Seizure Latency Research Articles

Anticonvulsant effect of Marsilea quadrifolia Linn. on pentylenetetrazole induced seizure: A behavioral and EEG study in rats

Ethnopharmacological relevanceMarsilea quadrifolia Linn (MQ) extract has been used traditionally as sedative and antiepileptic drug in India. Aim of this studyTo investigate the anticonvulsive potential of MQ extracts by using behavior and electroencephalographic (EEG) analysis on pentylenetetrazole (PTZ) induced seizure model in rats. Materials and methodsFor anticonvulsant effect, 60minutes after administration of MQ, behavior and EEG were analyzed during PTZ (60mg/kg) induced seizures. Changes of EEG power, latency of onset of seizure, seizure severity score, and duration of epileptic seizure were determined. ResultsBoth the water and ethanol extract of MQ increased the latency of seizure but also decreased duration of epileptic seizure and seizure severity score. This reduction of seizure severity was also observed in EEG recording and EEG power analysis. The effectiveness of MQ ethanol extract is better than MQ water extract. ConclusionBoth water and ethanol extract of MQ were effective in reducing the severity of behavioral and EEG seizures induced by PTZ in rats. This study justifies the traditional use of this plant in epilepsy.

EEG-Langzeit-Monitoring - Indikationen und Limitationen im prächirurgischen Monitoring

Epilepsy may be difficult to diagnose at first. Video-EEG Monitoring has two main indications: to assure or reject the diagnosis of epilepsy or to localize the seizure onset zone. Interictal epileptiform discharges (IEDs) are essential in classifying epilepsies. However, knowledge on the latency of IEDs is incomplete. The aim of this study was to assess the latency of IEDs and seizures in long-term EEG recordings of patients with epilepsy and therefore shed some light on the limitations of Video-EEG recordings. We analyzed the latency of IEDs and seizures from video-EEGs of 101.5 ± 62.7 hours (median ± SD) duration in 210 consecutive patients (94 male; age 38.6 ± 13.9 years) with active (median 3.5 seizures/month) epilepsy (176 structural-metabolic, 25 genetic, epilepsy duration 16.4 ± 13.7 years). Variables were age, duration of epilepsy, frequency of seizures and medication, the sleep state with IEDs, and their relation to seizures. Findings: Median spike latency was 9.3 ± 23.9 hours (within 20 min, 30 min, 24, 48, and 72 hours in 7.3%, 9.7%, 74.5%, 87.9%, and 98.2% respectively). Frequency of seizures, number of AEDs, etiology, age of onset or duration of epilepsy, and epilepsy syndrome did not correlate with spike latency. Of ninety patients with temporal lobe epilepsy IEDs were present in 95.6%. We did not find IEDs in 21.4% of long-term recorded patients, despite seizures in half of them. In other words, 21 patients with a seizure had no IED. Conclusion: Long-term EEG recordings of 72h in almost all cases should be sufficient to determine the presence of IEDs in patients with unclear paroxysmal events. Still, one in five patients will not have any IEDs even with EEG of long duration. Since IEDs are not uncommon in nonepileptic events and since one in 10 will not have seizures or IEDs, longer lasting EEGs or video records of habitual events should be mandatory in critical patients to minimize false negative studies.

Increases in seizure latencies induced by subcutaneous docosahexaenoic acid are lost at higher doses

Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid (PUFA) which has been found to have anticonvulsant properties. Our group has previously reported in a pilot study that the acute administration of subcutaneous (s.c.) DHA increases seizure latencies in the maximal pentylenetetrazole (PTZ) seizure test, however it loses its effect at higher doses. The purpose of the present experiments was (1) to confirm that DHA loses its effect at higher doses, (2) to correlate the anticonvulsant properties of DHA with DHA levels in the different lipid pools of serum and (3) to evaluate whether an anticonvulsant dose of DHA resulted in an increase in DHA release from the brain phospholipids following induction of seizure. In the first experiment, male Wistar rats were injected s.c. with 200, 300, 400 or 600 mg/kg of DHA, or 400mg/kg oleic acid (OA, isocaloric control), and seizure tested with the maximal PTZ test 1h post injection (Experiment 1). In a second experiment, subjects received either: (1) an effective dose of DHA (400mg/kg), (2) a higher, non-effective dose (600 mg/kg; based on the findings of Experiment 1), or (3) OA (400mg/kg). Subjects were sacrificed 1h post injection and blood was collected for fatty acid analysis (Experiment 2). In the third experiment, subjects were injected with either the effective dose of DHA (400mg/kg) or OA (400mg/kg). One hour post lipid injection, animals received either PTZ or saline, and animals were euthanized via microwave fixation. Brain were extracted and unesterified fatty acid concentrations were measured (Experiment 3). Experiment 1 confirmed that DHA loses its effects at higher doses in the maximal PTZ test. The 400mg/kg dose was maximally effective but effects were lost at 600 mg/kg. Experiment 2 showed that only the unesterified DHA pool in serum was statistically increased by an acute injection of s.c. DHA (P<0.05, as compared to OA), whereas esterified DHA pools were unchanged (P>0.05). Curiously, unesterified DHA levels were similar in both the 400mg/kg and 600 mg/kg dosage groups. Experiment 3 showed that an anticonvulsant dose of DHA (400mg/kg) did not increase DHA release from brain phospholipids following seizure induction (P>0.05). In conclusion, DHA has anticonvulsant properties when injected s.c., but these properties are lost at higher doses. The anticonvulsant effects of DHA are accompanied by increased levels of unesterified DHA in the serum, but not in increased DHA release from brain phospholipids.

Seizure susceptibility and electroencephalogram power spectra alterations at various phases of the lipopolysaccharide-induced hypothermic response in biotelemetered rats

The neuronal excitability has been evaluated at various phases of lipopolysaccharide (LPS; E. coli O111:B4, 250 μg/kg, ip)-induced hypothermia including the initial phase, the plateau (including the nadir) and the end of the response in biotelemetered adult Wistar rats. The latency of pentylenetetrazole-induced seizures (60 mg/kg, ip) was lower at the initial phase, but a clear anticonvulsive activity was observed at the end of the hypothermic response. Seizure parameters did not change at the nadir. There was no electroencephalogram (EEG) spike-wave activity generation at either phase of the LPS-induced hypothermia. Meanwhile, the power of the 12-32 Hz beta band of the EEG spectra increased at the initial phase. This increment persisted at the plateau where there was also a decrease in the 1-4 Hz delta power. The data indicate that spike-wave activity is not facilitated during LPS-induced hypothermia but, proconvulsant and anticonvulsant activities occur sequentially depending on the phase of the response. The EEG power spectra also change. These effects may not be attributed merely to the reduction of body temperature. Thus, it is possible that pathophysiological mechanisms involved in the development of hypothermia may also be responsible for neuronal excitability changes in rats.

Plausible antioxidant biomechanics and anticonvulsant pharmacological activity of brain-targeted &amp;beta;-carotene nanoparticles

