Duration Of Clonic Convulsions Research Articles

Oleanolic acid suppresses pentylenetetrazole-induced seizure in vivo

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

Anticonvulsant activities of Quercus infectoria (galls) and Trewia nudiflora (seeds) in Nepalese varieties

Background and objectives: Epilepsy is defined as the heterogeneous, synchronized abnormal electrical discharge from the brain area. The numerous synthetic antiepileptic drugs currently available are ineffective to many patients and plant-derived drugs could be an alternative. The aim of this study was to evaluate anticonvulsant activities of Quercus infectoria (galls) and Trewia nudiflora (seeds) found in Nepal. Materials and methods: Anticonvulsant activity was carried out using Isoniazide-induced clonic convulsion (INH 250 mg/kg) using rat model. Onset and duration of clonic convulsion, percentage protection and death were observed. Results: T. nudiflora showed a dose dependent hindrance on the onset of clonic convulsions when compared with the control group. Treatment with higher doses of T. nudiflora (400 mg/kg) showed significant increase (p < 0.01) in latency of clonic convulsions whereas, lower dose showed significant increase (p < 0.05) in latency of clonic convulsion. The extract of T. nudiflora protected 25% of animals from convulsion at a dose 400 mg/kg. However, Q. infectoria did not display dose dependent delay on the onset of clonic convulsion, Q. infectoria (100 and 400 mg/kg) showed insignificant increases in latency of clonic convulsions. The extract of Q. infectoria protected the 25% of animals when used at a lower dose of 100 mg/kg. Positive control group treated with diazepam at a dose 4 mg/kg showed 100% protection from clonic seizures and death. Q. infectoria (100 mg/kg) T. nudiflora (400 mg/kg) and Diazepam (4 mg/kg) showed significant decrease (p<0.01) in seizure duration (s). Q. infectoria (400 mg/kg) and T. nudiflora (100 mg/kg) showed significant decrease (p < 0.05) in seizure duration compared to control group (Normal saline 10 ml/kg). Study reports the antiepileptic effects Q. infectoria and T. nudiflora. Conclusion: The methanolic extract galls of Q. infectoria and seeds of T. nudiflora showed protective effect on Isoniazide induced convulsion.

The antiepileptic potential of Vateria indica Linn in experimental animal models: Effect on brain GABA levels and molecular mechanisms

BackgroundEpilepsy is a neurodegenerative condition characterized by uncontrollable convulsions caused by a misalignment of the central nervous system's inhibitory and excitatory branches. Vateria indica is a medicinal herb with anti-inflammatory, anthelmintic, antiulcer, antitumor, and anticancer properties. ObjectivesTo investigate the antiepileptic activity of Vateria indica using maximal electrical shock (MES), pentylenetetrazole (PTZ), and isoniazid (INH) induced experimental animal models. MethodologyVateria indica bark was subjected to Soxhlet extraction using ethanol and quantitative and qualitative analysis was performed. The antiepileptic activity of Vateria indica bark extract (VIE) was investigated using different animal models in mice. GABA levels in the brain and antioxidant capacity in vitro were estimated. ResultsTreatment of mice with VIE significantly reversed the MES-induced convulsions, which was reflected by the decrease in the duration (sec) of all the phases of MES-induced convulsions, with an increment in the GABA levels. In the PTZ and INH models, pretreatment with VIE delayed the latency to clonic convulsions (p 0.001), reduced the intensity and duration of clonic convulsions, and reduced the mortality rate in the treatment groups in a dose-dependent manner. VIE intervention dose-dependently restored brain GABA levels. VIE also exhibited significant in-vitro antioxidant activity. ConclusionOverall, the findings imply that Vateria indica has substantial antiepileptic activities, mediated by positive GABAergic neurotransmission and antioxidant capabilities. To summarize, Vateria indica may provide adequate protection against epileptic seizures, suggesting that it could be used to treat petitmal and grandmal epilepsy. We plan to provide pure lead compounds derived from Vateria indica in the future in order to better understand the role it could play in the development of natural anticonvulsant drugs.

