Pentylenetetrazole-induced Kindling Research Articles

The effect of Zataria multiflora Boiss hydroalcoholic extract and fractions in pentylenetetrazole-induced kindling in mice.

At present, there are many antiepileptic drugs with a wide range of side effects on the human body. It was assumed that Zataria multiflora Boiss (Z. multiflora) with sedative, anti-spasmodic and anti-inflammatory activity may be effective in the treatment of epilepsy. The aim of the present study was to elucidate the effect of Z. multiflora hydroalcoholic extract and its fraction extracts on pentylenetetrazole (PTZ)-induced chemical kindling. In this experimental study, eight separate groups of male albino mice were used. All groups received 11 separate intraperitoneal injections of PTZ (35 mg/kg) with two-day intervals. 30 min before the injection of PTZ, mice received vehicle, Z. multiflora hydroalcoholic extract (300 and 600 mg/kg), n-hexane, acetone, methanol fraction extracts (150 mg/kg), or diazepam (10 mg/kg). The kindled mice that were pretreated with vehicle showed a gradual increase in their seizure scores up to the end of the study. The hydroalcoholic extract of Z. multiflora (300 and 600 mg/kg) reduced seizure scores significantly. However, n-hexane, acetone and methanol extracts did not affect seizure scores significantly. The present findings demonstrate that the hydroalcoholic extract of Z. multiflora did reduce the severity of seizure attacks in PTZ-induced chemical kindling in mice.

Protective Effect of Nerolidol Against Pentylenetetrazol-Induced Kindling, Oxidative Stress and Associated Behavioral Comorbidities in Mice

The present study was aimed to investigate the effect of nerolidol on the development of kindling and associate oxidative stress and behavioral comorbidities. Kindling was induced by repeated injections of a sub-convulsive dose of pentylenetetrazol (PTZ-35mg/kg; i.p.), at an interval of 48 ± 2h for 43days (21 injections). Nerolidol was administered daily in three doses (12.5, 25 and 50mg/kg) along with alternate day PTZ injection. To access behavioral comorbidities, animals were subjected to tail suspension test (TST) and passive shock avoidance (PSA) test to evaluate the associated depression and memory impairment respectively on the last day of PTZ administration. Following behavioral assessment, neurotransmitter level and oxidative stress markers were evaluated in brain. The results showed that nerolidol significantly suppressed the progression of kindling. Also, nerolidol ameliorates the kindling associated depression and memory impairment as indicated by decreased immobility time and increased step down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complimented with corresponding neurochemical and oxidative stress markers changes. In conclusion, the results of present study showed that nerolidol treatment has protective effect against PTZ-induced kindling and associated oxidative stress and behavioral comorbidities.

Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats.

Epilepsy is the third most common cause of neurological disability worldwide. Despite the introduction of antiepileptic drugs (AEDs) in the past 20years, the seizures of around 30% of patients with epilepsy remain refractory to available treatment. Also, available AEDs and the disease itself have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. S-adenosyl methionine has potential antiepileptic and memory-enhancing properties because of its involvement in the transmethylation reaction. The present study was designed to evaluate the antiepileptic effect of S-adenosyl methionine and its role in memory impairment in the pentylenetetrazole (PTZ)-induced kindling model in rats. The antiepileptic effect of 2 doses of SAM (50 and 100mg/kg) was tested by evaluating seizure severity score and seizure latency in the pentylenetetrazole-induced kindling model in rats. At the end of the study, spatial memory was evaluated in an elevated plus maze (EPM) test, and animals were sacrificed for estimation of oxidative stress markers in brain tissue homogenate. A higher dose of SAM (100mg/kg) exhibited an increase in seizure latency and a decrease in seizure severity score, suggesting its antiepileptic activity in the PTZ-induced kindling model. Also, the administration of SAM (50 and 100mg/kg) showed a decrease in transfer latency in the EPM test compared to the disease control group (p<0.0001). Biochemical analysis of rat brain tissue revealed significantly decreased malondialdehyde (p<0.0001) and increased glutathione (GSH) (p<0.0001) in the SAM 100-mg/kg group compared with that in the disease control group. The results demonstrated that S-adenosyl methionine exerts antiepileptic, memory-enhancing, and antioxidant properties in a pentylenetetrazole-induced kindling model of epilepsy.