β-Carotene has been established as a known free radical scavenger with chain-breaking antioxidant properties. It has been documented for the treatment of epileptic convulsions at a 200 mg/kg body weight dose. The reported pathogenesis for epileptic convulsions is oxidative stress. Hence, experimental epileptic convulsions via oxidative stress was induced in albino mice epileptic models (maximal electroshock seizure and pentylenetetrazole [PTZ]). A dose concentration equivalent to 2 mg/kg was efficaciously administered in the form of brain-targeted polysorbate-80-coated poly(d,l-lactide-co-glycolide) nanoparticles. The nanoparticles were prepared by solvent evaporation technique and further characterized for their physical parameters, in-vitro release kinetics, and in-vivo brain release via various standard methods. Normal β-carotene nanoparticles (BCNP) and polysorbate-80-coated β-carotene nanoparticles (P-80-BCNP) of 169.8 ± 4.8 nm and 176.3 ± 3.2 nm in size, respectively, were formulated and characterized. Their zeta potential and polydispersity index were subsequently evaluated after 5 months of storage to confirm stability. In vivo activity results showed that a 2 mg unformulated β-carotene dose was ineffective as an anticonvulsant. However, salutary response was reported from BCNP at the same dose, as the hind limb duration decreased significantly in maximal electroshock seizure to 9.30 ± 0.86 seconds, which further decreased with polysorbate-80 coating to 2.10 ± 1.16 seconds as compared to normal control (15.8 ± 1.49 seconds) and placebo control (16.50 ± 1.43 seconds). In the PTZ model, the duration of general tonic–clonic seizures reduced significantly to 2.90 ± 0.98 seconds by the use of BCNP and was further reduced on P-80-BCNP to 1.20 ± 0.20 seconds as compared to PTZ control and PTZ-placebo control (8.09 ± 0.26 seconds). General tonic–clonic seizures latency was increased significantly to 191.0 ± 9.80 seconds in BCNP and was further increased in P-80-BCNP to 231.0 ± 16.30 seconds, as compared to PTZ (120.10 ± 4.50 seconds) and placebo control (120.30 ± 7.4 seconds). The results of this study demonstrate a plausible novel anticonvulsant activity of β-carotene at a low dose of 2 mg/kg, with brain-targeted nanodelivery, thus increasing its bioavailability and stability.

Human Intravenous Immunoglobulins Suppress Seizure Activities and Inhibit the Activation of GFAP-Positive Astrocytes in the Hippocampus of Picrotoxin-Kindled Rats

ABSTRACTWe previously showed that human intravenous immunoglobulin (IVIG) can lower seizure severity and prolong seizure latency in picrotoxin-kindled rats. The aim of this study was to further characterize the effects of IVIG on seizure activity and investigate its influence on astrocytes in the hippocampus of picrotoxin-kindled rats. A rat kindling model was established by peritoneal injections of picrotoxin for 21 days in Wistar rats. Seventy-five rats were equally divided into five groups: picrotoxin, IVIG pretreatment, IVIG post-treatment, normal saline control, and IVIG control. Seizure severity was evaluated according to a six-stage classification. The number and morphology of glial fibrillary acidic protein (GFAP)-positive astrocytes were studied by immunohistochemistry using the anti-GFAP antibody. The cross-sectional area and grayscale of GFAP-positive astrocytes were also determined. In picrotoxin-kindled rats, pretreatment with IVIG appeared to inhibit full kindling rates, and it significantly reduced the number of GFAP-positive cells in the hippocampus (p < .001). IVIG also significantly (p < .001) attenuated the increase in the cross-sectional area and grayscale of GFAP-positive astrocytes in the hippocampus. Our results suggest that by suppressing the expression of GFAP, IVIGs may reduce seizure activity and inhibit the activation of GFAP-positive astrocytes in picrotoxin-kindled rats.

Diverse effects of variant doses of dexamethasone in lithium–pilocarpine induced seizures in rats

Corticosteroids are used in the management of several epileptic aliments; however, their effectiveness in combating seizures remains controversial, with pro- and anti-convulsive effects ascribed. The current study aimed to address the modulatory effect of dexamethasone (DEX) utilizing 3 dose levels (5, 10, and 20 mg/kg body mass of male Wistar rat) in the rat lithium-pilocarpine (Li-PIL) epilepsy model. Li-PIL induced seizures that were associated with neuronal cell loss in the CA3 region, and increased prostaglandin (PG)E(2), tumor necrosis factor (TNF)-α, interleukin (IL)-10, nitric oxide, and neutrophil infiltration in the hippocampus. However, Li-PIL compromised the oxidant-antioxidant balance of the hippocampus. Effective anticonvulsant activity was only observed with 10 mg DEX/kg body mass, which reduced seizure production and incidence, as well as neuronal cell loss in the CA3 region. At this anticonvulsant dose, enhancements in the antioxidant system and IL-10, as well as suppression of altered inflammatory markers were observed. Conversely, doubling the dose showed a tendency to shorten seizure latency, and neither affected seizure incidence nor CA3 neuronal cell loss. These effects were associated with an increase in levels of PGE(2) and TNF-α. The present study found a lack of protection at 5 mg DEX/kg body mass, an anticonvulsant effect at 10 mg/kg, and a loss of protection at 20 mg/kg in the Li-PIL epilepsy model, which indicates that there is an optimal dose of DEX for preventing the induction of seizures.

Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability

Eugenol (EUG, 4-allyl-2-methoxyphenol), the main component of essential oil extracted from cloves, has various uses in medicine because of its potential to modulate neuronal excitability. However, its effects on the ionic mechanisms remains incompletely understood. We aimed to investigate EUG's effects on neuronal ionic currents and excitability, especially on voltage-gated ion currents, and to verify the effects on a hyperexcitability-temporal lobe seizure model. With the aid of patch-clamp technology, we first investigated the effects of EUG on ionic currents in NG108-15 neuronal cells differentiated with cyclic AMP. We then used modified Pinsky-Rinzel simulation modeling to evaluate its effects on spontaneous action potentials (APs). Finally, we investigated its effects on pilocarpine-induced seizures in rats. EUG depressed the transient and late components of I(Na) in the neurons. It not only increased the degree of I(Na) inactivation, but specifically suppressed the non-inactivating I(Na) (I(Na(NI))). Its inhibition of I (Na(NI)) was reversed by tefluthrin. In addition, EUG diminished L-type Ca(2+) current and delayed rectifier K(+) current only at higher concentrations. EUG's effects on APs frequency reduction was verified by the simulation modeling. In pilocarpine-induced seizures, the EUG-treated rats showed no shorter seizure latency but a lower seizure severity and mortality than the control rats. The EUG's effect on seizure severity was occluded by the I(Na(NI)) antagonist riluzole. The synergistic blocking effects of I (Na) and I(Na(NI)) contributes to the main mechanism through which EUG affects the firing of neuronal APs and modulate neuronal hyperexcitability such as pilocarpine-induced temporal lobe seizures.

Creatine reduces oxidative stress markers but does not protect against seizure susceptibility after severe traumatic brain injury

Achievements made over the last years have highlighted the important role of creatine in health and disease. However, its effects on hyperexcitable circuit and oxidative damage induced by traumatic brain injury (TBI) are not well understood. In the present study we revealed that severe TBI elicited by fluid percussion brain injury induced oxidative damage characterized by protein carbonylation, thiobarbituric acid reactive species (TBARS) increase and Na(+),K(+)-ATPase activity inhibition 4 and 8 days after neuronal injury. Statistical analysis showed that after TBI creatine supplementation (300 mg/kg, p.o.) decreased the levels of protein carbonyl and TBARS but did not protect against TBI-induced Na(+),K(+)-ATPase activity inhibition. Electroencephalography (EEG) analysis revealed that the injection of a subconvulsant dose of PTZ (35 mg/kg, i.p.), 4 but not 8 days after neuronal injury, decreased latency for the first clonic seizures and increased the time of spent generalized tonic-clonic seizures compared with the sham group. In addition, creatine supplementation had no effect on convulsive parameters induced by a subconvulsant dose of PTZ. Current experiments provide evidence that lipid and protein oxidation represents a separate pathway in the early post-traumatic seizures susceptibility. Furthermore, the lack of consistent anticonvulsant effect exerted by creatine in this early phase suggests that its apparent antioxidant effect does not protect against excitatory input generation induced by TBI.

Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice

The aim of this study was to evaluate the anti-convulsant effects of magnolol (6, 6', 7, 12-tetramethoxy-2, 2'-dimethyl-1-β-berbaman, C18H18O2) and the mechanisms involved. Mice were treated with magnolol (20, 40 and 80 mg·kg(-1)) 30 min before injection with pentylenetetrazol (PTZ, 60 mg·kg(-1), i.p.). The anti-seizure effects of magnolol were analysed using seizure models of behaviour, EEG and in vitro electrophysiology and c-Fos expression in the hippocampus and cortex. Magnolol at doses of 40 and 80 mg·kg(-1) significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with those of the vehicle-treated animals. EEG recordings showed that magnolol (40 and 80 mg·kg(-1)) prolonged the latency of seizure onset and decreased the number of seizure spikes. The anti-epileptic effect of magnolol was reversed by the GABA(A)/benzodiazepine receptor antagonist flumazenil. Pretreatment with flumazenil decreased the effects of magnolol on prolongation of seizure latency and decline of seizure stage. In a Mg(2+)-free model of epileptiform activity, using multi-electrode array recordings in mouse hippocampal slices, magnolol decreased spontaneous epileptiform discharges. Magnolol also significantly decreased seizure-induced Fos immunoreactivity in the piriform cortex, dentate gyrus and hippocampal area CA1. These effects were attenuated by pretreatment with flumazenil. These findings indicate that the inhibitory effects of magnolol on epileptiform activity were mediated by the GABA(A) /benzodiazepine receptor complex.

Aquaporin-4 Reduces Post-Traumatic Seizure Susceptibility by Promoting Astrocytic Glial Scar Formation in Mice

Seizures are important neurological complications after traumatic brain injury (TBI) and are reported for up to 50% of patients with TBI. Despite several studies, no drug strategy has been able to alter the biological events leading to epileptogenesis. The glial water channel, aquaporin-4 (AQP4), was shown to facilitate cytotoxic cell swelling in ischemia and glial scar formation after stab wound injury. In this study, we examined post-traumatic seizure susceptibility of AQP4-deficient mice (AQP4-/-) after injection of pentylenetetrazole (PTZ) 1 month after controlled cortical impact (CCI) and compared them to wild-type sham injury controls. After PTZ injection, AQP4-/- mice demonstrated dramatically shortened seizure latency (120 ± 40 vs. 300 ± 70 sec; p < 0.001) and increased seizure severity (grade 7.5 ± 0.4 vs. 5.8 ± 0.4; p < 0.001) compared to their wild-type counterparts. Morphometric analysis demonstrated a significant 2-fold reduction in astrocytosis, with a concomitant increase in microgliosis in injured AQP4-null mice compared to their injured wild-type counterparts (44 ± 2 vs. 24 ± 3 cells per high power field [cells/hpf], respectively; p < 0.0001). Minocycline, an inhibitor of microglia, reversed the post-TBI epilepsy phenotype of AQP4-null mice. After minocycline treatment, AQP4-/- mice demonstrated similar latency of seizures evoked by PTZ (723 ± 35 vs. 696 ± 38 sec; p > 0.05) and severity of seizures evoked by PTZ (grade 4.0 ± 0.5 vs. 3.81 ± 0.30; p > 0.05) compared to wild-type counterparts. Immunohistochemical analysis demonstrated decreased immunostaining of microglia to levels comparable to wild-type (12 ± 2 vs. 11 ± 4 cells/hpf, respectively; p > 0.05). Taken together, these results suggest a protective role of AQP4 in post-traumatic seizure susceptibility by promoting astrogliosis, formation of a glial scar, and preventing microgliosis.

Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice

The present study shows interactive effects of pentoxifylline (PTX) as a phosphodiesterase (PDE) inhibitor, H-89 as a protein kinase A (PKA) inhibitor and bucladesine (db-cAMP) as a cAMP agonist on pentylenetetrazol (PTZ)-induced seizure in mice. Different doses of pentoxifylline (25, 50, 100 mg/kg), bucladesine (50, 100, 300 nM/mouse), and H-89 (0.05, 0.1, 0.2 mg/100g) were administered intraperitoneally (i.p.), 30 min before intravenous (i.v.) infusion of PTZ (0.5% w/v). In combination groups, the first and second components were injected 45 and 30 min before PTZ infusion. In all groups, the control animals received an appropriate volume of vehicle. Single administration of PTX had no significant effect on both seizure latency and threshold. Bucladesine significantly decreased seizure latency and threshold only at a high concentration (300 nM/mouse). Intraperitoneal administration of H-89 (0.2 mg/100g) significantly increased seizure latency and threshold in PTZ-treated animals. All applied doses of bucladesine in combination with PTX (50 mg/kg) caused a significant reduction in seizure latency. Pretreatment of animals with PTX (50 and 100 mg/kg) attenuated the anticonvulsant effect of H-89 (0.2 mg/100g) in PTZ-exposed animals. H-89 (0.05, 0.2 mg/100g) prevented the epileptogenic activity of bucladesine (300 nM) with significant increase of seizure latency and seizure threshold. In conclusion, we showed that seizure activities were affected by pentoxifylline, H-89 and bucladesine via interactions with intracellular cAMP and cGMP signaling pathways, cyclic nucleotide-dependent protein kinases, and related neurotransmitters.

Strain differences in seizure-induced cell death following pilocarpine-induced status epilepticus

Mouse strains differ from one another in their susceptibility to seizure-induced excitotoxic cell death. Previously, we have demonstrated that mature inbred strains of mice show remarkable genetic differences in susceptibility to the neuropathological consequences of seizures in the kainate model of status epilepticus. At present, while the cellular mechanisms underlying strain-dependent differences in susceptibility remain unclear, some of this variation is assumed to have a genetic basis. However, it remains unclear whether strain differences in susceptibility to seizure-induced cell death observed following kainate administration are observed following systemic administration of other chemoconvulsants. In rodents, the cholinomimetic convulsant pilocarpine is widely used to induce status epilepticus (SE), followed by hippocampal damage and spontaneous recurrent seizures, resembling temporal lobe epilepsy. This model has initially been described in rats, but is increasingly used in mice. We characterized neuronal pathologies after pilocarpine-induced status epilepticus (SE) in eight inbred strains of mice focusing on the hippocampus. A ramping-up dose protocol for pilocarpine was used and behavior was monitored for 4–5h. While we did not observe any significant differences in seizure latency or duration to pilocarpine among the inbred strains, we did observe a significant difference in susceptibility to the neuropathological consequences of pilocarpine-induced SE. Of the eight genetically diverse mouse strains screened for pilocarpine-induced status, BALB/cJ and BALB/cByJ were the only two strains that were resistant to the neuropathological consequences of seizure-induced cell death. Additional studies of these murine strains may be useful for investigating genetic influences on pilocarpine-induced status epilepticus.

Hydroalcoholic extract of Emblica officinalis protects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant, anti-inflammatory, and neuroprotective intervention

Context: Emblica officinalis (Euphorbiaceae), commonly known as amla, is traditionally used for central nervous system (CNS) disorders.Objective: In the present study, the effect of standardized hydroalcoholic extract of E. officinalis fruit (HAEEO), an Indian medicinal plant with potent antioxidant activity, was studied against kainic acid (KA)-induced seizures, cognitive deficits and on markers of oxidative stress.Materials and methods: Rats were administered KA (10 mg/kg, i.p.) and observed for behavioral changes, incidence, and latency of convulsions over 4 h. The rats were thereafter sacrificed for estimation of oxidative stress parameters: thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH). The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was also determined in the rat brain.Results: Pretreatment with HAEEO (500 and 700 mg/kg, i.p.) significantly (P < 0.001) increased the latency of seizures as compared with the vehicle-treated KA group. HAEEO significantly prevented the increase in TBARS levels and ameliorated the fall in GSH. Furthermore, HAEEO dose-dependently attenuated the KA-induced increase in the TNF-α level in the brain. HAEEO also significantly improved the cognitive deficit induced by KA, as evidenced by increased latency in passive avoidance task.Discussion and conclusion: HAEEO at the dose of 700 mg/kg, i.p., was most effective in suppressing KA-induced seizures, cognitive decline, and oxidative stress in the brain. These neuroprotective effects may be due to the antioxidant and anti-inflammatory effects of HAEEO.