Effect of calcium channel blocker as anticonvulsant and its potentiating effect when used along with sodium valproate in pentylenetetrazole induced seizures in Albino rats

Background: Many antiepileptic drugs were introduced for the treatment of epilepsy. Ideal antiepileptic drug should not only prevent but also correct the underlying pathophysiology without altering the normal neurotransmission. Calcium channel blockers may form such group because initiation of seizure is associated intrinsic burst firing which is triggered by large inward calcium current, so this study was done to evaluate the anticonvulsant effect of amlodipine in albino rats.Methods: A total of 42 adult albino rats were included in the study and divided into 7 groups, each containing 6 rats. Group 1 received distilled water, group 2,3 received sodium valproate 50mg/kg and 100mg/kg, group 4-6 received amlodipine 1, 2, 4mg/kg and group 7 received combination of Amlodipine 1 mg/kg and sodium valproate 50mg/kg. Pentylenetetrazole induced seizures model was done and onset of myoclonic jerks, onset of clonic convulsions and duration of clonic convulsions was studied.Results: There was a significant anticonvulsant effect in Amlodipine doses 2, 4mg/kg (p <0.001). The combination of Amlodipine (1mg/kg) and Sodium valproate (50mg/kg) also had significant anticonvulsant effect.Conclusions: Amlodipine, a calcium channel blocker has anticonvulsant effect and also potentiated the anticonvulsant effect of low dose sodium valproate.

Anticonvulsant and Antioxidant Effects of Musa sapientum Stem Extract on Acute and Chronic Experimental Models of Epilepsy.

Background:Musa sapientum (banana) plant extract has been shown to possess antioxidant activity in previous studies. Neuronal injury resulting from oxidative stress is an important factor involved in pathogenesis of epilepsy.Objective:The present study aimed to evaluate the anticonvulsant activity of M. sapientum stem extract (MSSE) in acute and chronic experimental models in mice and its effects on various markers of oxidative stress in the brain of pentylenetetrazole (PTZ)-kindled animals.Material and Methods:Maximal electroshock seizures (MES) and PTZ-induced convulsion models were used for acute studies. For the chronic study, the effect of MSSE on the development of kindling was studied. For the evaluation of the effects of MSSE on oxidative stress in brain, malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the brains of the kindled animals.Results:MSSE significantly increased the latency to onset of myoclonic jerks and the duration of clonic convulsions following PTZ administration. The MSSE pretreated group showed significantly reduced mean seizure score on PTZ-induced kindling. There was a significant increase in the brain MDA levels and decrease in GSH levels in response to PTZ-induced kindling. On MSSE pretreatment, there was a significant decrease in the MDA levels in the brains, though the increase in the GSH levels was not significant.Conclusion:The results from this study suggest the presence of significant anticonvulsant activity in MSSE, in both acute and chronic PTZ-induced seizure models, which could be due to its antioxidant activity, as is reflected by the change in oxidative stress markers in brain.SUMMARY Evaluation of the anticonvulsant activity of Musa sapientum and its effects on various markers of oxidative stress in the brain has not been done previously to the best of our knowledgeM. sapientum stem extract (MSSE) significantly increased the latency to onset of myoclonic jerks and the duration of clonic convulsions in the experimental modelsThe MSSE pretreated group showed significantly reduced mean seizure score on pentylenetetrazole (PTZ)-induced kindlingThere was significant increase in the brain malondialdehyde (MDA) levels and decrease in glutathione (GSH) levels in response to PTZ-induced kindlingOn MSSE pretreatment, there was a significant decrease in the MDA levels in the brain, though the increase in the GSH levels was not significant. Abbreviations Used: MSSE: Musa sapientum stem extract, PTZ: Pentylenetetrazole, MES: Maximal electroshock seizures, MDA: Malondialdehyde, GSH: Glutathione, SOD: Superoxide dismutase, THLE: Tonic hindlimb extension

Anticonvulsant effect of nifedipine, dizepam and in combination on pentylenetetrazol induced experimental models of epilepsy on albino rats