Expression of TRPV1 Receptors Increased in Hippocampus Following Pentylenetetrazole-Induced Kindling in Male Rats

Background: The exact pathogenesis of epilepsy is not clear well. Recent studies showed the possible involvement of transient receptor potential vanilloid type 1 (TRPV1) receptors in this disease. Objectives: The aim of this study was to measure the expression of TRPV1 receptors in hippocampus following pentylenetetrazole (PTZ)-induced kindling in male rats. Materials and Methods: In this experimental study, 14 male Wistar rats were allocated into two groups of experimental and control (seven rats in each group). The kindling group received a subconvulsive dose of PTZ (35 mg/kg, intraperitoneally) every 48 hours for 15 sessions, while the control rats were injected with an equal dose of saline. At the end of the injections, rats were decapitated, and their brains were removed. TRPV1 receptor expression in hippocampus region was assessed by real-time polymerase chain reaction method. Results: The results of the current study showed that expressions of TRPV1 receptors were increased in hippocampus following PTZ-induced kindling in male rats. Conclusions: Since the expression of TRPV1 receptors increased in hippocampus of epileptic rats, the TRPV1 receptors may be good candidates for epilepsy treatment.

Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities.

Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice.

Borneol, a bicyclic monoterpene, can easily cross the blood brain barrier and was found to possess gamma amino butyric acid (GABA) modulatory effect. The present study was aimed at investigating the antiepileptogenic effect of borneol in the pentylenetetrazole (PTZ)-induced kindling besides its ability to suppress oxidative stress and neuroinflammatory marker, glial fibrillary acidic protein (GFAP). Repeated administration of a subconvulsive dose of PTZ (35 mg/kg, i.p.) on every alternate day for 4 weeks produced kindling in mice. Borneol (5, 10, and 25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were given as a pretreatment prior to each PTZ injection during the progression of kindling. Oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and lipid peroxidation (LPO) were assessed at the end of the study. Neuronal damage was assessed by hematoxylin and eosin staining technique. GFAP was also evaluated in the hippocampus region of the brain by using immunohistochemistry. Borneol significantly suppressed the process of epileptogenesis in PTZ-kindled mice. The biochemical alterations induced by PTZ kindling were ameliorated in borneol-treated animals which was indicated by decreased LPO and increased SOD, GSH, CAT levels. The distinct neuronal damage observed in the kindled group was counteracted by borneol. Furthermore, it decreased the levels of GFAP which was manifested by reduced immunostaining. The above results are suggestive of the antiepileptogenic potential of borneol in the PTZ-induced kindling model of epilepsy, and thus, it could be a prospective molecule in the treatment of epilepsy.

Antiepileptic Activity of a New Derivative of Benzimidazole RU-1205.

Antiepileptic activity of a new derivative of benzimidazole RU-1205 was studied on the model of pentylenetetrazole-induced generalized seizures in mice. Sodium valproate was used as the reference substance. RU-1205 was superior to sodium valproate by anticonvulsant activity (by 12 times) and therapeutic index (by 8.5 times). In contrast to sodium valproate, RU-1205 exhibited significant anticonvulsant activity on the model of pentylenetetrazole-induced kindling without tendency to resistance development.

Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice

Neurosteroids, such as testosterone and their metabolites, are known to modulate neuronal excitability. The enzymes regulating the metabolism of these neurosteroids, thus, may be targeted as a noval strategy for the development of new antiepileptic drugs. The present work targeted two such enzymes i,e aromatase and 5α-reductase in order to explore the potential of letrozole (an aromatase inhibitor) on pentylenetetrazole (PTZ)-induced kindling in mice and the ability of finasteride (a 5α-reductase inhibitor) to modulate any such effects. PTZ (30 mg/kg, i.p.), when administered once every two days (for a total of 24 doses) induced kindling in Swiss albino mice. Letrozole (1 mg/kg, p.o.), administered prior to PTZ, significantly reduced the % incidence of kindling, delayed mean onset time of seizures and reduced seizure severity score. Letrozole reduced the levels of plasma 17β-estradiol after induction of kindling. The concurrent administration of finasteride and letrozole produced effects similar to letrozole on PTZ-kindling and on estradiol levels. This implies that the ability of letrozole to redirect the synthesis of dihydrotestosterone (DHT) and 5α-androstanediol from testosterone doesn't appear to play a significant role in the protective effects of letrozole against PTZ kindling. Letrozole, however, increased the levels of 5α-DHT in mice plasma. The aromatase inhibitors, thus, may be exploited for inhibiting the synthesis of proconvulsant (17β-estradiol) and/or redirecting the synthesis of anticonvulsant (DHT and 5α-androstanediol) neurosteroids.