The involvement of Na+, K+-ATPase activity and free radical generation in the susceptibility to pentylenetetrazol-induced seizures after experimental traumatic brain injury

Although the importance of brain trauma as risk factor for the development of epilepsy is well established, the mechanisms of epileptogenesis are not well understood. In the present study, we revealed that the injection of a subthreshold dose of PTZ (30 mg/Kg, i.p.) after 5 weeks of injury induced by Fluid Percussion Brain Injury (FPI) decreased latency for first clonic seizures, increased the time of spent generalized tonic-clonic seizures and electrocorticographic (EEG) wave amplitude. In addition, statistical analysis revealed that N-acetylcysteine (NAC) (100mg/kg) supplementation during 5 weeks after neuronal injury protected against behavioral and electrographical seizure activity elicited by subthreshold dose of PTZ. The supplementation of this antioxidant compound also protected against the Na(+),K(+)-ATPase activity inhibition and concomitant increase in the levels of oxidative stress markers (protein carbonylation and thiobarbituric acid-reactive substances-TBARS) in site and peri-contusional cortical tissue. In summary, the current experiments clearly showed that FPI model induces early posttraumatic seizures and suggest that an alteration in the lipid/protein oxidation, membrane fluidity, and Na(+),K(+)-ATPase activity may be correlated with neuronal excitability, a significant component of the secondary injury cascade that accompanies TBI.

Reliability of Seizure Semiology in Patients With 2 Seizure Foci

To determine whether seizure semiology is reliable in localizing and distinguishing seizures at 2 independent brain foci in the same patient. Two masked reviewers localized seizures from 2 foci by their clinical semiology and intracranial electroencephalograms (EEGs). Epilepsy monitoring unit of referral comprehensive epilepsy program. Seventeen consecutive patients (51 seizures) with sufficient video and intracranial EEG data were identified by reviewing medical records of 366 patients older than 10 years. The primary outcome measures were interobserver agreement between the 2 masked reviewers; the proportion of seizures localized by semiology; the proportion of localized seizures concordant with intracranial EEG localization; and comparison between concordant and nonconcordant seizures in latency of intracranial EEG seizure spread. Interobserver agreement was 41% (κ score, 0.16). Only 30 of 51 seizures (59%) were localized by seizure semiology. The focus localized by semiology was concordant with the location of intracranial EEG seizure onset in 16 of 30 seizures (53%). No significant difference was observed between concordant and nonconcordant seizures in relation to the speed with which the EEG discharge spread from the location of seizure onset to another lobar region (P = .09, Wilcoxon rank sum test). Clinical seizure semiology is not as useful as intracranial EEG in localizing seizure onset in patients with dual seizure foci.