Background: In many patients, the presently available antiepileptic drugs such as phenobarbital, phenytoin, benzodiazepines, sodium valproate, etc., are unable to control seizures efficiently and the problem of adverse effects has also not been circumvented completely and approximately 30% of the patients continue to have seizures with current antiepileptic drugs therapy. Hence, search should continue to develop newer, more effective, and safer neuro-protective agents for treatment of epilepsy. Aim of the study was to investigate the activity of nifedipine, the dihydropyridine calcium channel blocker, diazepam, the benzodiazepine anti- convulsant of established efficacy and their combinations against rat models of pentylenetetrazol (PTZ) induced convulsions. Method: Wister albino rats of either sex, weighing between 150-220gm were used. Rats were divided into 10 groups, in each group n=6 total N=60.Methods: PTZ was administration 30 min after test drug administration. Intraperitoneal injection of PTZ at the dose of 80mg/Kg body weight were administered to the rats to produce chemically-induced seizure. The effect of nifedipine and diazepam were assessed on such seizure model. The onset and duration of clonic convulsion were recorded.Results: The onset time of PTZ-induced clonic convulsion was significantly prolonged with the Nifedipine in the doses of 4mg and 8mg per Kg. in comparison to nifedipine in dose of 2mg per Kg. The interesting observation was that while Diazepam in 1mg/Kg. dose significantly (P<0.05) prolonged the onset time, there was significant decrease (P <0.001) in the onset time of PTZ-induced clonic convulsion with diazepam in doses of 2 and 4mg per Kg. in comparison to Diazepam 1mg per Kg. But the combination of diazepam 2.5 mg and Nifedipine 2.6mg and 5.3mg exhibited significant prolongation of the onset time. Diazepam 1 and 2mg per Kg was found to be equally effective in reduction of convulsion time, while 4mg dose showed more reduction of convulsion time. The combination of diazepam and nifedipine showed no better reduction in the convulsion time and also valproic acid in doses of 135mg. Kg.Conclusions: Nifedipine (3-5mg/Kg) and diazepam (2.5mg/Kg.) combination delayed the onset of convulsion. Diazepam 2mg / Kg. alone was effective in reduction of duration of convulsion. The combination dose having 2.6mg of nifedipine showed comparable protection with valproic acid 135mg per Kg. while the combination having 5.3mg of nifedipine showed significantly better protection.

Anticonvulsant effect of Portulaca oleracea in experimental animal models

Background: Portulaca oleracea , locally known as Leipak-kundo, which belongs to portulacaceae family is an annual succulent prostrate herb with 15-30 cm long stem, fleshy leaves, and flowers. The plant is used for the treatment of gonorrhea, gum and teeth complaints, scurvy and liver diseases. The constituents of the plant are flavonoids, alkaloids, omega-3 fatty acid, and antioxidants. P. oleracea has been reported to possess hypoglycemic, anti-ulcer, muscle relaxant, analgesic, and anti-inflammatory properties. Materials and Methods: The anticonvulsant effect of the aqueous extract of P. oleracea leaves (200, 400, and 600 mg/kg, p.o.) was studied against seizures induced by maximal electroshock (MES) and pentylentetrazol (PTZ) in albino mice. Results: The aqueous extract of P. oleracea leaves decreased the duration of hind limb tonic extension phase and recovery time in MES model. It also decreased the time of onset and duration of clonic convulsion induced by PTZ. The aqueous extract of P. oleracea leaves exhibited significant anticonvulsant effect against MES and PTZ-induced seizures. Conclusion: The aqueous extract of P. oleracea leaves (200, 400, and 600 mg/kg) produced significant anticonvulsant effect against MES and PTZ-induced seizures in mice. The aqueous extract of P. oleracea may be potentiating the GABAergic transmission in the central nervous system.

Effectiveness of a nonpenetrating captive bolt for euthanasia of piglets less than 3 d of age1

The objective of this study was to determine the effectiveness of a nonpenetrating captive bolt (NPCB), the Zephyr-Euthanasia (Zephyr-E), for euthanasia of neonatal piglets<72 h of age using signs of insensibility and death, as well as postmortem assessment of traumatic brain injury (TBI). The Zephyr-E was used by 10 stock people to euthanize 100 low viability neonatal piglets from 3 commercial farrowing units and 1 research farm. Brainstem reflexes, convulsions, and heartbeat were used to assess insensibility, time of brain death, and cardiac arrest after Zephyr-E application. Hemorrhage severity and skull fracture displacement (FD) were quantified from computed tomography scans (n=10), macroscopic scoring was used to assess brain hemorrhage and skull fracture (SK) severity (n=100), and microscopic scoring was used to assess subdural (SDH) and parenchymal (PH) hemorrhage within specific brain regions that are responsible for consciousness and vital function (n=10). All 100 piglets were rendered immediately insensible without return to sensibility. On average, clonic convulsions (CC) ceased in 101 s (±7.4 SE), brain death was achieved in 229 s (±9.18 SE), and cardiac arrest occurred in 420 s (±13.57 SE). Time of cardiac arrest differed significantly among stock people when either body weight (BW: P=0.0053) or body mass index (BMI: P=0.0059) was used as a covariate. The BMI was inversely related to the duration of CC (P=0.0227). Moderate to severe hemorrhage severity was reported in 9 of 10 piglets. There was no relationship between FD and BW (P=0.8408) or BMI (P=0.6439). Macroscopic analyses indicated moderate to severe hemorrhage and SK in all piglets. No differences were found among brain sections for SDH (P=0.2302); PH was greater in the cerebral cortex than in the midbrain and brainstem (P=0.0328). The Zephyr-E NPCB reliably caused immediate, sustained insensibility followed by death in neonatal piglets. Postmortem assessment confirmed that application of the Zephyr-E caused widespread, irreversible brain damage.

