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Effect of Unilateral Low-Frequency Stimulation of Hippocampus on Rapid Kindling—Induced Seizure Development in Rats

Neuroscience & Medicine 2012年第2期3卷 174-180页

作者： Lucas Toibaro Magdalena Pereyra Julieta Pastorino Ariela Smigliani Florencia Ocariz Germán Ortmann maría milagros galardi maría Belén Gori Silvia Kochen Epilepsy Laboratory Institute of Cellular Biology and Neuroscience—National Council for Scientific and Technical Research (CONICET) School of Medicine University of Buenos Aires Buenos Aires Argentina

Since the last decade deep brain stimulation has been proposed as an alternative treatment for patients who do not become seizure-free with the current pharmacological treatments and cannot undergo resective surgical procedure. However, the optimal stimulation parameters remain undetermined and active research in humans and animals is necessary. The present study was designed to investigate the effect of unilateral Low Frequency Stimulation (LFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK;n = 6) received only RK stimulus, while the treated group (LFS-hRK;n = 8) received also LFS (biphasic square wave pulses, 1 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing on day 3, 62% (P < 0.05) of the animals receiving LFS treatment were still not fully kindled staying in stages 0-III (P < 0.01). The number of stimulations needed to achieve generalized seizures (stage IV-V of Racine scale) was significantly higher (P < 0.05) in the LFS group with respect to control group. No significant differences in the cumulative daily afterdischarge duration were observed between both groups. These findings suggest that preemptive LFS can significantly decrease the incidence of hippocampus-kindled seizures and delay the progression and secondary generalization of focal seizures.

关键词： Hippocampal Rapid Kindling Epilepsy Electrical Stimulation Low-Frequency Stimulation Electrical Stimulation Protective Effect

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Hippocampal High-Frequency Stimulation Inhibites the Progression of Rapid Kindling-Induced Seizure in Rats

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Neuroscience & Medicine 2013年第2期4卷 71-76页

作者： Belen Gori Magdalena Pereyra Lucas Toibaro Carola Brescacin Gerardo Battaglia Julieta Pastorino Ariela Smigliani milagros galardi Silvia Kochen Center of Clinical and Experimental Neuroscience Epilepsy Cognition and Behavior Institute of Cellular Biology and Neuroscience “Prof. E. De Robertis” (IBCN)-National Council for Scientific and Technical Research (CONICET) School of Medicine University of Buenos Aires Buenos Aires Argentina Center of Clinical and Experimental Neuroscience Epilepsy Cognition and Behavior Institute of Cellular Biology and Neuroscience “Prof. E. De Robertis” (IBCN)-National Council for Scientific and Technical Research (CONICET) School of Medicine University of Buenos Aires Buenos Aires Argentina Laboratory of Biomedical Technology Department of Electronics Buenos Aires Faculty National Technological University (UTN) Buenos Aires Argentina.

Epilepsy is one of the most common serious neurological disorders. Pharmacoresistant epilepsy patients are poorly controlled or their seizures are refractory to drug treatment. Resective surgery is frequently a promising therapy in this population, however, not all the patients meet the eligibility criteria for the surgical treatment. Deep brain stimulation has been investigated in clinical studies and animal studies as an alternative treatment, but the optimal stimulation parameters remain an issue. The present study was designed to investigate the effect of unilateral high-frequency stimulation (HFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats, and compared the results with those of low-frequency stimulation previously published by our group. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK;n = 7) received only RK stimulus, while the treated group (HFS-hRK;n = 9) received also HFS (biphasic square wave pulses, 130 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing 78% (p 0.01) of the animals receiving HFS treatment were still not fully kindled staying in stages 0 -III (p 0.01). HFS group needed a higher number of stimulations to achieve stage III (p 0.05) with respect to control group. However, no significant differences in the cumulative daily afterdischarge duration were observed. HFS did not present significant differences compared with LFS in any of studied parameters. The findings suggest that unilateral HFS applied on hippocampus effectively inhibited the epileptogenic process induced by hippocampal rapid kindling. According to the comparative results about hippocampal rapid kindled animals stimulated with HFS and LFS (5 Hz), we found no conclusive inf

关键词： Hippocampal Rapid Kindling Epilepsy Electrical Stimulation High-Frequency Stimulation Low-Frequency Stimulation

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Characterization of the molecular dysfunctions occurring in Aicardi-Goutieres syndrome patients with mutations in ADAR1

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Genes & Diseases 2024年第3期11卷 116-119页

作者： Sofan Al wardat Loredana Frasinlli Elisa Orecchini Federica Rey Silvia Anna Ciafre Silvia galardi Jessica Garau Stella Gagliardi Simona Orcesi Davide Tonduti Stephana Carelli Cristina Cereda Ernesto Picardi Alessandro Michienzi Department of Biomedicine and Prevention University of Rome Tor VergataRome 00133Italy Pediatric Clinical Research Center"Romeo ed Enrica Invernizzi" Department of Biomedical and Clinical SciencesUniversity of MilanoMilano 20157Italy Center of Functional Genomics and Rare Diseases Department of PediatricsBuzzi Children's HospitalMilano20154Italy Department of Child Neurology and Psychiatry IRccs Mondino FoundationPavia 27100Italy Unit of Pediatric Neurology C.O.A.L.A(Center for Diagnosis and Treatment of Leukodystrophies)Buzzi Children's HospitalMilano 20154Italy Department of Biosciences Biotechnologies and EnvironmentUniversityof Bari"AldoMoro"Bari 70125Italy Institute of Biomembranes Bioenergetics and Molecular Biotechnologies(IBIOM)National Research Council(CNR)Bari 70126Italy Biostructures and Biosystems National Institute(INBB) Rome00136Italy Institute of Biochemistry and Cell Biology IBBC-CNRCampus Adriano Buzzati TraversoRome 00015Italy

Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).

关键词： ADAR1 interferon res

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