The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Dolores E Lopez - One of the best experts on this subject based on the ideXlab platform.
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molecular and neurochemical substrates of the Audiogenic Seizure strains the gash sal model
Epilepsy & Behavior, 2017Co-Authors: Ana I Prietomartin, Dolores E Lopez, Luis Munoz, Daniel J Arocaaguilar, Francisco Sanchezsanchez, Julio Escribano, Carlos De CaboAbstract:article Purpose:AnimalmodelsofAudiogenicepilepsyareusefultoolstounderstandthemechanismsunderlyinghuman reflex epilepsies. There is accumulating evidence regarding behavioral, anatomical, electrophysiological, and genetic substrates of Audiogenic Seizure strains, but there are still aspects concerning their neurochemical basis that remain to be elucidated. Previous studies have shown the involved of γ-amino butyric acid (GABA) in Audiogenic Seizures. The aim of our research was to clarify the role of the GABAergic system in the generation of epileptic Seizures in the genetic Audiogenic Seizure-prone hamster (GASH:Sal) strain. Material and methods: We studied the K + /Cl � cotransporter KCC2 and β2-GABAA-type receptor (GABAAR) and β3-GABAAR subunit expressions in the GASH:Sal both at rest and after repeated sound-induced Seizures in dif- ferent brain regions using the Western blot technique. We also sequenced the coding region for the KCC2 gene both in wild- type and GASH:Sal hamsters. Results: Lower expressionof KCC2protein wasfoundinGASH:Salwhencomparedwith controls atrest inseveral brain areas: hippocampus, cortex, cerebellum, hypothalamus, pons-medulla, and mesencephalon. Repeated in- duction of Seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla. When compared to controls, the basal β2-GABAAR subunit in the GASH:Sal was overexpressed in the inferior colliculus, rest of the mesencephalon, and cerebellum, whereas basal β3 subunit levels were lower in the inferior colliculus and rest of the mesencephalon. Repeated Seizures increased β2 both in the inferior colliculus and in the hypothalamus and β3 in the hypothalamus. No differences in the KCC2 gene-coding region were found between GASH:Sal and wild-type hamsters. Conclusions: These data indicate that GABAergic system functioning is impaired in the GASH:Sal strain, and repeated Seizures seem to aggravate this dysfunction. These results have potential clinical relevance and support the validity of employing the GASH:Sal strain as a model to study the neurochemistry of genetic reflex epilepsy.
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pharmacological and neuroethological study of the acute and chronic effects of lamotrigine in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2017Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract The present study aimed to investigate the behavioral and anticonvulsant effects of lamotrigine (LTG) on the genetic Audiogenic Seizure hamster (GASH:Sal), an animal model of Audiogenic Seizure that is in the validation process. To evaluate the efficiency of acute and chronic treatments with LTG, GASH:Sals were treated with LTG either acutely via intraperitoneal injection (5–20 mg/kg) or chronically via oral administration (20–25 mg/kg/day). Their behavior was assessed via neuroethological analysis, and the anticonvulsant effect of LTG was evaluated based on the appearance and the severity of Seizures. The results showed that acute administration of LTG exerts an anticonvulsant effect at the lowest dose tested (5 mg/kg) and that chronic oral LTG treatment exerts an anticonvulsant effect at a dose of 20–25 mg/kg/day. Furthermore, LTG treatment induced a low rate of secondary adverse effects. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
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morphofunctional alterations in the olivocochlear efferent system of the genetic Audiogenic Seizure prone hamster gash sal
Epilepsy & Behavior, 2017Co-Authors: David Sanchezbenito, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Norberto Garciacairasco, Ricardo Gomeznieto, Sonia Hernandeznoriega, Adriana De Andrade Batista Murashima, Miguel Angelo HyppolitoAbstract:Abstract The genetic Audiogenic Seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic–clonic Seizures induced by external acoustic stimulation. The morphofunctional alterations in the auditory system of the GASH:Sal that may contribute to Seizure susceptibility have not been thoroughly determined. In this study, we analyzed the olivocochlear efferent system of the GASH:Sal from the organ of Corti, including outer and inner hair cells, to the olivocochlear neurons, including shell, lateral, and medial olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To achieve this, we carried out a multi-technical approach that combined auditory hearing screenings, scanning electron microscopy, morphometric analysis of labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results showed that the GASH:Sal exhibited higher auditory brain response (ABR) thresholds than their controls, as well as absence of distortion-product of otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE results also showed differences between the left and right ears, indicating asymmetrical hearing alterations in the GASH:Sal. These alterations in the peripheral auditory activity correlated with morphological alterations. At the cochlear level, the scanning electron microscopy analysis showed marked distortions of the stereocilia from basal to apical cochlear turns in the GASH:Sal, which were not observed in the control hamsters. At the brainstem level, MOC, LOC, and shell neurons had reduced soma areas compared with control animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated that the morphofunctional alterations of the olivocochlear efferent system are innate components of the GASH:Sal, which might contribute to their susceptibility to Audiogenic Seizures. This article is part of a Special Issue entitled “Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic”.