Effect of artesunate on maximal electroshock and pentylenetetrazole-induced seizures in albino mice

Artemisinin-based combination therapies are highly efficacious, and they are now listed as first-line therapies for uncomplicated malaria in most countries where malaria is endemic. Neurotoxicity of artemisinins is a growing concern. However, no studies have reported its antiepileptic or epileptogenesis potential, hence the present study was undertaken to explore the activity of artesunate in experimentally induced seizures in rodent models. Artesunate at doses 36.4 and 72.8 mg/kg respectively significantly reduced the duration of the hind limb extensions (3.033±1.493 and 2.033±1.383, respectively) when compared to the control (P<0.0001) in the maximal electroshock-induced seizure model. However, no significant decrease was noted in the duration of clonic convulsions in a pentylenetetrazole-induced seizure model indicating lack of activity in petit mal epilepsy. The results of the present study indicate that artesunate at both the doses employed showed a significant anticonvulsant activity in the maximum electroshock-induced seizure model suggesting its potential utility in the management of generalized tonic-clonic seizures and partial seizures. Further studies regarding its mechanism of action are warranted. Key words: Anticonvulsant, artesunate, neurotoxicity, pentylene tetrazole-induced seizures and maximum electroshockinduced seizures

Effect of Ethanolic Extract of Indigofera tinctoria on Chemically-Induced Seizures and Brain GABA Levels in Albino Rats.

Indigofera tinctoria Linn. of Fabaceae family is claimed to be useful to control epileptic seizures in the Indian system of folkore medicine. This study was designed to evaluate tinctoria and to verify the claim. Seizures were induced in male albino rats with pentylenetetrazole (PTZ). The test group animals were administered ethanolic extract of Indigofera tinctoria (EEIT) orally. The time of onset and duration of clonic convulsions were recorded. Maximal electroshock seizures (MES) were induced in animals. The duration of hind limb tonic extension (HLTE) was recorded. GABA levels and GABA transaminase activity in brain were estimated. In PTZ model, EEIT significantly (P< 0.01, P< 0.001) delayed the onset of convulsions and reduced the duration of seizures in a dose dependent manner. A significant (P< 0.05) reduction in the duration of HLTE at higher doses of EEIT was observed in MES model. Increase in brain GABA levels was observed on treatment with EEIT at 500 and 1000 mg/kg doses, suggested that the plant may be acting by facilitating GABAergic transmission. A significant reduction (P< 0.05) in the activity of brain GABA transaminase was observed at higher doses. No neurotoxic signs were observed with rotarod test, pentobarbital induced sleeping time, locomotor activity and haloperidol-induced catalepsy. The ethanolic extract of tinctoria was found to be useful to control and treat the variety of seizures.

Effect of cyclooxygenase inhibitors on pentylenetetrazol (PTZ)-induced convulsions: Possible mechanism of action

Cyclooxygenase (COX) is reported to play a significant role in neurodegenerative and neuropsychiatric disorders, and may play a significant role in the pathogenesis of epilepsy. Various neurotransmitter abnormalities, especially of GABA and glutamate, have been reported to play a key role in the pathophysiology of epilepsy. The objective of the present study was to elucidate the effect of cyclooxygenase inhibitors on pentylenetetrazol (PTZ)-induced (80 mg/kg) convulsions in mice with possible mechanism of action. Various COX-inhibitors were administered 45 min prior to the PTZ administration. Onset, duration of clonic convulsions and percentage mortality/recovery were recorded. Pretreatment with COX-inhibitors aspirin (10 and 20 mg/kg, p.o.), naproxen (7 and 14 mg/kg, p.o.), nimesulide (1–5 mg/kg, p.o.) or rofecoxib (1–4 mg/kg, p.o.) dose-dependently showed protection against PTZ-induced convulsions. COX-2 inhibitors were more effective as compared to non-selective COX-inhibitors. Rofecoxib (1 mg/kg) or nimesulide (1 mg/kg) also enhanced the sub-protective effect of diazepam or muscimol showing GABAergic modulation of COX-2 inhibitors. COX-2 inhibitors also antagonized the effect of flumazenil (4 mg/kg)- against PTZ-induced convulsions further confirming the GABAergic mechanism. In conclusion, the results of the present study strongly suggest the possible role of cyclooxygenase isoenzymes in the pathophysiology of epilepsy and the use of COX-inhibitors as an adjuvant therapy in the treatment of epilepsy.