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Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [PET data evaluated at 2 h showed hyper-uptake of [This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.

Some reports have described that a high fructose diet is associated with a deficit of hippocampus-dependent cognitive functions. In this study, we have evaluated the effects of fructose on spatial memory and molecular markers in the hippocampus and prefrontal cortex and analyzed whether those alterations are reversible. Male Wistar rats (

Fructose ingestion elicits a diversity of brain alterations, but it is unknown how it affects N-methyl-D-Aspartate receptors (NMDAr). Here, we analyzed the expression of NMDAr subunits and protein kinases after the long-term dietary fructose intake. Since NMDAr are related to epileptogenesis, we also examined whether fructose increases the susceptibility to seizures after the microinjection of kainic acid (KA) in the rat hippocampus. Wistar rats were randomly divided into water (control) and fructose groups. For twelve weeks, groups had ad libitum access to water or fructose solution (10% w/v). After treatment, hippocampal protein expression of NMDAr subunits and protein kinases involved in NMDAr regulation were analyzed. Additionally, electroencephalographic and behavioral changes related to seizures were evaluated after the microinjection of a sub-convulsive dose of KA in the hippocampus. Fructose induced the decrease of NR1 and, conversely, the increase of NR2A subunits expression in the hippocampus. Also, the phosphorylation of protein kinase C alpha (PKCα) and c-Src increased significantly. No electroencephalographic or behavioral patterns related to convulsive motor seizures were observed in the control group. However, all the rats that ingested fructose showed stage 3 seizures (forelimb clonus) and a significant increase in the number of wet-dog shakes. Moreover, electroencephalographic recordings revealed pronounced epileptiform activity and increased total spectral power at 30 and 60 min after the microinjection of KA. This study shows for the first time that fructose intake exacerbates the seizures induced by KA. Therefore, we propose that this proconvulsant effect could be mediated by changes in NMDAr subunits expression and increased activation of kinases modulating NMDAr function.

Denisse Arcos-Montoya,1 Talia Wegman-Ostrosky,2,3 Sonia Mejía-Pérez,4 Marisol De la Fuente-Granada,1 Ignacio Camacho-Arroyo,5 Alejandro García-Carrancá,6 Marco A Velasco-Velázquez,7 Joaquín Manjarrez-Marmolejo,8 Aliesha González-Arenas1 1Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México; 2Dirección de Investigación, Instituto Nacional Cancerología, Ciudad de México, México; 3División de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, México; 4Subdirección de Neurocirugía, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México; 5Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México; 6Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México e Instituto Nacional de Cancerología, Ciudad de México, México; 7Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México; 8Laboratorio de Fisiología de la Formación Reticular, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, MéxicoCorrespondence: Aliesha González-ArenasDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, 04510, MéxicoTel +52 5556 22 9209Email alieshag@iibiomedicas.unam.mxIntroduction: Astrocytomas are the most common and aggressive primary brain tumors, and they are classified according to the degree of malignancy on a scale of I to IV, in which grade I is the least malignant and grade IV the highest. Many factors are related to astrocytomas progression as progesterone receptor (PR), whose transcriptional activity could be regulated by phosphorylation by protein kinase C alpha (PKCα) at the residue Ser400. Our aim was to investigate if PR phosphorylation together with PKCα expression could be used as a prognostic factor for astrocytomas malignancy.Methods: By immunofluorescence, we detected the content of PKCα, PR and its phosphorylation at Ser400 in 46 biopsies from Mexican patients with different astrocytoma malignancy grades; by bioinformatic tools using TCGA data, we evaluated the expression of PR and PKCα mRNA according to astrocytoma malignancy grades. For all statistical analyses, significance was p< 0.05.Results: We detected a positive correlation between the tumor grade and the content of PKCα, PR and its phosphorylation at Ser400, as well as the intracellular colocalization of these proteins. Interestingly, using an in silico assay, we found that the PR and PKCα expression at mRNA level has an inverse ratio with astrocytomas tumor grade.Discussion: These results indicate that PR and its phosphorylation at Ser400 site, as well as PKCα and their colocalization, could be considered as possible malignancy biomarkers for astrocytomas grades I–IV.Keywords: astrocytoma, glioblastoma, progesterone receptor, protein kinase C alpha, biomarker