Effects of a lyophilized aqueous extract of Feretia apodanthera Del. (Rubiaceae) on pentylenetetrazole-induced kindling, oxidative stress, and cognitive impairment in mice

Feretia apodanthera Del. (Rubiaceae) is extensively used in ethnomedicine in Cameroon and Nigeria for epilepsy, febrile convulsions, and rheumatic pains and for enhancing cognitive performance. The aim of the present study was to examine the effects of a lyophilized aqueous extract of F. apodanthera on the course of kindling development, kindling-induced learning deficit, oxidative stress markers, and cholinesterase activity in pentylenetetrazole (PTZ)-kindled mice. Pentylenetetrazole, 30mg/kg, induced kindling in mice after 30.00±1.67days. The aqueous extract of F. apodanthera showed dose-dependent antiseizure effects. Feretia apodanthera (150–200mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures, and generalized tonic–clonic seizures. The extract also improved the seizure score and decreased the number of myoclonic jerks. Pentylenetetrazole kindling induced significant oxidative stress and cognitive impairment which were reversed by pretreatment with F. apodanthera in a dose-dependent manner. The significant decrease in cholinesterase activity observed in the PTZ-kindled mice was reversed by pretreatment with the F. apodanthera extract. The results indicated that pretreatment with the aqueous extract of F. apodanthera antagonizes seizures, oxidative stress, and cognitive impairment in PTZ-kindled mice. The aqueous extract of F. apodanthera also showed anxiolytic activities, but the inhibition of memory impairment was not attributed to the anxiolytic activities of the plant. These results thus suggest the potential of F. apodanthera as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure-induced oxidative stress and memory impairment.

Protective Effects of Diosgenin in Pentylenetetrazole Induced Kindling Model of Epilepsy in Mice

The present study was aimed at investigating the effects of Diosgenin, a plant derived steroidal sapogenin on the development and acquisition of pentylenetetrazole (PTZ) kindling along with altered biochemical parameters. Diosgenin (5 and 10 mg/kg, i.p.) was evaluated on the course of kindling development and its ability to suppress the PTZ induced oxidative damage in the brain tissue when given as a pretreatment prior to each PTZ injection. Various oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and lipid peroxidation (MDA) were assessed at the end of the study. Neuronal damage was studied by hematoxylin and eosin (H&E) staining technique. The neuroinflammatory marker glial fibrillary acidic protein (GFAP) was also evaluated at the end of the study using immunohistochemistry. Diosgenin significantly prevented the process of epileptogenesis in PTZ induced kindling model as exhibited by lower seizure score. The biochemical alterations induced by PTZ were ameliorated in diosgenin treated animals which was indicated by decreased MDA and increased SOD, GSH, CAT levels. Diosgenin treatment protected the neurons from seizure induced damage. It also alleviated the levels of GFAP which was manifested by reduced immunostaining. The above results are suggestive of the neuroprotective potential of Diosgenin which can be correlated with its ability to not only suppress oxidative damage but also to reduce seizure generation and further damage associated with the same. Diosgenin, thus could be a promising candidate in mitigating the sequel of events implicated in the progression of epileptic disorder/seizures.

Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model.

Studies in the animals suggested that Peroxisome proliferators activated receptors (PPARs) may be involved in seizure control and selective agonists of PPAR α or PPAR γ raise seizure thresholds. The present study was contemplated with the aim of evaluating the anti kindling effects and the mechanism of bezafibrate, a Peroxisome proliferator-activated receptors α (PPAR-α) agonist in pentylenetetrazole (PTZ) induced kindling model of seizures in rats. In a PTZ kindled Wistar rat model, different doses of bezafibrate (100 mg/kg, 200 mg/kg and 300 mg/kg) were administered intraperitoneally 30 minutes before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were the latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal lipid peroxidation studies, serum neuron specific enolase, and hippocampal DNA fragmentation study. In this study, bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures. In the present study bezafibrate decreased the thiobarbituric acid-reactive substance i.e. Malondialdehyde levels, increased the reduced glutathione levels, catalase and superoxide dismutase activity in the brain. This added to its additional neuroprotective effects. Bezafibrate also reduced the neuronal damage and apoptosis in hippocampal area of the brain. Therefore bezafibrate exerted anticonvulsant properties in PTZ induced kindling model in rats. These findings may provide insights into the understanding of the mechanism of bezafibrate as an anti kindling agent and could offer a useful support to the basic antiepileptic therapy in preventing the development of PTZ induced seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy.

Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats.

Numerous studies have demonstrated the antioxidant effects of grape seed proanthocyanidin extract (GSPE). The generation of free radicals and the ensuing apoptosis may contribute to the pathogenesis of epilepsy; therefore, in the present study, we examined the effects of GSPE on cognitive impairment and neuronal damage induced by chronic seizures in rats. Seizures were induced by a daily intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ; 35 mg/kg/day, 36 days). Two other groups were treated with GSPE (100 or 200 mg/kg/day, orally) for 24 days and then for 36 days prior to each PTZ injection. After the final PTZ injection, hippocampus-dependent spatial learning was assessed using the Morris water maze (MWM). The rats were then sacrificed for the measurement of hippocampal malondialdehyde (MDA, a measure of lipid peroxidation) and glutathione (GSH, a measure of endogenous antioxidant capacity) levels, and for the expression of pro-apoptotic factors [cytochrome c (Cyt c), caspase-9 and caspase-3]. The mitochondrial generation of reactive oxygen species (ROS), degree of mitochondrial swelling, neuronal damage and mitochondrial ultrastructure were also examined. Performance in the MWM was markedly impaired by PTZ-induced seizures, as evidenced by longer escape latencies during training and fewer platform crossings during the probe trial. This cognitive decline was accompanied by oxidative stress (MDA accumulation, ROS generation, reduced GSH activity), an increased expression of pro-apoptotic proteins, as well as damage to CA1 pyramidal neurons and the mitochondria. Pre-treatment with GSPE dose-dependently reversed PTZ-induced impaired performance in the MWM, oxidative stress, mitochondrial ROS generation, the expression of pro-apoptotic proteins and neuronal and mitochondrial damage. Thus, GSPE may reverse the hippocampal dysfunction induced by chronic seizures, by reducing oxidative stress and preserving mitochondrial function.

Dynamic expression patterns of ATF3 and p53 in the hippocampus of a pentylenetetrazole-induced kindling model.

Epilepsy is a common and often deleterious neurological condition. Emerging evidence has demonstrated the roles of innate immunity and the associated inflammatory processes in epilepsy. In a previous study, we found that Toll-like receptors (TLRs) are upregulated and promote mossy fiber sprouting (MFS) in an epileptic model. As downstream effectors of TLRs, the activating transcription factor 3 (ATF3) and p53 proteins were shown to be involved in neurite outgrowth. In the present study, we hypothesized that ATF3 and p53 participate in the process of epilepsy and can affect MFS. To investigate this hypothesis, we examined the expression of ATF3 and p53 in hippocampal tissues of rats kindled by pentylenetetrazole (PTZ) using immunofluorescence, immunohistochemistry and western blotting. MFS was evaluated by Timm staining in the hippocampus. Results from these experiments revealed that expression of ATF3 and p53 is significantly higher (p<0.05) in the CA3 area of the hippocampus in the PTZ-treated group compared to the control group. ATF3 expression gradually increased from 3 days to 4 weeks, peaked at 4 weeks and decreased slightly at 6 weeks in the PTZ group, while the expression of p53 was maintained at similar levels at different time-points following PTZ treatment. No obvious difference in the expression of these proteins was observed between the PTZ and the control group in the dentate gyrus (DG) area (p>0.05). The degree of MFS in the PTZ group peaked at 4 weeks and was maintained at a high level until 6 weeks post-PTZ treatment. In conclusion, ATF3 and p53 may be involved in the occurrence of seizure and play critical roles in MFS in the PTZ kindling model.

Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice

Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.

The role of interleukin-1β in the pentylenetetrazole-induced kindling of seizures, in the rat hippocampus

Because the contribution of inflammatory mediators to seizure disorders is unclear, we investigated the changes in the expression of interleukin-1β (IL-β) and its receptor – IL-1 receptor type 1 (IL-1R1), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the rat hippocampus at different stages of pentylenetetrazole (PTZ)-induced kindling. The occurrence and progressive development of seizures were induced by repeated systemic administration of PTZ, a non-competitive antagonist of the γ-aminobutyric acid type A (GABAA) receptor at a subconvulsive dose of 30mg/kg. We also examined the effects of continuous intracerebroventricular administration of IL-1β and lipopolysaccharide (LPS) in this model of epilepsy using subcutaneously implanted osmotic mini-pumps. We observed enhanced IL-1R1 expression in the dentate gyrus (DG) at different stages of kindling, whereas the elevated IL-1β level was distinctive to fully kindled seizures. We did not detect significant changes in the concentration of IL-6 or TNF-α throughout the kindling process. LPS accelerated transiently the process of kindling, while IL-1β showed a predisposition to delay kindling acquisition. Our study supports the concept of seizure-related modifications in brain cytokine production during epileptogenesis. Although some evidence indicates a proconvulsant property of IL-1β activity, it cannot be ruled out that the alterations in IL-1 system reflect the activation of endogenous protective mechanisms with respect to the kindling of seizures.

