Generalized Tonic-clonic Seizures Latency Research Articles

Neuroprotective effects of the fractions of Ocimum basilicum in seizures induced by pentylenetetrazole in mice.

Neuroprotective and antioxidant effects of Ocimum basilicum (O. basilicum) against pentylenetetrazole (PTZ)-induced seizures were investigated. Mice were divided as follows: (Group 1) Control, (Group 2) PTZ, (Groups 3-5) 50,100 and 200 mg/kg hydro-ethanolic (HE) extract, and (Groups 6-8) 200 mg/kg ethyl-acetate (EAF), N-hexane (NHF) and water (WF) fractions. Minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) latencies were measured. Biochemical and histological studies were done. MCS and GTCS latency in HE groups were longer than the PTZ group (p<0.05 to p<0.001). EAF and NHF prolonged the onset of MCS and GTCS (p<0.001). PTZ increased malondialdehyde (MDA) and dark neuron (DN) production while decreased thiol, catalase (CAT) and superoxide dismutase (SOD) (p<0.05 to p<0.001). Pre-treatment by HE and all fractions of the plant attenuated MDA and DN while increased thiol, CAT and SOD (p<0.01 to p<0.001). EAF and NHF had anticonvulsant properties. The extract and fractions protected the brain from PTZ-induced oxidative damages and showed neuroprotective effects.

Effects of Hydro-ethanolic Extract of Tanacetum parthenium and its N-Butanol and Aqueous Fractions on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice

Background: Epileptic seizures affect the life of noticeable number of people in all over the world. Tanacetum parthenium (TP) is used in traditional medicine. We studied the effects of hydro- ethanolic extract of TP and its n-butanol and aqueous fractions on brain oxidative damage in pentylenetetrazole (PTZ)-induced seizures in mice. Methods: Male mice were divided into: (1) Control; (2) PTZ (100 mg/kg, i.p.); (3-5) hydro-ethanolic extract of TP (50, 100 and 200 mg/kg); (6) n-butanol (NBut) (100 mg/kg) and (7) aqueous (Aq) (100 mg/kg) fractions. Extracts were injected (i.p.) for 3 days and 30 min before PTZ. Latencies in onset of Minimal Clonic Seizures (MCS) and Generalized Tonic-Clonic Seizures (GTCS) as well as biochemical indicators were evaluated. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Results: demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress. Results: Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group. Conclusion: Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Suvorexant, a Dual Orexin Receptor Antagonist, Protected Seizure through Interaction with GABAA and Glutamate Receptors.

Orexin can increase neuronal excitability and induce epileptic activity. In this study, the effects of suvorexant (orexin receptor antagonist) on pentylenetetrazol (PTZ) and maximal electroshock (MES)-induced seizure were investigated. Mice were divided into 5 groups of six animals each including normal saline (10 mL/kg), diazepam (2 mg/kg), and suvorexant (50, 100 and 200 mg/kg) groups. In PTZ test, the latency to first minimal clonic seizure (MCS), latency to the first generalized tonic–clonic seizures (GTCS), total duration of seizure and also protection against mortality were evaluated. In MES, the hind limb tonic extension (HLTE) and the protection against mortality were recorded. In order to evaluate the role of GABAA in anticonvulsant effect of suvorexant, flumazenil was used and to investigate the role of glutamate, the protein levels of AMPAR and NMDAR were measured in hippocampus by western blotting. In PTZ model, suvorexant (200mg/kg) increased MCS and GTCS latencies. Suvorexant (100 and 200 mg/kg) decreased total duration of seizure compared to control group. In PTZ model, flumazenil inhibited the prolongation of seizure latency induced by suvorexant. In MES, the HLTE was decreased by suvorexant (100 and 200 mg/kg) and suvorexant was protected against mortality by 83.3%. Moreover, the protein levels of NMDAR and AMPAR were decreased by suvorexant. Suvorexant exerted anticonvulsant activity and in addition to its inhibitory effect on orexin receptors, this effect may be mediated, at least partly, through interaction with GABAA and glutamate receptors.

L-Homocarnosine, l-carnosine, and anserine attenuate brain oxidative damage in a pentylenetetrazole-induced epilepsy model of ovariectomized rats.