Brain metabolic processes are not fully characterized in the kainic acid (KA)-induced Status Epilepticus (KASE). Thus, we evaluated the usefulness ofSixteen male Wistar rats underwent FDG-PET scans at basal state and after KA injection. FDG-PET images were normalized to an MRI-based atlas and segmented to locate regions. Standardized uptake values (SUV) were obtained at several time points. EEGs and cell viability by histological analysis, were also evaluated.FDG-PET data showed changes in regions such as: amygdala, hippocampus, accumbens, entorhinal cortex, motor cortex and hypothalamus. Remarkably, hippocampal hypermetabolism was found (mean SUV = 2.66 ± 0.057) 2 h after KA administration, while hypometabolism at 24 h (mean SUV = 1.83 ± 0.056) vs basal values (mean SUV = 2.19 ± 0.057). EEG showed increased spectral power values 2 h post-KA administration. Hippocampal viable-cell counting 24 h after KA was decreased, while Fluoro-Jade B-positive cells were increased, as compared to control rats, coinciding with the hypometabolism detected in the same region by semi-quantitative FDG-PET at 24 h after KASE.PET is suitable to measure metabolic brain changes in the rat model of status epilepticus induced by KA (KASE) at the first 24 h, compared to that of EEG; PET data may also be sensitive to cell viability.

Objective Brain metabolic processes are not fully characterized in the kainic acid (KA)-induced Status Epilepticus (KASE). Thus, we evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an experimental strategy to evaluate in vivo, in a non-invasive way, the glucose consumption in several brain regions, in a semi-quantitative study to compare and to correlate with data from electroencephalography and histology studies. Methods. Sixteen male Wistar rats underwent FDG-PET scans at basal state and after KA injection. FDG-PET images were normalized to an MRI-based atlas and segmented to locate regions. Standardized uptake values (SUV) were obtained at several time points. EEGs and cell viability by histological analysis, were also evaluated. Results FDG-PET data showed changes in regions such as: amygdala, hippocampus, accumbens, entorhinal cortex, motor cortex and hypothalamus. Remarkably, hippocampal hypermetabolism was found (mean SUV = 2.66 ± 0.057) 2 h after KA administration, while hypometabolism at 24 h (mean SUV = 1.83 ± 0.056) vs basal values (mean SUV = 2.19 ± 0.057). EEG showed increased spectral power values 2 h post-KA administration. Hippocampal viable-cell counting 24 h after KA was decreased, while Fluoro-Jade B-positive cells were increased, as compared to control rats, coinciding with the hypometabolism detected in the same region by semi-quantitative FDG-PET at 24 h after KASE. Conclusions PET is suitable to measure metabolic brain changes in the rat model of status epilepticus induced by KA (KASE) at the first 24 h, compared to that of EEG; PET data may also be sensitive to cell viability.

Background Gap junctions are clusters of intercellular channels allowing the bidirectional pass of ions directly into the cytoplasm of adjacent cells. Electrical coupling mediated by gap junctions plays a role in the generation of highly synchronized electrical activity. The hypersynchronous neuronal activity is a distinctive characteristic of convulsive events. Therefore, it has been postulated that enhanced gap junctional communication is an underlying mechanism involved in the generation and maintenance of seizures. There are some chemical compounds characterized as gap junction blockers because of their ability to disrupt the gap junctional intercellular communication. Objective Hence, the aim of this review is to analyze the available data concerning the effects of gap junction blockers specifically in seizure models. Results Carbenoxolone, quinine, mefloquine, quinidine, anandamide, oleamide, heptanol, octanol, meclofenamic acid, niflumic acid, flufenamic acid, glycyrrhetinic acid and retinoic acid have all been evaluated on animal seizure models. In vitro, these compounds share anticonvulsant effects typically characterized by the reduction of both amplitude and frequency of the epileptiform activity induced in brain slices. In vivo, gap junction blockers modify the behavioral parameters related to seizures induced by 4-aminopyridine, pentylenetetrazole, pilocarpine, penicillin and maximal electroshock. Conclusion Although more studies are still required, these molecules could be a promising avenue in the search for new pharmaceutical alternatives for the treatment of epilepsy.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep&ndash, wake cycle, locomotion, and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep&ndash, wake cycle of rats, increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons, which may be responsible for alterations of the sleep&ndash, wake cycle.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

