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Expression of connexin 30 and connexin 32 in hippocampus of rat during epileptogenesis in a kindling model of epilepsy

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Neuroscience Bulletin 2012年第6期28卷 729-736页

作者： Bijan Akbarpour Mohammad Sayyah Vahab Babapour Reza Mahdian Siamak Beheshti Ahmad Reza Kamyab Departments of Physiology and Pharmacology Pasteur Institute of Iran.Tehran 131694-3551Islamic Republic of Iran Department of Physiology Faculty of Veterinary MedicineIslamic Azad UniversityScience and Research BranchTehran 14778-93855Islamic Republic of Iran Departments of Physiology and Pharmacology Pasteur Institute of IranTehran 131694-3551Islamic Republic of Iran Department of Physiology Faculty of Veterinary MedicineTehran UniversityTehran 141996-31111Islamic-Republic of Iran Department of Molecular Medicine Biotechnology Research CenterPasteur Institute of Iran Department of Biology Faculty of Science University of IsfahanIsfahan 81746-73441Islamic Republic of Iran

Objective Understanding the molecular and cellular mechanisms underlying epileptogenesis yields new in- sights into potential therapies that may ultimately prevent epilepsy. Gap junctions （GJs） create direct intercellular conduits between adjacent cells and are formed by hexameric protein subunits called connexins （Cxs）. Changes in the expression of Cxs affect GJ communication and thereby could modulate the dissemination of electrical discharges. The hippocampus is one of the main regions involved in epileptogenesis and has a wide network of GJs between different cell types where Cx30 is expressed in astrocytes and Cx32 exists in neurons and oligodendrocytes. In the present study, we evaluated the changes of Cx30 and Cx32 expression in rat hippocampus during kindling epileptogenesis. Methods Rats were stereotaxically implanted with stimulating and recording electrodes in the basolateral amygdala, which was electrically stimulated once daily at afterdischarge threshold. Expression of Cx30 and Cx32, at both the mRNA and protein levels, was measured in the hippocampus at the beginning, in the middle （after acquisition of focal seizures）, and at the end （after establishment of generalized seizures） of the kindling process, by real-time PCR and Western blot. Results Cx30 mRNA expression was upregulated at the beginning of kindling and after acquisition of focal seizures. Then it was downregulated when the animals acquired generalized seizures. Overexpression of Cx30 mRNA at the start of kindling was consistent with the respective initial protein increase. Thereafter, no change was found in protein abundance during kindling. Regarding Cx32, mRNA expression decreased after acquisition of generalized seizures and no other significant change was detected in mRNA and protein abundance during kindling. Conclusion We speculate that Cx32 GJ communication in the hip- pocampus does not contribute to kindling epileptogenesis. The Cx30 astrocytic network localized to perivascular re

关键词： connexin 30 connexin 32 hippocampus kindling

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Neuronal injury and brain-derived neurotrophic factor expression in a rat model of amygdala kindling seizures Differences in brain regions and kindling courses

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Neural Regeneration Research 2010年第8期5卷 585-590页

作者： Weihong Lin Hongmei Meng Yudan Lv Zan Wang Na Li Li Cui Baimin Zhang Department of Neurology First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

BACKGROUND：Studies have demonstrated that brain-derived neurotrophic factor （BDNF） has a dual effect on epilepsy. However, the relationship between epilepsy-induced brain injury and BDNF remains poorly ***：According to ultrastructural and molecular parameters, to detect the degree of neuronal injury and BDNF expression changes at different brain regions and different kindling times to determine the effects of BDNF on epilepsy-induced brain ***, TIME AND SETTING：A randomized, controlled, animal experiment based on neuropathology and molecular biology was performed at the Department of Physiology and Department of Pathology, Basic Medical College of Jilin University in ***：UltraSensitiveTM SP kit for immunohistochemistry （Fuzhou Maxim Biotechnology, China）, BDNF antibody （concentrated type, Wuhan Boster Biological Technology, China）, JEM-1000SX transmission electron microscopy （JEOL, Japan）, and BH-2 light microscope （Olympus, Japan） were used in the present ***：Wistar rats were randomly assigned to control （n = 6）, sham-surgery （n = 6）, and model （n = 60） groups. The control group rats were not treated; an electrode was embedded into the amygdala in rats from the sham-surgery and model groups; an amygdala kindling epilepsy model was established in the model *** OUTCOME MEASURES：Pathological changes in the temporal lobe and hippocampus were observed by light and electron microscopy at 1, 3, 7, 14, and 21 days following kindling, and BDNF expression in the various brain regions was determined by ***：In the model group, temporal lobe cortical and hippocampal neurons were swollen and the nuclei were laterally deviated. There were also some apoptotic neurons 3 days after kindling. The nucleoli disappeared and the nuclei appeared broken or lysed, as well as slight microglia hyperplasia, at 7 days. Electron microscopic observation displayed chromatin aggregation in the nuclei and slight mitochon