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pharmacological and neuroethological studies of three antiepileptic drugs in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2013Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract Epilepsy modeling is essential for understanding the basic mechanisms of the epileptic process. The Genetic Audiogenic Seizure Hamster (GASH:Sal) exhibits generalized tonic–clonic Seizures of genetic origin in response to sound stimulation and is currently being validated as a reliable model of epilepsy. Here, we performed a pharmacological and neuroethological study using well-known and widely used antiepileptic drugs (AEDs), including phenobarbital (PB), valproic acid (VPA), and levetiracetam (LEV). The intraperitoneal administration of PB (5–20 mg/kg) and VPA (100–300 mg/kg) produced a dose-dependent decrease in GASH:Sal Audiogenic Seizure severity scores. The administration of LEV (30–100 mg/kg) did not produce a clear effect. Phenobarbital showed a short plasmatic life and had a high antiepileptic effect starting at 10 mg/kg that was accompanied by ataxia. Valproic acid acted only at high concentrations and was the AED with the most ataxic effects. Levetiracetam at all doses also produced sedation and ataxia side effects. We conclude that the GASH:Sal is a reliable genetic model of epilepsy suitable to evaluate AEDs.
Consuelo Sancho - One of the best experts on this subject based on the ideXlab platform.
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pharmacological and neuroethological study of the acute and chronic effects of lamotrigine in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2017Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract The present study aimed to investigate the behavioral and anticonvulsant effects of lamotrigine (LTG) on the genetic Audiogenic Seizure hamster (GASH:Sal), an animal model of Audiogenic Seizure that is in the validation process. To evaluate the efficiency of acute and chronic treatments with LTG, GASH:Sals were treated with LTG either acutely via intraperitoneal injection (5–20 mg/kg) or chronically via oral administration (20–25 mg/kg/day). Their behavior was assessed via neuroethological analysis, and the anticonvulsant effect of LTG was evaluated based on the appearance and the severity of Seizures. The results showed that acute administration of LTG exerts an anticonvulsant effect at the lowest dose tested (5 mg/kg) and that chronic oral LTG treatment exerts an anticonvulsant effect at a dose of 20–25 mg/kg/day. Furthermore, LTG treatment induced a low rate of secondary adverse effects. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
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pharmacological and neuroethological studies of three antiepileptic drugs in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2013Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract Epilepsy modeling is essential for understanding the basic mechanisms of the epileptic process. The Genetic Audiogenic Seizure Hamster (GASH:Sal) exhibits generalized tonic–clonic Seizures of genetic origin in response to sound stimulation and is currently being validated as a reliable model of epilepsy. Here, we performed a pharmacological and neuroethological study using well-known and widely used antiepileptic drugs (AEDs), including phenobarbital (PB), valproic acid (VPA), and levetiracetam (LEV). The intraperitoneal administration of PB (5–20 mg/kg) and VPA (100–300 mg/kg) produced a dose-dependent decrease in GASH:Sal Audiogenic Seizure severity scores. The administration of LEV (30–100 mg/kg) did not produce a clear effect. Phenobarbital showed a short plasmatic life and had a high antiepileptic effect starting at 10 mg/kg that was accompanied by ataxia. Valproic acid acted only at high concentrations and was the AED with the most ataxic effects. Levetiracetam at all doses also produced sedation and ataxia side effects. We conclude that the GASH:Sal is a reliable genetic model of epilepsy suitable to evaluate AEDs.