Status epilepticus (SE) is a serious medical condition, as it may trigger epileptogenesis. SE produces continuous generalized seizures resulting in irreversible brain damage. Therefore, the use of neuroprotective agents to prevent cell damage, may reduce the impact of SE. The use of diazepam (DZP), has shown limited neuroprotective effect in SE patients. According to previous reports, dapsone (DDS) is able to reduce both cell damage and seizures, when administered 30 min before the onset of seizures. This study is aimed to evaluate the ability of DDS, alone or in combination with DZP starting their administration once the SE is onset to evaluate the control of seizures in rats. Results showed a reduced convulsive electrical activity after 30 min, 1 and 2 h after SE induced by kainic acid (KA) administration, in the animals treated with DZP alone or in combination with DDS. At 24 h, we observed electrical activity similar to baseline in all groups receiving treatment. The animals treated with DDS and DZP alone or in combination showed an increase in the number of viable pyramidal cells but only the combination showed a lower number of damaged pyramidal neurons of hippocampal CA3. In conclusion, DDS plus DZP was able to control SE and to prevent SE-induced damage, when administered in combination with DZP. As DDS is already in use for patients with leprosy, that combination may be a safe, good option for human cases of SE.

Objective Quinine (QUIN) and carbenoxolone (CNX) elicit anticonvulsant effects typically characterized by the reduction of the epileptiform activity as well as changes in behavioral parameters related to seizures. Therefore, the aim of this study was to analyze the effects of these molecules on the anticonvulsant activity of some classical antiepileptic drugs. Methods Male Wistar rats were used. Valproate (VPA), phenytoin (PHT), or carbamazepine (CBZ) was administered at sub-therapeutic doses for intraperitoneal via. Subsequently, animals were administered with a single dose of QUIN or CNX. The anticonvulsant activity was evaluated with the maximal electroshock (MES) test and pentylenetetrazole (PTZ) administration. Additionally, the plasma levels of CBZ were determined using an HPLC method. Results All the control rats presented generalized tonic-clonic seizures after the MES test or the administration of PTZ. For the MES test, all of the antiepileptic drugs increased their anticonvulsant activity when were co-administered with QUIN. For the PTZ test, only the combination CBZ plus QUIN significantly increased the percentage of protection against the generalized tonic-clonic seizures. The co-administration of CBZ plus QUIN resulted in an augmented concentration of CBZ in plasma. Discussion The present study shows that QUIN and CNX enhance the anticonvulsant activity of some classical antiepileptic drugs. However, only the combination CBZ/QUIN had significant effects on both MES and PTZ models. Such anticonvulsant activity could be attributed to increased levels of CBZ in plasma. We propose that these molecules could improve the pharmacological actions of antiepileptic drugs administered at sub-therapeutic doses.

Background and Aims Progesterone (P) is a steroid hormone involved in the development of several types of cancer including astrocytomas, the most common and malignant brain tumors. We undertook this study to investigate the effects of P on the growth and infiltration of a tumor caused by the xenotransplant of U87 cells derived from a human astrocytoma grade IV (glioblastoma) in the cerebral cortex of male rats and the participation of intracellular progesterone receptor (PR) on these effects. Methods Eight weeks after the implantation of U87 cells in the cerebral cortex, we administered phosphorothioated antisense oligodeoxynucleotides (ODNs) to silence the expression of PR. This treatment lasted 15 days and was administered at the site of glioblastoma cells implantation using Alzet osmotic pumps. Vehicle (propylene glycol) or P 4 (400 μg/100 g) was subcutaneously injected for 14 days starting 1 day after the beginning of ODN administration. Results We observed that P significantly increased glioblastoma tumor area and infiltration length as compared with vehicle, whereas PR antisense ODNs blocked these effects. Conclusion P, through the interaction with PR, increases the area and infiltration of a brain tumor formed from the xenotransplant of human glioblastoma-derived U87 cells in the cerebral cortex of the rat.