In this study, we investigated the protective effect of l-homocarnosine, l-carnosine, and anserine (HCA) on seizure-induced brain injuries. We evaluated the protective effect of HCA on brain oxidative damage in a pentylenetetrazole (PTZ)-induced epilepsy model using ovariectomized (OVX) rats. The experimental groups were as follows: group I, sham; group II, sham + PTZ; group III, sham + HCA + PTZ; group IV, OVX; group V, OVZ + PTZ; and group VI, OVX + HCA + PTZ. We determined the levels of lipid peroxidation, glutathione peroxidase (Gpx), reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and thiol in brain hippocampal and cortical tissue. The biochemical markers were significantly altered in the brain tissue of OVX rats. HCA supplementation significantly reduced lipid peroxidation and increased GSH, Gpx, SOD, catalase, and thiol levels in PTZ-treated OVX rats. Rats with an ovariectomy showed a significant protective effect against PTZ through elevation of the latency of generalized tonic-clonic seizures (GTCS). HCA substantially increased minimal clonic seizure and GTCS latency in the OVX-PTZ and sham-PTZ groups. In summary, our experimental data indicate that combined supplementation of HCA substantially increased anticonvulsant activity. Moreover, combined HCA supplementation reduced oxidative damage by decreasing lipid peroxidation and increasing antioxidant levels in the brain of a PTZ-induced seizure rodent model.

The Effects of Aqueous Extract of Apium Graveolens on Brain Tissues Oxidative Damage in Pentylenetetrazole-induced Seizures Model in Rat

Introduction: An important role for oxidative stress both as a consequence and as a cause of epileptic seizures has been suggested. Regarding the antioxidant and central nervous system depressant effects of Apium graveolens, the effects of aqueous extract of the plant on the brain tissues oxidative damage in pentylenetetrazole (PTZ)-induced seizures model was investigated. Materials & methods: Male Wistar rats were divided into 5 groups and treated: Control (saline), PTZ and three doses of the Apium graveolens extract (100, 500 and 1000 mg/kg) before PTZ. Latency to the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) were recorded. The brain tissues were then removed for biochemical measurements. Results: MCS and GTCS latencies in extract treated groups were significantly higher than that of PTZ group (P < 0.05-P< 0.01). The malondialdehyde (MDA) levels in the brain tissues of PTZ group were significantly higher than that of control animals (P < 0.01-P< 0.001). Pretreatment with the extract resulted in a significant reduction in the MDA levels (P < 0.05-P< 0.001). Following PTZ administration, a significant reduction in total thiol content was observed in the brain tissues (P < 0.05- P < 0.01). Pretreatment with the extract was not effective to prevent from the lowering effects of PTZ- induced seizures on total thiol concentrations in the brain tissues. Conclusion: The present study showed that aqueous extract of Apium graveolens aerial parts possess anticonvulsant activity. This activity is accompanied by an antioxidant effect in the brain.

Anticonvulsant effect of Satureja hortensis aerial parts extracts in mice.

Regarding the anticonvulsant effects of Satureja hortensis (S . hortensis) in Avicenna's book: canon of medicine; the present study was undertaken to evaluate the anti- eplileptic effects of S . hortensis aqueous and ethanolic aerial part extracts. Furthermore, the mechanisms of their anticonvulsant activities were also evaluated. Seizure was induced by Pentylentetrazol (PTZ) and MES (maximal electroshock) models. Mice were randomly divided into 8 groups; negative control (normal saline, 10ml/Kg), positive control (diazepam, 2 mg/kg), S. hortensis aqueous and ethanolic extracts (200, 400 and 600 mg/kg). In PTZ test, latency to the first minimal clonic seizure (MCS), latency to the first generalized tonic-clonic seizures (GTCS), the total duration of seizures and protection against mortality were evaluated. In MES test, the stretching length of extremities and protection against mortality were recorded. Aqueous and ethanolic extracts (400 and 600 mg/kg) significantly increased MCS and GTCS latencies in PTZ model. Three doses of the extracts decreased the total duration of seizure. These extracts did not show any protective effects on seizure induced by MES model. In PTZ model, flumazenil, an antagonist of benzodiazepine (BZD) site in the GABAA-BZD receptor complex and 7- nitroindazole (7- NI), a selective nNOS (neuronal nitric oxide synthase) inhibitor, reduced the prolongation of seizure latency. S. hortensis showed anticonvulsant activity in PTZ model and this effect may be mediated, at least partly, through interacting with nitric oxide and GABAA-BZD receptor complex.

The role for nitric oxide on the effects of hydroalcoholic extract of Achillea wilhelmsii on seizure.