关键词： epilepsy brain injury brain-derived neurotrophic factor kindling brain regions rats neuronal injury neural regeneration

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

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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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“Therapeutic time window” phenomena of low-frequency stimulation at entorhinal cortex for amygdaloid-kindling seizures in rats

“Therapeutic time window” phenomena of low-frequency stimu...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Zheng-Hao XU~1 Deng-Chang WU~1 Qi FANG~1 Kai ZHONG~1 Shuang WANG~(1 2) Hong-Liu SUN~1 Shi-Hong ZHANG~1 ZhongCHEN~(1 *) 1 Institute of Neuroscience Department of Pharmacology College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China 2 Department of Neurology 2nd Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

＜正＞Objective Closed-loop stimulation mode for brain stimulation has been considered as a new option for the treatment of intractable ***,it is still unclear where and when to deliver low-frequency stimulation（LFS） in closed-loop stimulation *** present study was designed to determine whether LFS of the entorhinal cortex（EC） have anticonvulsive effect,and whether the onset of LFS given at different time points plays different *** We evaluated the effect of LFS initiated at different times after kindling stimulation on amygdaloid kindling and kindled seizures in *** Immediate and 4 s-delayed LFS initiated during AD inhibited kindling and kindled seizures,and the 4 s-delayed LFS had a stronger effect than immediate ***,neither 10 s-delayed LFS nor LFS delivered after the cessation of AD had any anticonvulsive *** the other hand,the immediate and 4 s-delayed LFS groups showed less decrease in AD threshold,and an increase in the current intensity difference between AD threshold and generalized seizure *** our results provide direct evidence that the EC is a promising target for LFS to interfere with ***,we first confirms that,even in the duration of afterdischarge,there exists a ’time window’ for LFS treatment,indicating optimization of stimulation timing is crucial for the closed-loop stimulation mode.

关键词： kindling epilepsy brain stimulation low-frequency stimulation closed-loop stimulation entorhinal cortex

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Time-and duration-dependent effect of low-frequency stimulation at different brain sites in amygdaloid-kindling rats

Time-and duration-dependent effect of low-frequency stimulat...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Deng-Chang WU~1,Zhong CHEN~(1,2,*) 1 Institute of Neuroscience,Department of Pharmacology,School of medicine,Zhejiang University,Hangzhou,310058 China 2 Department of Pharmacology,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou,310058 China

＜正＞Objective Low-frequency stimulation（LFS） has been considered as a new option for the treatment of intractable *** effect and potential mechanisms have been a topic of major clinical and scientific *** questions include which target and when to give *** Different brain targets involved in temporal epilepsy and different time points were chosen to deliver LFS in kindling ***（i） LFS of central piriform cortex,cerebellar fastigial nucleus other than kindling focus for inhibited kindling ***,LFS of tuberomammillary nucleus,the only locus of histaminergic neurons in the brain,aggravated the kindling seizures;（ii） LFS delivered immediately after the kindling stimulus rather than LFS delivered after the afterdischarge inhibited kindling seizures;and（iii） LFS delivered for 15 min and 3 min exerted different ***（i） LFS delivered to certain brain sites out of kindling focus,such as central piriform cortex cerebellar fastigial nucleus,other than kindling focus have anti-convulsive effects;（ii） LFS of different targets have different effects,there exists "negative site" for LFS treatment（such as tuberomammillary nucleus）;（iii） LFS has a aspect of time-dependent effect;（iv） LFS has a characteristics of duration-dependent effect.

关键词： epilepsy kindling low-frequency stimulation deep brain stimulation

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NRSF suppresses limbic epileptogenesis in kindling model

NRSF suppresses limbic epileptogenesis in kindling model

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Xiao-Ling HU~(1*),Xue-Wen CHEN~(1*),Lei CAI~(2*),Yang LIU~1,Jian FEI~2,Zhi-Qi XIONG~1 1 Institute of Neuroscience and Key Laboratory of Neurobiology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China 2 Laboratory of Molecular Cell Biology,Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences, Shanghai 200031,China

＜正＞Understanding epileptogenesis in molecular terms may provide clues as to how to intervene pharmacologically to prevent or cure this ***,we reported that kindling,an animal model of limbic epilepsy,increased the expression of NRSF（Neuronal repressor element-1 silencing transcription factor）,a Kuppel-type zinc-finger transcription factor and a potent silencer of neuron-specific genes in non-neuronal *** understand the functional significance of NRSF in kindling,we conditionally knocked out NRSF in the forebrain of adult mice using the Cre-loxP *** found that the development of kindling was dramatically accelerated in the knockout *** downstream NRSF target genes, including BDNF,GluR2,Na1.2,were up-regulated in the knockout mice after seizure ***,knockout NRSF abolished the anti-epileptogenic effects of the glycolytic inhibitor *** results revealed that NRSF plays a critical role in limbic epileptogenesis and is the molecular target of "ketogenic diet"（low in carbohydrates and high in fat）,an alternative therapy for drug-resistant epilepsy.

