after pentylenetetrazole administration. Material and Methods: Thirty-five (35) Male BALB-c Albino mice weighing 35-38 g were divided randomly into five groups: Control group (1), Saline+PTZ group (2), Valproic Acid (VPA, 200 mg/kg intraperitoneal-i.p.)+PTZ group (3), Metformin (200 mg/kg i.p.)+PTZ group (4), and VPA+Metformin+PTZ group (5). The PTZ (60 mg/kg, i.p.) was injected 30 min after drugs injection to induce seizures and seizure stages and behavioral scoring were evaluated. After completing procedure, brain tissues were removed and analyzed with biochemical and histopathological procedures. The hippocampal Cornu Ammonis (CA) 1, CA2, CA3 and DG (dentate gyrus) regions were histopathologically evaluated and oxidative stress markers (total antioxidant status (TAS), total oxidant status (TOS)) were measured. Results: Compare to Saline+PTZ group, metformin administration alone did not affect the onset time of the first myoclonic jerk (FMJ), but combination of VPA and metformin significantly increased FMJ onset time (p<0.05). Additionally, the treatment of metformin with or without VPA reduced the brain oxidative stress (p<0.05). Furthermore, histopathological assessment demonstrated that metformin administration and the combination of VPA and metformin decreased dark neuron formation in the hippocampal CA1, CA2, CA3, and DG areas (p<0.05). Conclusion: Metformin was found to be significantly effective in reducing epileptic seizures, brain oxidative stress, and preventing neural damage after PTZ-induced seizure

SGLT-2 inhibitors as potential anticonvulsants: empagliflozin, but not dapagliflozin, renders a pronounced effect and potentiates the sodium valproate activity in pentylenetetrazole-induced seizures

On the way to the search for effective adjuvant medicines for epilepsy treatment, antidiabetic medicines such as sodium-glucose cotransporter-2 inhibitors, which are expressed not only in the kidneys but also in the brain, attract attention. From previous studies, it is known that dapagliflozin improves electroencephalographic parameters in rats on the model of pentylenetetrazole-induced seizures. However, the anticonvulsant potential of other medicines from this group needs to be clarified.
 The aim of the study is to estimate the effect of empagliflozin, dapagliflozin per se and their combinations with sodium valproate on pentylenetetrazole-induced seizures, as well as on muscle tone and motor coordination in mice.
 Material and methods. 42 random-bred male albino mice weighing 24-28 g were used in the experiments. Empagliflozin (20 mg/kg) and dapagliflozin (50 mg/kg) were administered intragastrically for 3 days. The classic anticonvulsant sodium valproate (150 mg/kg) per se, in combination with the medicines mentioned above, was administered in a similar regimen. On the second day, 30 minutes after administering all medicines, their effect on muscle tone and coordination of movements was determined in the rotarod test. On the third day, 30 minutes after the last administration of the medicines, their effect on pentylenetetrazole-induced (80 mg/kg subcutaneously) seizures was studied.
 Results. For the first time, a pronounced anticonvulsant effect of empagliflozin was established both when used alone (a significant increase in latency of the convulsions and a decrease in lethality by 43 %) and especially in combination with sodium valproate (a significant increase in latency of the convulsions, a decrease in the number and severity of seizures and a decrease in lethality by 83 %), as well as the absence of a muscle relaxant effect in both cases. Dapagliflozin has neither its anticonvulsant properties nor its effect on the action of sodium valproate. However, this medicine caused muscle relaxation, especially when combined with sodium valproate.
 Conclusions. The results suggest that empagliflozin, unlike dapagliflozin, has a high potential as an adjuvant medicine in treating epilepsy, as it enhances the efficacy of the classic anticonvulsant sodium valproate without muscle relaxant side effects

Pentylenetetrazol-induced seizures are followed by a reduction in the multiunitary activity of hippocampal CA1 pyramidal neurons in adult rats

Pentylenetetrazol (PTZ) blocks the inhibitory action of GABA, triggering a Glu-mediated hyperexcitation of the dendritic spines in hippocampal CA1 pyramidal neurons that leads to the generation of epileptiform seizures. The aim of this work was to determine the effect of PTZ on the electrical activity of the hippocampal pyramidal neurons in male rats. Bipolar electrodes were implanted stereotaxically in the right and left hippocampal CA1 fields of adults, and PTZ (65 mg/kg) was administered i.p. Simultaneous recordings of the field activity and the firing rate (multiunitary activity, MUA) were analyzed at 10, 20, and 30 min post-administration of PTZ. Only rats that presented tonic-clonic seizures during the first 1–5 min after PTZ treatment were included in the study. The recordings of the field activity were analyzed in 4 frequency bands. In both the right and left hippocampal CA1 fields, the relative power corresponding to the slow waves (4–7 Hz) increased, while in the bands 13–30 Hz and 31–50 Hz, it decreased at 10, 20, and 30 min post-PTZ. MUA recordings were analyzed at four levels. The highest levels corresponded to larger amplitudes of the action potentials in the pyramidal neurons. The firing rates of the PTZ-treated rats did not differ from baseline but presented a significant decrement at 10, 20, and 30 min post-PTZ. The decreased firing rate of the hippocampal CA1 pyramidal neurons after PTZ treatment could be associated with plastic changes of dendritic spines along with some microenvironmental adaptations at synaptic level, after neuronal PTZ-mediated hyperexcitation.

