bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Different Anticonvulsant Actions of Tiagabine in Developing Rats
Authors: Haugvicová R. , Škutová M. , Kubová H. , Suchomelová L. , Mareš P. 
Published: August 2005

Summary: Purpose: Our goal was to study the anticonvulsant action of tiagabine (TGB) at different levels of brain maturation in rats. Methods: Wistar rats in five age groups (7, 12, 18, 25, and 90 days old) were injected intraperitoneally with TGB at doses of 0.5–32 mg/kg. Thirty minutes later, motor seizures were induced by the subcutaneous adminstration of pentylenetetrazol (PTZ) in a dose of 100 mg/kg for all of the groups except the 18‐day‐old rat pups, which received a 90‐mg/kg dose. The incidence and latency of two types of motor seizures, minimal clonic and generalized tonic‐clonic seizures (GTCSs), were evaluated, and the seizure severity was scored. The time profile of TGB action at the 8‐mg/kg dose was studied in the 12‐ and 25‐day‐old rats. Results: Minimal clonic seizures were reliably induced in rats 18 days old or older, and the seizures were suppressed by TGB in all of these age groups. Although TGB was very effective against this type of seizure in the 18‐day‐old rats, the efficacy of the drug decreased with the age of the animal. GTCSs were suppressed by TGB in the adult and 25‐day‐old rats, and a U‐shaped dose‐response curve was outlined in these two groups. The 18‐ and 12‐day‐old rat pups exhibited a selective suppression of the tonic phase of GTCSs. A mixture of these two effects was observed in the youngest group. TGB demonstrated a markedly longer action in the 12‐day‐old rats than in the 25‐day‐old rats. Conclusions: TGB exhibits anticonvulsant action against both minimal seizures and GTCSs. Ontogenetic development of these two actions is markedly different.
Subacute Electrical Stimulation of the Hippocampus Blocks Intractable Temporal Lobe Seizures and Paroxysmal EEG Activities
Authors: Velasco Marcos , Velasco Francisco , Velasco Ana Luisa , Boleaga Bernardo , Jimenez Fiacro , Brito Francisco , Marquez Irma 
Published: August 2005

Summary: Purpose: To investigate the clinical, electroen‐cephalographic (EEG), and histopathologic effects of subacute electrical stimulation of the hippocampal formation or gyms (SAHCS) on 10 patients with intractable temporal lobe seizures. Methods: Bilateral, depth, hippocampal or unilateral, subdural, basotemporal electrodes were implanted in all 10 patients for a topographic diagnosis of the site and extent of the epileptic focus before a temporal lobectomy. In all patients, anti‐epileptic drugs (AEDs) were discontinued from 48 to 72 h before a program of continuous SAHCS, which was performed for 2–3 weeks. Stimulation parameters were biphasic Lilly wave pulses, 130/s in frequency, 450 μs in duration, and 200–400 μA in amplitude. The stimuli were delivered 23 of every 24 h for the 2–3–week SAHCS period. The effects of SAHCS on the number of clinical seizures per day and the percentage of interictal EEG spikes per 10–second samples of maximal paroxysmal activity at the epileptic focus were determined daily during the 16 days of SAHCS. At the completion of this program, patients underwent an en bloc temporal lobectomy, and the histopathologic effects of SAHCS on the stimulated tissue were analyzed by means of light‐microscopy studies. Results: In seven patients whose stimulation electrode contacts were placed within the hippocampal formation or gyrus and who experienced no interruption in the stimulation program, SAHCS abolished clinical seizures and significantly decreased the number of interictal EEG spikes at the focus after 5–6 days. The most evident and fast responses were found by stimulating either the anterior pes hippocampus close to the amygdala or the anterior parahippocampal gyrus close to the entorhinal cortex. Other surface, hippocampal, and basotemporal EEG signs predicted and accompanied this antiepileptic response. These included an electropositive DC shift and monomorphic delta activity at the medial hippocampal and parahippocampal regions, and a normalization of the background EEG activity and signs of slow‐wave sleep in surface, depth, and subdural regions. In contrast, no evident antiepileptic responses or no responses at all were found in three patients when stimulation was either interrupted or when it was administered outside the hippocampus.Light microscopy analysis of the stimulated hippocampal tissue showed histopathological abnormalities attributable to the depth‐electrode penetration damage or to the pial surface reaction to the subdural, Silastic electrode plate. However, no evident histopathological differences were found between the stimulated and nonstimulated hippocampal tissue. Conclusions: SAHCS appears to be a safe procedure that can suppress temporal lobe epileptogenesis with no additional damage to the stimulated tissue.
The Anticonvulsant SGB‐017 (ADCI) Blocks Voltage‐Gated Sodium Channels in Rat and Human Neurons: Comparison with Carbamazepine
Authors: Sun Lucy , Lin Stephen S. 
Published: August 2005