James R Coleman - One of the best experts on this subject based on the ideXlab platform.
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Audiogenic Seizure activity following hsv 1 gad65 sense or antisense injection into inferior colliculus of long evans rat
Epilepsy & Behavior, 2017Co-Authors: James R Coleman, Karen C Thompson, Marlene A Wilson, Steven P WilsonAbstract:Abstract Herpes virus technology involving manipulation of GAD65 was used to study effects on Audiogenic Seizures (AGS). Audiogenic Seizure behaviors were examined following injections of replication-defective herpes simplex virus (HSV-1) vectors incorporating sense or antisense toward GAD65 along with 10% lac -Z into the central nucleus of inferior colliculus (CNIC) of Long–Evans rats. In Seizure-sensitive animals developmentally primed by intense sound exposure, injection of GAD65 in the sense orientation increased wild running latencies and reduced incidence of clonus compared with lac -Z only, unoperated, and vehicle Seizure groups. In contrast, infection of CNIC with GAD65 antisense virus resulted in 100% incidence of wild running and clonus behaviors in AGS animals. Unprimed animals not operated continued to show uniform absence of Seizure activity. Administration of GAD65 antisense virus into CNIC produced novel wild running and clonus behaviors in some unprimed animals. Staining for β-galactosidase in all vector animals revealed no differences in pattern or numbers of immunoreactive cells at injection sites. Qualitatively, typical small and medium multipolar/stellate and medium fusiform neurons appeared in the CNIC of vector animals. These results demonstrate that HSV-1 vector constructs implanted into the CNIC can predictably influence incidence and severity of AGS and suggest that viral vectors can be useful in studying GABA mechanisms with potential for therapeutic application in epilepsy. This article is part of a Special Issue entitled “Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic”.
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latency alterations of the auditory brainstem response in Audiogenic Seizure prone long evans rats
Epilepsy Research, 1999Co-Authors: James R Coleman, Karen C Ross, Megan M Mullaney, William A CooperAbstract:Abstract Audiogenic Seizure susceptibility in the normally Seizure-resistant Long-Evans rat may result from altered processing in the auditory pathway. Representative waveform latencies of the auditory brainstem responses (ABR) were recorded to examine generator alterations at different levels of the auditory neuraxis. Male Long-Evans rats primed for Audiogenic Seizures (AGS) on PND 14 with a 10 kHz pure tone at 120 dB SPL for 8 min were tested for AGS on PND 28 with 120 dB SPL continuous white noise. Primed subjects displayed wild running culminating in clonic convulsions. Following behavioral testing at 4–6 months, vertex recordings of ABR waves Ia–VI were made in anesthetized subjects using pure tone stimulus bursts. AGS subjects showed marginally elevated ABR thresholds. Shorter ABR wave latencies were elicited in AGS subjects for peripheral and central auditory components with stimulus intensities above 50 dB PeSPL at 8 and 40 kHz. Interpeak intervals were reduced for waves Ia–V and III–V in AGS subjects. These results reveal that intense sound stimulation during a sensitive period of development later reduces processing time at higher intensity levels.
Luis Munoz - One of the best experts on this subject based on the ideXlab platform.