Objective : Nitric oxide (NO) plays an important role both as a consequence and as a cause of epileptic seizures. Regarding the central nervous system depressant effects of Achillea wilhelmsii (A. wilhelmsii), as well the effects of the plant on NO, this study was aimed to elucidate the possible role for nitric oxide on the effects of hydroalcoholic extract of A. wilhelmsii on pentylenetetrazole (PTZ)-induced seizures. Fifty-six male Wistar rats were divided into 7 groups (n=8 in each group) and treated with (1) normal saline, (2) normal saline before pentylenetetrazole (PTZ, 90 mg/kg), (3-7) A. wilhelmsii extract (100, 200, 400, 800, and 1200 mg/kg) before PTZ. Latency to first minimal colonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) as well as the mortality rate were recorded. The brain tissues were then removed for biochemical measurements. Fisher's exact probability test as well as analysis of variance (ANOVA), followed by Tukey's test were used for statistical evaluation. Treatment with 100- 1200 mg/kg of the extract did not affect MCS latencies. 400 mg/kg of the extract prolonged GTCS latency (p<0.001), however, the lower and higher doses were not effective. Nitric oxide metabolites concentrations in the hippocampal tissues of the animals treated with 100, 200, and 400 mg/kg of the extract were increased compared with saline (p<0.05-p<0.01). The present study showed that hydroalcoholic extract of A. wilhelmsii affects NO metabolites in brain tissues as well the severity of seizures in PTZ-induced seizure model.

Contribution of estradiol in sex-dependent differences of pentylenetetrazole-induced seizures in rats

In the present study the contribution of estradiol in sex-dependent differences of pentylenetetrazole (PTZ)-induced seizures was investigated in rats. The rats were divided into four groups: 1) sham, 2) ovariectomized (OVX), 3) ovariectomized-estradiol (OVX-Est) and 4) male. The OVX-Est group received estradiol valerate (2 mg/kg; i.m/4 weeks) while, male, sham and OVX groups received vehicle. The animals were injected by PTZ (90 mg/kg). The latencies to minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS), were recorded. Serum 17β-estradiol and testosterone levels were also determined using an Elisa kit. GTCS latency in OVX rats was higher than in sham-operated animals (P < 0.05). MCS and GTCS latency in the male group was significantly higher than in the sham, OVX and OVX-Est groups (P < 0.001 and P < 0.01). There was no significant difference in MCS or GTCS latencies among OVX-Est, sham and OVX groups. Serum 17β-estradiol level in the OVX group was significantly lower than in the sham (P < 0.01) and in the OVX-Est group it was higher than in the sham, OVX and male groups (P < 0.01 and P < 0.001). Serum testosterone level in the male group was significantly higher than in all the other three groups (P < 0.001). It seems that testosterone probably has a more efficient role than estradiol in the gender dependent difference in seizure caused by PTZ in rats.

EFFECT OF BERBERINE ON PENTYLENETETRAZOL-INDUCED SEIZURES IN RATS

Objective: Antiepileptic drugs (AEDs) that are usually used for treatment of epilepsy have substantial side effects and about 30% of patients continue to have seizures with current AEDs therapy. Some herbs which traditionally used in the management of seizures of many rural areas of the developing countries have shown anticonvulsant activity in modern pharmacological bioassays. The aim of the present study was to evaluate the effects of berberine, an alkaloid from Berberis vulgaris, on seizures induced by pentylenetetrazol (PTZ) in rats. Material and Methods: Rats (n=6-7) received berberine (100, 200 and 400 mg/kg, i.p.), diazepam (4mg/kg, i.p. as positive control), and vehicle (saline) and then 30 min later PTZ (110mg/kg, i.p.) were injected . Behavioral responses of the animals to PTZ administration were evaluated using these criteria: latency to first minimal clonic seizure (MCS), incidence of MCS, latency to the first generalized tonic–clonic seizures (GTCS), incidence of GTCS, protection against GTCS and mortality. Results: Intraperitoneal administration of lower doses of berberine (100 and 200 mg/kg) had no significant effects on minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) latencies, while injection of 400 mg/kg caused significant increase in both MCS and GTCS latencies (p<0.05). In this study diazepam, (4 mg/kg) 30 min prior to PTZ, significantly increased GTCS latency. Berberine at tested doses had no protection against mortality following PTZ administration. Conclusion: It can be concluded that berberine at high doses could be a useful protective agent in PTZ-induced epileptic seizures in rats.