Investigating the Role of Zinc in a Rat Model of Epilepsy

The aim of the present study was to investigate the role of zinc (Zn) in pilocarpine-induced seizures and its interrelation with an antiepileptic drug, namely, valproic acid. The study was carried out on 110 male Wistar albino rats that were divided into the following groups: Group I, control rats that received intraperitoneal (i.p.) saline vehicle; Groups II-V received Zn in a medium dose, Zn in a high dose, valproic acid in a therapeutic dose, as well as a combination of valproic acid with medium dose Zn, respectively, for 3 weeks before saline injection, Group VI received i.p. pilocarpine to induce seizures; Groups VII-XI received Zn in a medium dose, Zn in a high dose, valproic acid in a therapeutic dose, a combination of therapeutic dose of valproic acid with medium dose Zn, as well as a combination of subeffective dose of valproic acid with medium dose of Zn, respectively, for 3 weeks before pilocarpine injection. The seizure's latency and severity for each rat was recorded. Blood and brain hippocampal samples were collected for determination of serum neuron specific enolase (NSE), hippocampal Zn, interleukin-1 beta concentrations as well as hippocampal superoxide dismutase and caspase-3 activities. The results of the current study demonstrated that pretreatment with high dose of Zn exacerbated pilocarpine-induced seizures. Whereas, a medium dose of Zn and valproic acid either alone or in combination reduced the severity of pilocarpine-induced limbic seizures and increased the latency to attain the forelimb clonus. Also both drugs, either alone or in combination, ameliorated all studied biochemical parameters with the exception of hippocampal Zn concentration, which was only significantly increased by pretreatment with Zn, either alone or in combination with valproic acid. The present study highlights the antiepileptic role that could be played by Zn, when given in appropriate doses.

Changes in seizure susceptibility after successive treatments of mice with tryptophol and ethanol.

Changes in leptazol (pentetrazol) seizure susceptibility after successive treatments of mice with tryptophol, a neutral metabolite of indoleamine, in combination with ethanol have been examined. Mice treated with tryptophol plus ethanol became highly susceptible to convulsion. There was little or no difference in seizure susceptibility in mice treated with tryptophol or ethanol alone, compared with the corresponding controls. In the mice treated with tryptophol plus ethanol, a much higher brain tryptophol level was observed, compared with that in mice treated with tryptophol alone. There appeared to be a good correlation between the reduction of the length of the seizure latency time and the time for which the brains were exposed to high levels of tryptophol. These results suggest that elevation of the levels of neutral indoleamine metabolites in the brain may have resulted in the increase in the seizure susceptibility.

P03-117 - Antiepileptic effects of quinine in the pentylenetetrazole model of seizure

IntroductionQuinine, is an anti-malarial drug that specifically blocks connexin 36 at gap junction channels.ObjectiveQuinine has suppressed ictal epileptiform activity in vitro without decreasing neuronal excitability.AimWe considered the possible anticonvulsant effects of quinine in the pentylenetetrazole (PTZ) model of seizure.MethodsIn five groups, the mice were given quinine at the doses of 20, 30, 40, 50, or 60 mg/kg 30 min before the administration of PTZ (90 mg/kg). Two groups were injected with diazepam, the positive control (0.5, 1 mg/kg) and one group, the control group, was injected with saline + Tween 80 before the administration of PTZ. The onset of a general clonus was used as the endpoint. The general clonus was characterized by forelimb clonus followed by full clonus of the body.ResultsIn the PTZ model, quinine at the dose of 60 mg/kg increased the latency of seizure. However, quinine at 40-60 mg/kg decreased the duration of seizure, dose dependently.ConclusionThe present study provides evidence for anticonvulsant activity of quinine in the generalized clonic seizure of PTZ model. As a result of these finding, we suggest that gap junctions represent an appropriate target for the development of drugs aimed at decreasing epileptiform synchronization and preventing epileptogenesis.

Anticonvulsant and neurotoxicity profile of the rhizome of Smilax china Linn. in mice

Objective:To study the anticonvulsant activity and neurotoxicity of ethanolic extract and ethyl acetate fraction of the rhizome of Smilax china (EESC and EAF, respectively) in mice.Materials and Methods:The anticonvulsant activities of EESC and EAF were studied against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice and neurotoxicity was determined using rotarod test.Results:The duration of hindleg extension in MES test was reduced significantly (P < 0.001) by EESC at a dose level of 400 mg/kg and EAF at both higher dose levels (200 and 400 mg/kg). In PTZ model, the seizure latency was prolonged by all the test groups.Conclusion:The EESC and EAF may help to control petit mal and grand mal seizures.