Summary: Purpose: SGB‐017 (ADCI) is a novel anticonvul‐sant that blocks both voltage‐activated sodium channels and N‐methyl‐d‐aspartate (NMDA)‐receptor‐gated channels. Results by Rogawski et al. suggested that SGB‐017 produces its anticonvulsant action primarily by inhibition of NMDA‐receptor channels. However, SGB‐017 is effective in several animal models of epilepsy that are unresponsive to NMDA antagonists. These results indicate that block of NMDA‐receptor channels is not the only mechanism contributing to its anticonvulsant activity. Thus the effects of SGB‐017 on neu‐ronal sodium channels were investigated. Methods: Whole cell voltage‐clamp techniques were used to record sodium currents in freshly dissociated rat superior cervical ganglion (SCG) and hippocampal neurons and cultured human NT2 neurons. The effects of SGB‐017 on the amplitude of sodium currents, elicited by a depolarizing pulse to 0 mV from different holding potentials, were measured and compared with those of carbamazepine (CBZ). Results: SGB‐017 inhibited sodium currents in rat SCG and hippocampal neurons with a similar potency to CBZ. Like CBZ, the inhibition of sodium channels by SGB‐017 was voltage dependent. Its median inhibitory concentration (IC50) for inhibition of sodium channels at depolarized holding potentials is similar to that for its inhibition of NMDA receptor channels. In human hNT2 neurons, SGB‐017 was more potent than CBZ at inhibiting sodium currents. Conclusions: SGB‐017 produces its anticonvulsant activity by blocking both sodium‐ and NMDA‐receptor channels in a voltage‐ and use‐dependent manner. The combination of these two mechanisms of action makes SGB‐017 an effective AED in several different animal models of epilepsy.
Cyclosporine Induces Epileptiform Activity in an In Vitro Seizure Model
Authors: Wong Michael , Yamada Kelvin A. 
Published: August 2005

Summary: Purpose: Cyclosporine (CSA) toxicity represents a common cause of seizures in transplant patients, but the specific mechanisms by which CSA induces seizures are unknown. Although CSA may promote seizure activity by various metabolic, toxic, vascular, or structural mechanisms, CSA also has been hypothesized to modulate neuronal excitability directly. The objective of this study was to determine if CSA exerts direct epileptogenic actions on neurons in an in vitro seizure model. Methods: Combined hippocampal‐entorhinal cortex slices from juvenile rats were exposed directly to artificial cerebro‐spinal fluid (ACSF) containing either (a) 1.0 mM magnesium sulfate (control), (b) 1.0 mM sodium sulfate (low‐magnesium), or (c) 1.0 mM magnesium sulfate + CSA (1,000–10,000 ng/ml). Spontaneous and evoked extracellular field potentials were recorded simultaneously from the dentate gyrus (DG) and CA3 hippocampal regions. Evoked synaptic responses were elicited by stimulation of the entorhinal cortex/perforant pathway. Results: CSA elicited spontaneous or stimulation‐induced epileptiform activity in the DG or CA3 region of –40% of slices, consisting of brief repetitive “interictal” discharges or prolonged stereotypical “ictal” discharges. Mean latency to epileptiform activity was –100 min after onset of CSA application. The interictal discharges were inhibited by the non‐NMDA antagonist, NBQX. Similar epileptiform activity was observed in low‐magnesium ACSF without CSA. In control ACSF alone, epileptiform activity was not seen, except for rare spontaneous potentials in the DG. Conclusions: Direct effects of CSA on neuronal excitability and synaptic transmission may contribute to seizures seen in clinical CSA neurotoxicity.
The Role of Intracranial Electrode Reevaluation in Epilepsy Patients After Failed Initial Invasive Monitoring
Authors: Siegel Adrian M. , Roberts David W. , Thadani Vijay M. , McInerney James , Jobst Barbara C. , Williamson Peter D. 
Published: August 2005