The effect of l-arginine and l-NAME on pentylenetetrazole induced seizures in ovariectomized rats, an in vivo study

The role of ovarian hormones and nitric oxide (NO) on seizure and their interaction have been widely investigated. The present study carried out to evaluate the effect of chronic administration of l-arginine ( lA) and l-NAME ( lN) on pentylenetetrazole (PTZ) induced epilepsy in ovariectomized (OVX) and naïve female rats. Fourty-eight female rats were randomly divided into six groups ( n = 8) as follows: (1) sham, (2) ovarectomized (OVX), (3) sham- lA, (4) sham- lN, (5) OVX- lA, and (6) OVX- lN. The animals of sham- lA and OVX- lA received daily injection of 500 mg/kg l-arginine (i.p.) during 4 weeks. Sham- lN and OVX- lN were treated by 10 mg/kg l-NAME (i.p.) daily for 4 weeks. The animals of sham and OVX groups received 1 ml/kg saline (i.p.) instead of l-arginine and l-NAME. The latencies to minimal clonic seizures (MCS) and generalized tonic–clonic seizures (GTCS) after intraperitoneal injection of penetylenetetrazole (PTZ, 90 mg/kg) was recorded and compared between groups. A significant increase in the GTCS, but not MCS, latency was seen in OVX rats in comparison with sham-operated animals. Pretreatment of animals with l-NAME resulted in a significant increase in the GTCS and MCS latencies in sham group while no significant effects were seen in OVX rats. On the contrary, while pretreatment with l-arginine had no effects on MCS and GTCS latencies in sham group, a significant decrease in GTCS latency was observed in OVX rats. It is concluded that ovarian sex hormones affect seizure thresholds induced by PTZ and NO has a role on seizures susceptibility following PTZ administration. This NO effect might be differing in the presence or absence of ovarian hormones, but further investigations need to be done.

Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems

The aim of the present study was to evaluate the effects of safranal, an active constituent of Crocus sativus L. stigmas, on seizures induced by pentylenetetrazol. Intracerebroventricular (i.c.v.) microinjection of safranal (4.84, 9.68 and 24.2 micromol) had no effects on tonic and clonic phases as well as mortality upon seizures induced by PTZ (90mg/kg body wt., i.p.). Peripheral administration of safranal (72.75, 145.5 and 291 mg/kg body wt., i.p.), however, induced a dose-dependent decrease in the incidence of both minimal clonic seizures (MCS) (145.5 mg/kg body wt., p<0.01) and generalized tonic-clonic seizures (GTCS) (145.5 mg/kg body wt., p<0.001) following PTZ administration. Safranal also increased MCS and GTCS latency, significantly. Percent of protection against GTCS was 30%, 100% and 100% and mortality protection percent was 40%, 100% and 100% for the mentioned doses, respectively. Pretreatment with flumazenil (5 nmol, i.c.v.) and naloxone (5.5 nmol, i.c.v. and 2 mg/kg body wt., i.p.), 15 min prior to safranal administration (145.5 mg/kg body wt., i.p.), abolished the protective effect of safranal on MCS. Flumazenil also decreased the effect of safranal on incidence as well as latency of GTCS, significantly. These effects were not, however, significant for naloxone (5.5 nmol, i.c.v. and 2mg/kg body wt., i.p.). Results of this study demonstrated that safranal could exert anticonvulsant activity in the PTZ model and this effect may be mediated, at least partly, through GABA(A)-benzodiazepine receptor complex.

Differential effects of NMDA antagonists microinjections into the nucleus reticularis pontis caudalis on seizures induced by pentylenetetrazol in the rat

It has been shown that NMDA antagonists block the tonic but not the clonic component of seizures when they are injected in the oral region of the rat pontine reticular formation (PRF). The participation of the caudal PRF in the effects of NMDA antagonists upon the tonic and the clonic components of generalized seizures induced by pentylenetetrazol (PTZ) is unknown. The aim of the present study was to evaluate the effects of unilateral microinjections of competitive and non-competitive NMDA antagonists, 2-amino-7-phosphonoheptanoic acid (AP-7) and dizocilpine (MK-801), respectively, into the nucleus reticularis pontis caudalis of the rat PRF upon seizures induced by PTZ (70 mg/kg i.p.). MK-801 induced a dose-related decrease both in the incidence of generalized tonic–clonic seizures (GTCS) and in the presence of spikes in the EEG. MK-801 also increased GTCS latency. On the contrary, AP-7 did not have effects on GTCS. Interestingly, it induced ipsilateral circling behavior. These results suggest that in the caudal region of the rat PRF only non-competitive NMDA antagonists should block the generation of tonic and clonic components of generalized seizures.