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molecular and neurochemical substrates of the Audiogenic Seizure strains the gash sal model
Epilepsy & Behavior, 2017Co-Authors: Ana I Prietomartin, Dolores E Lopez, Luis Munoz, Daniel J Arocaaguilar, Francisco Sanchezsanchez, Julio Escribano, Carlos De CaboAbstract:article Purpose:AnimalmodelsofAudiogenicepilepsyareusefultoolstounderstandthemechanismsunderlyinghuman reflex epilepsies. There is accumulating evidence regarding behavioral, anatomical, electrophysiological, and genetic substrates of Audiogenic Seizure strains, but there are still aspects concerning their neurochemical basis that remain to be elucidated. Previous studies have shown the involved of γ-amino butyric acid (GABA) in Audiogenic Seizures. The aim of our research was to clarify the role of the GABAergic system in the generation of epileptic Seizures in the genetic Audiogenic Seizure-prone hamster (GASH:Sal) strain. Material and methods: We studied the K + /Cl � cotransporter KCC2 and β2-GABAA-type receptor (GABAAR) and β3-GABAAR subunit expressions in the GASH:Sal both at rest and after repeated sound-induced Seizures in dif- ferent brain regions using the Western blot technique. We also sequenced the coding region for the KCC2 gene both in wild- type and GASH:Sal hamsters. Results: Lower expressionof KCC2protein wasfoundinGASH:Salwhencomparedwith controls atrest inseveral brain areas: hippocampus, cortex, cerebellum, hypothalamus, pons-medulla, and mesencephalon. Repeated in- duction of Seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla. When compared to controls, the basal β2-GABAAR subunit in the GASH:Sal was overexpressed in the inferior colliculus, rest of the mesencephalon, and cerebellum, whereas basal β3 subunit levels were lower in the inferior colliculus and rest of the mesencephalon. Repeated Seizures increased β2 both in the inferior colliculus and in the hypothalamus and β3 in the hypothalamus. No differences in the KCC2 gene-coding region were found between GASH:Sal and wild-type hamsters. Conclusions: These data indicate that GABAergic system functioning is impaired in the GASH:Sal strain, and repeated Seizures seem to aggravate this dysfunction. These results have potential clinical relevance and support the validity of employing the GASH:Sal strain as a model to study the neurochemistry of genetic reflex epilepsy.
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pharmacological and neuroethological study of the acute and chronic effects of lamotrigine in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2017Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract The present study aimed to investigate the behavioral and anticonvulsant effects of lamotrigine (LTG) on the genetic Audiogenic Seizure hamster (GASH:Sal), an animal model of Audiogenic Seizure that is in the validation process. To evaluate the efficiency of acute and chronic treatments with LTG, GASH:Sals were treated with LTG either acutely via intraperitoneal injection (5–20 mg/kg) or chronically via oral administration (20–25 mg/kg/day). Their behavior was assessed via neuroethological analysis, and the anticonvulsant effect of LTG was evaluated based on the appearance and the severity of Seizures. The results showed that acute administration of LTG exerts an anticonvulsant effect at the lowest dose tested (5 mg/kg) and that chronic oral LTG treatment exerts an anticonvulsant effect at a dose of 20–25 mg/kg/day. Furthermore, LTG treatment induced a low rate of secondary adverse effects. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
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pharmacological and neuroethological studies of three antiepileptic drugs in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2013Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract Epilepsy modeling is essential for understanding the basic mechanisms of the epileptic process. The Genetic Audiogenic Seizure Hamster (GASH:Sal) exhibits generalized tonic–clonic Seizures of genetic origin in response to sound stimulation and is currently being validated as a reliable model of epilepsy. Here, we performed a pharmacological and neuroethological study using well-known and widely used antiepileptic drugs (AEDs), including phenobarbital (PB), valproic acid (VPA), and levetiracetam (LEV). The intraperitoneal administration of PB (5–20 mg/kg) and VPA (100–300 mg/kg) produced a dose-dependent decrease in GASH:Sal Audiogenic Seizure severity scores. The administration of LEV (30–100 mg/kg) did not produce a clear effect. Phenobarbital showed a short plasmatic life and had a high antiepileptic effect starting at 10 mg/kg that was accompanied by ataxia. Valproic acid acted only at high concentrations and was the AED with the most ataxic effects. Levetiracetam at all doses also produced sedation and ataxia side effects. We conclude that the GASH:Sal is a reliable genetic model of epilepsy suitable to evaluate AEDs.
Jose Antonio Cortes De Oliveira - One of the best experts on this subject based on the ideXlab platform.
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morphofunctional alterations in the olivocochlear efferent system of the genetic Audiogenic Seizure prone hamster gash sal
Epilepsy & Behavior, 2017Co-Authors: David Sanchezbenito, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Norberto Garciacairasco, Ricardo Gomeznieto, Sonia Hernandeznoriega, Adriana De Andrade Batista Murashima, Miguel Angelo HyppolitoAbstract:Abstract The genetic Audiogenic Seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic–clonic Seizures induced by external acoustic stimulation. The morphofunctional alterations in the auditory system of the GASH:Sal that may contribute to Seizure susceptibility have not been thoroughly determined. In this study, we analyzed the olivocochlear efferent system of the GASH:Sal from the organ of Corti, including outer and inner hair cells, to the olivocochlear neurons, including shell, lateral, and medial olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To achieve this, we carried out a multi-technical approach that combined auditory hearing screenings, scanning electron microscopy, morphometric analysis of labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results showed that the GASH:Sal exhibited higher auditory brain response (ABR) thresholds than their controls, as well as absence of distortion-product of otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE results also showed differences between the left and right ears, indicating asymmetrical hearing alterations in the GASH:Sal. These alterations in the peripheral auditory activity correlated with morphological alterations. At the cochlear level, the scanning electron microscopy analysis showed marked distortions of the stereocilia from basal to apical cochlear turns in the GASH:Sal, which were not observed in the control hamsters. At the brainstem level, MOC, LOC, and shell neurons had reduced soma areas compared with control animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated that the morphofunctional alterations of the olivocochlear efferent system are innate components of the GASH:Sal, which might contribute to their susceptibility to Audiogenic Seizures. This article is part of a Special Issue entitled “Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic”.
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pharmacological and neuroethological study of the acute and chronic effects of lamotrigine in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2017Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract The present study aimed to investigate the behavioral and anticonvulsant effects of lamotrigine (LTG) on the genetic Audiogenic Seizure hamster (GASH:Sal), an animal model of Audiogenic Seizure that is in the validation process. To evaluate the efficiency of acute and chronic treatments with LTG, GASH:Sals were treated with LTG either acutely via intraperitoneal injection (5–20 mg/kg) or chronically via oral administration (20–25 mg/kg/day). Their behavior was assessed via neuroethological analysis, and the anticonvulsant effect of LTG was evaluated based on the appearance and the severity of Seizures. The results showed that acute administration of LTG exerts an anticonvulsant effect at the lowest dose tested (5 mg/kg) and that chronic oral LTG treatment exerts an anticonvulsant effect at a dose of 20–25 mg/kg/day. Furthermore, LTG treatment induced a low rate of secondary adverse effects. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
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pharmacological and neuroethological studies of three antiepileptic drugs in the genetic Audiogenic Seizure hamster gash sal
Epilepsy & Behavior, 2013Co-Authors: B Barrerabailon, Jose Antonio Cortes De Oliveira, Dolores E Lopez, Luis Munoz, Norberto Garciacairasco, Consuelo SanchoAbstract:Abstract Epilepsy modeling is essential for understanding the basic mechanisms of the epileptic process. The Genetic Audiogenic Seizure Hamster (GASH:Sal) exhibits generalized tonic–clonic Seizures of genetic origin in response to sound stimulation and is currently being validated as a reliable model of epilepsy. Here, we performed a pharmacological and neuroethological study using well-known and widely used antiepileptic drugs (AEDs), including phenobarbital (PB), valproic acid (VPA), and levetiracetam (LEV). The intraperitoneal administration of PB (5–20 mg/kg) and VPA (100–300 mg/kg) produced a dose-dependent decrease in GASH:Sal Audiogenic Seizure severity scores. The administration of LEV (30–100 mg/kg) did not produce a clear effect. Phenobarbital showed a short plasmatic life and had a high antiepileptic effect starting at 10 mg/kg that was accompanied by ataxia. Valproic acid acted only at high concentrations and was the AED with the most ataxic effects. Levetiracetam at all doses also produced sedation and ataxia side effects. We conclude that the GASH:Sal is a reliable genetic model of epilepsy suitable to evaluate AEDs.