Summary: Purpose: Intracranial electrode recording often provides localization of the site of seizure onset to allow epilepsy surgery. In patients whose invasive evaluation fails to localize seizure origin, the utility of further invasive monitoring is unknown. This study was undertaken to explore the hypothesis that a second intracranial investigation is selected patients warrants consideration and can lead to successful epilepsy surgery. Methods: A series of 110 consecutive patients with partial epilepsy who had undergone intracranial electrode evaluation (by subdural strip, subdural grid, and/or depth electrodes) between February 1992 and October 1998 was retrospectively analyzed. Of these, failed localization of seizure origin was thought to be due to sampling error in 13 patients. Nine of these 13 patients underwent a second intracranial investigation. Results: Reevaluation with intracranial electrodes resulted in satisfactory seizure‐onset localization in seven of nine patients, and these seven had epilepsy surgery. Three frontal, two temporal, and one occipital resection as well as one multiple subpial transection were performed. Six patients have become seizure free, and one was not significantly improved. The mean follow‐up is 2.8 years. There was no permanent morbidity. Conclusions: In selected patients in whom invasive monitoring fails to identify the site of seizure origin, reinvestigation with intracranial electrodes can achieve localization of the region of seizure onset and allow successful surgical treatment.
Proton Magnetic Resonance Spectroscopic Imaging Studies in Patients with Newly Diagnosed Partial Epilepsy
Authors: Li Li Min , Dubeau François , Andermann Frederick , Arnold Douglas L. 
Published: August 2005

Summary: Purpose: To assess whether the N‐acetyl aspartate (NAA) to creatine ratio (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful treatment of seizures with antiepileptic drugs is sufficient for normalization of NAA/Cr. Patients and Methods: Proton magnetic resonance spectro‐scopic imaging (1H‐MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly diagnosed epilepsy before or soon after starting medication. Six patients had follow‐up 1H‐MRSI examinations 7 months later. Clinical pattern of the seizures and the EEG findings suggested partial seizures in all and TLE in five patients. None of the patients had lesional epilepsy according to magnetic resonance imaging. Results: Initial 1H‐MRSI of the temporal lobes showed significantly low NAA/Cr values in five of eight patients. Five of six patients who had follow‐up 1H‐MRSI were seizure‐free after using medication; the remaining patient did not take medication and continued to experience occasional auras. Wilcoxon rank sign comparison of NAA/Cr on initial 1H‐MRSI examination and follow‐up 1H‐MRSIs showed no significant difference (Z= 135, p = 0.893, 2‐tailed) for five seizure‐free patients. Conclusions: Neuronal dysfunction is present at an early stage of the epileptic process. NAA/Cr recovery in seizure‐free patients controlled with antiepileptic drugs is less evident, compared with successful surgical treatment. Thus, absence of seizures is not necessarily coupled with NAA/Cr improvement and observed variable response warrants further investigation.
The Ketogenic Diet Inhibits Epileptogenesis in EL Mice: A Genetic Model for Idiopathic Epilepsy
Authors: Todorova M. T. , Tandon P. , Madore R. A. , Stafstrom C. E. , Seyfried T. N. 
Published: August 2005

Summary:Purpose: The ketogenic diet (KD) is a high‐fat, low‐carbohydrate and ‐protein diet that has been used to treat refractory seizures in children for more than 75 years. However, little is known about how the KD inhibits seizures or its effects on epileptogenesis. Several animal models of epilepsy have responded favorably to KD treatment, but the KD has not been studied in animals with a genetic predisposition to seizures. Here we studied the antiepileptogenic effect of the KD in EL mice, an animal model for human idiopathic epilepsy.Methods: Young male EL mice (postnatal day 30) were randomly separated into two groups fed ad libitum with either the KD (treated, n = 21) or Agway chow (control, n = 19). The mice were weighed and tested for seizures once per week for a total of 10 weeks. The effects of the KD on plasma levels of ketone bodies and glucose were analyzed at several time points throughout the study. Associative learning was compared between treated and control animals using a water maze.Results: KD treatment delayed seizure onset in young male EL mice by 1 month; however, seizure protection was transient, inasmuch as the treated and control mice experienced a similar number and intensity of seizures after 6 weeks on the diet. Plasma glucose levels and associative learning were similar in the treated and control groups, but the plasma β‐hydroxybutyrate levels were significantly higher in mice on the KD. The level of ketosis, however, was not predictive of seizure protection in EL mice.Conclusion: The KD delayed seizure onset in EL mice, suggesting a transient protection against epileptogenesis. The KD did not influence plasma glucose levels or associative learning. Therefore, the EL mouse may serve as a good model to study the antiepileptogenic mechanisms of the KD.
The Clinical Usefulness of Ictal SPECT in Temporal Lobe Epilepsy: The Lateralization of Seizure Focus and Correlation with EEG
Authors: Lee Sang Kun , Lee Sung‐Hyn , Kim Seok‐Ki , Lee Dong‐Soo , Kim Ho 
Published: August 2005

Summary: Purpose: To analyze the relationship between ictal electroencephalography (EEG) and ictal single‐photon emission computed tomography (SPECT) and to evaluate the diagnostic usefulness of ictal SPECT as an independent presurgical evaluation technique. Methods: Sixty‐eight patients with temporal lobe epilepsy who underwent temporal lobectomy with good surgical outcome were included in this study. Ictal SPECT was performed during video‐EEG monitoring. The ictal EEG was analyzed in 5‐second intervals from the initiation of the ictal rhythm. Lateralized EEG dominance was determined by the amplitude, frequency, or regional patterns of ictal rhythm for each 5‐second interval. The total ictal EEG was divided into three periods: preinjection (maximum, 30 seconds), the initial part of the postinjection period (30 seconds), and the latter part of the postinjection period (30 to 60 seconds). The results of ictal SPECT were compared with the lateralized EEG dominance of each period and at seizure onset. Results: Fifty‐four of 68 ictal EEGs correctly lateralized seizure focus ipsilateral to the side of surgery. Ictal SPECT correctly laterlized the epileptogenic temporal lobe in 61 of 68 patients (mean injection time, 29.8 seconds from onset). Multivariate analysis indicated that only the EEG dominance of the prejection period correlated significantly with the concordant hyperperfusion of ictal SPECT. Correct lateralization of ictal SPECT occurred in 10 of 14 patients with nonlateralized ictal EEG. Conclusions: Preinjection neuronal activity seems to be important for the accurate interpretation of the hyperperfused patterns of ictal SPECT. Ictal SPECT is an independent and confirmatory presurgical evaluation technique.
Seizure Recurrence After a First Unprovoked Seizure in Childhood: A Prospective Study
Authors: Lizana J. Ramos , García E. Cassinello , Marina L. L. Carrasco , López M. Vázquez , Martín González M. , Hoyos A. Muñoz 
Published: August 2005

Summary: Purpose: To study the risk of recurrence after a first unprovoked seizure in childhood. Methods: All consecutive patients aged less than 14 years with one or more unprovoked seizures who were attended between January 1, 1987, and June 1, 1996, were included in a prospective study. Clinical features of patients attended after a first seizure and those attended after two or more seizures were compared. Recurrence risk in both groups was estimated by Kaplan‐Meier curves. Univariate and multivariate analyses of the potential predictors of recurrence risk were performed for the group of patients attended after a first seizure using the Cox proportional hazards model. Results: Included in the study were 217 children. Kaplan‐Meier estimate of recurrence risk was 64% at 5 years, when only patients being attended after a first epileptic seizure were included, compared with 74% when all patients were included. Significant differences in several clinical features were found between patients attended after a first seizure and those attended after two or more seizures. Univariate and multivariate analyses showed that in the overall cohort of patients attended after a first seizure, a symptomatic etiology increased the risk of recurrence, whereas a patient age of 3 to 10 years decreased this risk. In particular, the recurrence risk was 96% at 2 years for symptomatic seizures, compared with 46% for idiopathic/cryptogenic seizures. In the group of patients with idiopathic/cryptogenic seizures, an abnormal electroencephalogram and the occurrence of seizures during sleep increased the recurrence risk, whereas a patient aged 3 to 10 years reduced it. In the group of patients with symptomatic etiology, univariate analysis revealed that there was a lower recurrence risk for patients aged 3 to 10 years. This last finding was not maintained, however, in multivariate analysis. Conclusions: The recurrence risk depends on the inclusion criteria for enrolling patients. Several factors enable us to predict the recurrence risk after a first unprovoked seizure; the most important of these factors is the etiology of the seizures.
Enhancement of Progenitor Cell Division in the Dentate Gyrus Triggered by Initial Limbic Seizures in Rat Models of Epilepsy
Authors: Nakagawa Eiji , Aimi Yoshinari , Yasuhara Osamu , Tooyama Ikuo , Shimada Morimi , McGeer Patrick L. , Kimura Hiroshi 
Published: August 2005