Stem bark chloroform extract of Bombax costatum Pellegr. & Vuillet exhibit anticonvulsant and neuroprotective effects in pentylenetetrazole-induced seizures in rats

The study aimed at evaluating the potentials of stem bark extracts of Bombax costatum (B.costatum) on seizure, pentylenetetrazole (PTZ) induced kindling and associated changes in wistar albino rats. Phase 1 evaluated which extract of B.costatum (chloroform, ethanol and n-hexane) is most effective in preventing seizure in acute PTZ-induced (85mg/kg) seizure in rats. Phase 2 evaluated the potentials of stem bark chloroform extract of B.costatum in PTZ-kindled rats at a dose 250 and 500mg/kg in comparison to diazepam. As its effects on memory, oxidative stress markers, neurotransmitters and brain histology were evaluated. Phase 3 determined the probable curative effects of B.costatum on fully kindled rats. In phase 1, Chloroform extract of B.coststum 500mg/kg is the most effective (P<0.05) in preventing seizure as compared to ethanol and n-hexane extracts. In phase 2, chloroform extract of B.costatum delayed the development of kindling, improved kindling associated cognitive impairment and alterations of glutamate and gamma-aminobutyric acid (GABA). Further, it attenuated oxidative stress besides the maintenance of neuronal architecture of the hippocampus. Conclusively, chloroform stem bark extract of B.costatum antagonizes PTZ-induced seizure progression, protects against kindling induced cognitive impairment and oxidative stress. Additionally, it also increases the brain level of GABA at high dose and prevented against kindling-induced hippocampal disruptions. Hence, this justifies its use traditionally in the treatment of epileptic seizures.

A comparative brain Toxico-Pharmacokinetics study of a developed tannic acid nanoparticles in the treatment of epilepsy

Epilepsy is the most popular neurological problem throughout the world. Tannic Acid (TA) is used with vitamin E (antioxidant) as desirable and safe in the treatment of epilepsy. We used central composite design (CCD) to optimize for the preparation of PLGA Nanoparticles (NPs) in the delivery of TA via intranasal to brain which gives results improvement of brain bioavailability. PLGA NPs was prepared through an emulsion solvent evaporation with the help of 3-factor, 4-level CCD to get a best optimized-NPs. 3-independent variables were chosen (PLGA, Vitamin E TPGS, and sonication time) for the optimization of best NPs. Coating of TA-PLGA-NPs with chitosan was done for enhanced antiepileptic efficacy and brain targeting as well as drug release followed by nasal permeation study. An optimized-NPs was optimized by the two variables (dependent and independent) based on the composition of PLGA (3.0%), Vitamin E TPGS (0.3%), and sonication time (5.0 min). The values of particle size, entrapment efficiency, PDI, and zeta potential were found 105.7 ± 11.02 nm, −22.3 ± 2.3 mV, 0.169 ± 0.002, and 69.31 ± 5.89% respectively based on selected dependent variables. Optimized-TA-PLGA-NPs were coated by the CS that gives the negative to positive ZP value followed by small increment of PS. On the basis of brain pharmacokinetics results, we found a great significantly (p < 0.001) enhancement of Cmax and area under curve (AUC)0–24 by treatment (intranasal and i.v.) of wistar rats. Finally, we found a great significant i.e. p < 0.001 results in the treatment of epilepsy models (increasing current electroshock & pentylenetetrazole-induced seizures with the administration of CS coated TA PLGA NPs due to their great mucoadhesive property. we also found a significant i.e. p < 0.001) enhancement of brain-bioavailability of TA followed by treated epilepsy rats due to the administration of CS coated TA PLGA NPs. There were no mortalities, neither variation morphologically of microstructure-of brain-as well as nasal-mucosa- tissues. We didn't observe no visual signs of inflammatory or necrosis that means no toxicological results.

Mentha piperita Oil Exerts an Antiepileptic Effect in Pilocarpine and Pentylenetetrazol-Induced Seizures in Mice.

Introduction Epilepsy is a progressive, chronic neurological disorder characterized by recurrent seizures. Peppermint (Mentha piperita L.) (MP) is one of the most commonly ingested herbal teas or tisanes with a single component. Aim We aimed to assess the potential antiepileptic and neuroprotective features of MP essential oil (MPO) in pilocarpine (P) and pentylenetetrazol (PTZ) models of epilepsy. Methods The study used eight groups of mice to assess the anticonvulsant activity of MPO in both the P and PTZ acute models in mice. P (350 mg/kg, i.p.) was given 30 minutes after MPO (1.6, 3.2, and 6.4 ml/kg, i.p.). As a positive control group, diazepam (1 mg/kg, i.p) was used. PTZ (95 mg/kg, i.p.) was given 30 minutes after MPO (6.4 ml/kg, i.p.). The first convulsion's latency time, the number of convulsions, the latency time to death, and the percentage of deaths were calculated in all groups. Results MPO significantly (P < 0.05) increases the first convulsion's latency time and the death's latency time. Moreover, the essential oil significantly decreases the number of convulsions and reduces the mortality rate compared to the negative control group. Conclusion MPO at 3.2 and 6.4 ml/kg doses can reduce the percentage and the number of convulsions and increase the latency time of both the first convulsion and death so that it can be used as a supplement in the treatment of epilepsy.

Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.

The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ). We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number. PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects. Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.