Pontine reticular formation (PRF) is involved in the generation and maintenance of generalized epileptic seizures. Carbenoxolone (CBX) is a gap junction blocker with anticonvulsant properties. Therefore, the present study was designed to explore the effects of CBX microinjected into the pontis caudalis nucleus (PnC) on generalized tonic–clonic seizures (GTCS) and epileptiform activity induced by pentylenetetrazole (PTZ). All control rats presented GTCS after a single dose of PTZ. The microinjection of CBX into the PnC reduced the GTCS incidence induced by PTZ. Moreover, the CBX significantly increased the latency to the first myoclonic jerk. Additionally, CBX significantly decreased the spectral power and the amplitude of the epileptiform activity induced by PTZ. By contrast, the microinjection of a gap junction opener (trimethylamine) did not cause anticonvulsant effects and even increased the duration of the GTCS. These findings suggest that the PnC is a particular nucleus where the CBX could exert its action mechanisms and elicit anticonvulsant effects.

In this work we have determined the role of the 26S proteasome in the regulation of the content of progesterone receptors (PR-A and PR-B), estrogen receptors (ER-alpha and ER-beta), the coactivator SRC-1 and the corepressor SMRT in the rat brain during the estrous cycle. The 26S proteasome inhibitor MG132 was injected once into the lateral ventricle on proestrous day; and 24h later, on estrous day we evaluated the content of PR and ER isoforms, SRC-1 and SMRT in the hypothalamus, the preoptic area and the hippocampus by Western blot. A significant increase in the content of both PR isoforms, ER-beta and SRC-1 was observed after the administration of MG132 in the three studied cerebral regions. SMRT content was increased in the hypothalamus and the preoptic area and a significant increase in ER-alpha content was only observed in the preoptic area. These results suggest that essential proteins that participate in progesterone and estrogen actions in the brain should be regulated by the 26S proteasome in a tissue-specific manner in physiological conditions.

Background. In a previous study we reported that 4,4′diaminodiphenylsulfone (dapsone) has anticonvulsant activity using kainic acid (KA) model. This work shows the behavioral and electrophysiologic changes caused by systemic application of several dapsone derivatives. These derivatives include disodium salt of 4,4′-diaminodifenylsulfone N,N′-diformaldehyde sulfoxylate (I), 4,4′-diaminodiphenylsulfone N,N′-didextrose sulfonate (II), sodium dibisulfite 4,4′-biscinamilidenamindiphenyl sulfone (III), and N,N′-dimethyl-4,4′-dimethylphenylsulfone (IV), which were synthesized and purified in our laboratory. Methods. A KA model was used to provoke limbic seizures. Limbic seizures were provoked by injection, KA, and electrophysiologic recorder at the following concentrations: 6.25 and 12.50 mg/kg of III and 6.25 and 12.50 mg/kg of IV. Results. Compounds III and IV caused decrease of postdischarges; we found percentage of protection of 55.60 and 70.78%, respectively. This showed possible anticonvulsant activity of these compounds (III and IV), while I and II showed no significant changes. We also studied whether there was a dose-dependence relationship, and different doses of compound IV were evaluated (25.00, 12.50, 6.25, 3.12, and 1.62 mg/kg). We found that greatest anticonvulsant effect occurred using doses of 3.12 and 6.25 mg/kg (two of the three lowest doses). Conclusions. We concluded that IV at doses of 3.25 and 6.25 mg/kg has anticonvulsant effect because it diminished duration of the first limbic seizure induced by KA; latency of first limbic seizure crisis was also increased. Both facts demonstrated possible therapeutic application of compound IV as anticonvulsant.

Background Mefloquine can cross the blood–brain barrier and block the gap junction intercellular communication in the brain. Enhanced electrical coupling mediated by gap junctions is an underlying mechanism involved in the generation and maintenance of seizures. For this reason, the aim of this study was to analyze the effects of the systemic administration of mefloquine on tonic-clonic seizures induced by two acute models such as pentylenetetrazole and maximal electroshock. Results All the control rats presented generalized tonic-clonic seizures after the administration of pentylenetetrazole. However, the incidence of seizures induced by pentylenetetrazole significantly decreased in the groups administered systematically with 40 and 80 mg/kg of mefloquine. In the control group, none of the rats survived after the generalized tonic-clonic seizures induced by pentylenetetrazole, but survival was improved by mefloquine. Besides, mefloquine significantly modified the total spectral power as well as the duration, amplitude and frequency of the epileptiform activity induced by pentylenetetrazole. For the maximal electroshock model, mefloquine did not change the occurrence of tonic hindlimb extension. However, this gap junction blocker significantly decreased the duration of the tonic hindlimb extension induced by the acute electroshock. Conclusions These data suggest that mefloquine at low doses might be eliciting some anticonvulsant effects when is systemically administered to rats.