Summary: Purpose: Mitogenic effects of seizures on granule cell progenitors in the dentate gyrus were studied in two rat models of epilepsy. We investigated which stage of epileptogenesis is critical for eliciting progenitor cell division and whether seizure‐induced neuronal degeneration is responsible for the enhancement of progenitor cell division. Methods: Seizures were induced by either kainic acid (KA) administration or electrical kindling. Neurogenesis of dentate granule cells was evaluated using the bromodeoxyuridine (BrdU) labeling method, and neuronal degeneration was assessed by in situ DNA fragmentation analysis. Results: After injection of KA, the number of BrdU‐positive granule cells began to increase at day 3 after the treatment, peaked at day 5, and returned to baseline at day 10. By day 13, the values were lower than control. After kindling, the number of BrdU‐positive cells began to increase after five consecutive experiences of stage I seizures. The increase occurred from day 1 to day 3 after the last electrical stimulation, but returned to baseline by day 7. After generalized seizures were well established, repeated stimulation did not facilitate division of granule cell progenitors. DNA fragmentation was noted in pyramidal neurons in the CA1, CA3, and hilus regions at 18 h after KA injection, but not in the kindling model. Conclusions: These observations indicate that a mechanism in epileptogenesis boosts dentate progenitor cell division, but progenitor cells may become unreactive to prolonged generalized seizures. Pyramidal neuronal degeneration is not necessary for triggering the upregulation. It is suggested that newly born granule cells may play a role in the network reorganization that occurs during epileptogenesis.
Characterization of Benzodiazepine Receptor Binding in Immature Rat Brain After Kainic Acid Administration
Authors: Rocha Luisa , González‐Trujano M. Eva , Jiménez Graciela , Gaona Andrés , Ondarza Rodolfo 
Published: August 2005

Summary: Purpose: To evaluate the effects of status epilepticus on benzodiazepine (BDZ) receptor binding in immature rat brain. Methods: Twenty‐four immature (15 days old) and six adult (90 days old) rats were used in this study. Status epilepticus was induced in immature animals by administration of kainic acid (7 mg/kg intraperitoneal), whereas adults rats received saline. Animals were killed 72 hours or 35 days after treatment, and their brains were used for in vitro autoradiography experiments to determine BDZ binding. Results: In basal conditions and compared with the adult group, immature animals presented reduced BDZ binding in the entorhinal cortex, substantia nigra pars reticulata, and periaqueductal gray. Seventy‐two hours after kainic acid–induced status epilepticus, immature rats showed significantly increased BDZ in the frontal (48%), cingulate (39%), sensorimotor (39%), piriform (57%), and entorhinal (59%) cortices, the medial (84%) and basolateral (27%) amygdaloid nuclei, the dentate gyrus (51%), and the substantia nigra pars reticulata (43%). Thirty‐five days after status epilepticus, immature rats displayed decreased BDZ binding in the entorhinal cortex (48%), dentate gyrus (36%), and fields CA1, CA2, and CA3 of Ammon's horn (30%). Conclusions: The present study demonstrates that status epilepticus and temporal lobe epilepsy produce a characteristic pattern of BDZ binding changes in the immature rat brain that differs from the one previously seen in adults.