关键词： epileptogenesis NRSF kindling BDNF GluR2 Nav1.2

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Low frequency stimulation of entorhinal cortex inhibits hippocampal neuronal activities and fast kindling seizures

Low frequency stimulation of entorhinal cortex inhibits hipp...

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中国神经科学学会第十届全国学术会议

作者： Zheng-hao XU Yi WANG An-Feng TAO Ceng-Lin XU Miao-Miao JIN Kai ZHONG Shi-Hong ZHANG Zhong CHEN Zhejiang University Department of Pharmacology Key Laboratory of Medical Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of Neurobiology College of Pharmaceutical Sciences School of Medicine

Objective The entorhinal cortex（EC） is a potential target for low frequency stimulation（LFS,1Hz）treatment of temporal lobe epilepsy（TLE）.However,the neuronal basis of LFS at EC is *** on the anatomy of entorhinal-hippocampal circuit,the present study was designed to determine whether LFS at EC interfere with hippocampal neural activities and *** The effects of LFS at EC on the neural activity of dentate gyrus（DG） were examined using single-unit extracellular recordings in anesthetized rats and *** effect of LFS at EC on hippocampal fast kindling seizures was *** The spontaneous activity of the majority neurons（104/115 neurons） in DG were repeatedly interrupted as soon as LFS-on and quickly backed to baseline after *** stimulation pulse mainly induced two distinct types of neural response in DG:the commonly observed type（81/115neurons） displayed a 179±12 ms inhibition of neural firing 13±2 ms after stimulation;the second type（23/115 neurons）firstly displayed an excitatory response and then a 130±15 ms inhibition of neural firing 25±5 ms after *** effect of EC stimulation on DG neural activities were mimicked by stimulation of the main projections from the EC to DG（perforant pathway,PP） or optogenetic selective stimulation of axonal projections in *** of EC also interrupted neurons in hippocampal CA3 and CA1 but not in substantia ***,LFS of EC immediately after kindling stimulation but not after the cessation of afterdischarge interfered with kindling and kindled *** LFS of EC directly interrupted the spontaneous activity hippocampal neural activities,which may through its axonal projections to the hippocampus;and LFS of EC interferes with hippocampal fast kindling seizures in a time-dependent *** results suggest EC is a promising target for closed-loop LFS treatment of TLE.

关键词： epilepsy low-frequency stimulation entorhinal cortex kindling

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用于kindling癫癎实验的带隔离器电刺激器的设计与制造

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中国医疗器械杂志 1988年第4期 211-214页

作者： Angel R.Zapata Ferrer 墨西哥自治国立大学心理系

本文介绍一种电子装置,它被设计制造来进行特定脉宽、串长、频率和幅度特性的电刺激。用它来刺激中枢神经系统的某些区域(特定的大脑中枢和神经核)时,会产生阵发放电。为了产生电致发作,应当加以时间间隔明确规定的脉冲串1～5秒,使动物... 详细信息

本文介绍一种电子装置,它被设计制造来进行特定脉宽、串长、频率和幅度特性的电刺激。用它来刺激中枢神经系统的某些区域(特定的大脑中枢和神经核)时,会产生阵发放电。为了产生电致发作,应当加以时间间隔明确规定的脉冲串1～5秒,使动物产生一种模式的癫.这是因为被称为“点火”(Goddard等人1969年)的累进阵发激活会产生阵发性的行为改变。在癫实验领域,该系统已被用作各种实验研究.

关键词：刺激器 kindling 脉冲串电路断电器癫病方程组联立方程中国医疗器械杂志电子装置隔离电路网络模型扁桃芒果属电刺激癫痛隔离器单向器

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Talin and kindlin： the one-two punch in integrin activation

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Frontiers of Medicine 2014年第1期8卷 6-16页

作者： Feng Ye Adam K. Snider Mark H. Ginsberg Department of Medicine University of California San Diego La Jolla CA 92093 USA

Proper cell-cell and cell-matrix contacts mediated by integrin adhesion receptors are important for development, immune response, hemostasis and wound healing. Integrins pass trans-membrane signals bidirectionally through their regulated affinities for extracellular ligands and intracellular signaling molecules. Such bidirectional signaling by integrins is enabled by the conformational changes that are often linked among extracellular, transmembrane and cytoplasmic domains. Here, we review how talin-integrin and kindlin-integrin interactions, in cooperation with talin-lipid and kindlin-lipid interactions, regulate integrin affinities and how the progress in these areas helps us understand integrin-related diseases.

关键词： signal transduction transmembrane domain nanodisc integrin talin kindling cell adhesion

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