Preclinical investigation of brain tumors is frequently carried out by means of intracranial implantation of brain tumor xenografts or allografts, with subsequent analysis of tumor growth using conventional histopathology. However, very little has been reported on the use contrast-enhanced techniques in micro-CT imaging for the study of malignant brain tumors in small animal models. The aim of this study has been to test a protocol for ex vivo imaging of murine brain models of glioblastoma multiforme (GBM) after treatment with non-ionic iodinated solution, using an in-house developed laboratory micro-CT. We have found that the best compromise between acquisition time and image quality is obtained using a 50 kVp, 0.5 mAs, 1° angular step on a 360 degree orbit acquisition protocol, with 70 μm reconstructed voxel size using the Feldkamp algorithm. With this parameters up to 4 murine brains can be scanned in tandem in less than 15 minutes. Image segmentation and analysis of three sample brains allowed identif...

Progesterone (P4) promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160 μL), P4(1 mg), RU486 (5 mg), or P4+ RU486 (1 mg and 5 mg, resp.) for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4effects. All rats treated with P4showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4+ RU486, respectively, presented it. Our data suggest that P4promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor.

"México cuenta con una ancestral tradición en el uso de tratamientos naturales, como parte del repunte de la medicina tradicional herbolaria; se revisaron las características etnobotánicas de la Lavandula officinalis (Lavanda) y se diseñó una metodología para obtener e identificar varios de los diferentes agentes bioactivos y valorar su posible efecto sedante."

In a previous study we reported that 4,4'diaminodiphenylsulfone (dapsone) has anticonvulsant activity using kainic acid (KA) model. This work shows the behavioral and electrophysiologic changes caused by systemic application of several dapsone derivatives. These derivatives include disodium salt of 4,4'-diaminodifenylsulfone N,N'-diformaldehyde sulfoxylate (I), 4,4'-diaminodiphenylsulfone N,N'-didextrose sulfonate (II), sodium dibisulfite 4,4'-biscinamilidenamindiphenyl sulfone (III), and N,N'-dimethyl-4,4'-dimethylphenylsulfone (IV), which were synthesized and purified in our laboratory.A KA model was used to provoke limbic seizures. Limbic seizures were provoked by injection, KA, and electrophysiologic recorder at the following concentrations: 6.25 and 12.50 mg/kg of III and 6.25 and 12.50 mg/kg of IV.Compounds III and IV caused decrease of postdischarges; we found percentage of protection of 55.60 and 70.78%, respectively. This showed possible anticonvulsant activity of these compounds (III and IV), while I and II showed no significant changes. We also studied whether there was a dose-dependence relationship, and different doses of compound IV were evaluated (25.00, 12.50, 6.25, 3.12, and 1.62 mg/kg). We found that greatest anticonvulsant effect occurred using doses of 3.12 and 6.25 mg/kg (two of the three lowest doses).We concluded that IV at doses of 3.25 and 6.25 mg/kg has anticonvulsant effect because it diminished duration of the first limbic seizure induced by KA; latency of first limbic seizure crisis was also increased. Both facts demonstrated possible therapeutic application of compound IV as anticonvulsant.

We tested the ability of dapsone (4,4'-diamino-diphenyl sulfone) to attenuate kainic acid-induced seizures. We observed that 9.375 and 12.5 mg/kg doses of dapsone administered 30 min before a single kainic acid (10 mg/kg) i.p. injection were able to decrease the time of electroencephalographic seizures by 52% and 82%, respectively, as compared with rats administered with 10 mg/kg kainic acid only. The 12.5 mg/kg dose of dapsone was also able to diminish both kainic acid-evoked body and head shakes (58%) and kainic acid-induced mortality (75%). These results suggest that dapsone could be used in clinical trials as anticonvulsant.