Understanding the anti-kindling role and its mechanism of Resveratrol in Pentylenetetrazole induced-kindling in a rat model

BackgroundResveratrol is a polyphone chemical found in a number of plant species, including peanuts and grapes, but with significant amounts in red wine. In normal plant physiology, Resveratrol is produced as a defensive response to injury or parasitic attacks. Resveratrol has diverse biological properties and actions with potential clinical applications, including anti-inflammatory, antioxidant, anti proliferative, and neuroprotective effects. AimThe aim of the present study was to explore the effect and mechanism of Resveratrol in Pentylenetetrazole (PTZ) induced kindling in rats. Materials and methodsIn a PTZ kindled Wistar rat model, different doses of Resveratrol (25mg/kg, 50mg/kg and 75mg/kg) were administered orally 30min before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10weeks. The following parameters were compared between control and various experimental groups: the course of kindling, stages of seizures, histopathological scoring of hippocampus, antioxidant parameters, DNA fragmentation and caspase-3 expression in the hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer's Exact test were used for statistical analyses. The resultsIn the present study, Resveratrol showed dose-dependent anti-seizure effect. Resveratrol (75mg/kg) significantly increased the latency to myoclonic jerks, clinic seizures as well as generalized tonic-clinic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ induced kindling caused a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with Resveratrol in a dose-dependent manner. ConclusionOur study suggests that Resveratrol has a potential antiepileptogenic effect on PTZ-induced kindling in rats. The possible underlying mechanisms of Resveratrol as an antiepileptic agent may be due to its antioxidative property and neuroprotective effect.

Lamotrigine Decreased Hippocampal Damage and Improved Vascular Risk Markers in a Rat Model of Pentylenetetrazole Induced Kindling Seizure

Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.

Characterization of anticonvulsant and antiepileptogenic potential of thymol in various experimental models

The present study was to investigate the anticonvulsant and antiepileptogenic potential of thymol. Anticonvulsant activity of thymol (5-100mg/kgi.p.) was studied using maximal electroshock, pentylenetetrazole (PTZ), strychnine and 4-aminopyridine (4-AP) models. Thymol at the selected dose was also studied for its effect on locomotion. Antiepileptogenic property of thymol (5-25mg/kg) was evaluated using PTZ-induced kindling model along with its effect on malondialdehyde and glutathione levels. Thymol (50 and 100mg/kg, i.p.) showed anticonvulsant activity against maximal electroshock and pentylenetetrazole (66.66 and 83.33% protection at 50 and 100mg/kg, respectively) model but not against strychnine and 4-aminopyridine models. Thymol exhibited decreased locomotor activity in dose-dependent manner at the same dose range. Thymol at the dose of (25mg/kg, i.p.) significantly decreased the seizure score, increased glutathione levels and decreased malondialdehyde levels in pentylenetetrazole-induced kindling model. Thymol exhibited significant anticonvulsant and antiepileptogenic property.

Heart Rate Regulation at Different Levels of Convulsive Readiness

Heart rate variability parameters and the level of convulsive readiness during pentylenetetrazole-induced kindling in rats were analyzed using telemetric ECG and EEG monitoring. Analysis of ECG recorded over many days showed that heart rate variability was equally reduced after 7 and 27 days of kindling irrespective of the level of convulsive readiness. Reduced sympathovagal index after 7 days of kindling showed the compensatory character of changes. However, compensatory mechanisms cannot prevent high risk of life-threatening arrhythmias. High convulsive readiness after 27 days of kindling was accompanied by a shift of autonomic balance towards the increase in sympathetic tone, which may lead to decompensation and transition to a prenosological state.

Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice

Ethnopharmacological relevanceRepeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia. However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy. Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model. Materials and methodsLavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development. Valproate (Val), a major antiepileptic drug, was also tested for comparison. ResultsVal and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality. In this regard, Lavandula officinalis was more effective than Val. Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group. Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group. ConclusionThis is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model. In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression.