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low-frequency stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy

Neuroscience Bulletin 2024年第5期40卷 564-576页

作者： Yujia Shen Yiwei Gong Xiaoli Da Shajing Gao Shuo Zhang Minjuan Sun Yuanzhi Yang Xiaoyun Qiu Menghan Li Yang Zheng Fan Fei Yi Wang Zhong Chen Cenglin Xu Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou310053China Institute of Pharmacology and Toxicology NHC and CAMS Key Laboratory of Medical NeurobiologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Department of Neurology First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310003China Department of Pharmacy The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310003China

Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary *** is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective ***,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse ***,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling *** kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive *** at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary *** application along with the primary epileptogenesis was ***,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary *** results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.

关键词： Secondary epileptogenesis low-frequency stimulation Subiculum Temporal lobe epilepsy

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low-frequency stimulation inhibits epileptogenesis by modulating the early network of the limbic system as evaluated in amygdala kindling model

Low-frequency stimulation inhibits epileptogenesis by modula...

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中国神经科学学会第十届全国学术会议

作者： Yi WANG Zhenghao XU Hui CHENG Yi GUO Cenglin XU Shuang WANG Jianmin ZHANG Meiping DING Zhong CHEN Department of Pharmacology Key Laboratory of Medical Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of NeurobiologyCollege of Pharmaceutical SciencesSchool of MedicineZhejiang University Epilepsy Center Department of NeurologySecond Affiliated HospitalSchool of MedicineZhejiang University

Objective low-frequency stimulation(LFS) is emerging as a new option for the treatment of *** present study was designed to determine whether there is a crucial period for the treatment of epileptogenesis with *** LFS was dehvered at different time-points to evaluate its anti-epileptogenic effect in amygdala-kindling rats.F-fluorodeoxyglucose small-animal positron-emission tomography(microPET) and multi-channel EEG recording(MER) were used to investigate the dynamics of brain networks during epileptogenesis and LFS *** Interestingly,LFS delivered in the first 7 days significantly retarded the progression of behavioral seizure stages and shortened the afterdischarge duration(ADD),LFS delivered throughout the whole process resulted in similar ***,if LFS was delivered at the beginning of seizure stage 2 or 3(5 ± 0.3 days during kindling acquisition),it had no anti-epileptogenic effect and even prolonged the ADD and enhanced synchronization of the *** study revealed a notable hypometabolism in the amygdala,piriform cortex,entorhinal cortex and other regions in the limbic system during the period from seizure stage 0 to stage 2 or *** glucose metabolism in those regions was specifically increased by *** further verified that an early network of afterdischarge spread was formed in those brain regions during kindling *** Thus,we provided direct evidence that modulation of the early network in the limbic system is crucial for the anti-epileptogenic effect of LFS in amygdaloid-kindling rats.

关键词： brain stimulation low-frequency stimulation epileptogenesis early network microPET

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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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“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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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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Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

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Neural Regeneration Research 2016年第10期11卷 1584-1590页

作者： Jiang Li Xiang-min Meng Ru-yi Li Ru Zhang Zheng Zhang Yi-feng Du Shandong Provincial Hospital of Shandong University Jinan Shandong Province China Affiliated Hospital of Qingdao University Qingdao Shandong Province China

Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex （M1）. The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

关键词： nerve regeneration brain injury repetitive transcranial magnetic stimulation cerebral infarction low-frequency stimulation high-frequency stimulation upper-limb motor function cerebral cortex stroke rehabilitation motor-evoked potential central motor conductiontime primary motor cortex neuroplasticity neural reorganization neural regeneration

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校近期发表IF≥4.0的SCI论文摘要--Metaplastic Regulation of Long-Term Potentiation/Long-Term Depression Threshold by Activity-Dependent Changes of NR2A/NR2B Ratio

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南京医科大学学报（自然科学版） 2009年第10期29卷 1379-1379页

作者： Xu Zhuo Chen Rong-Qing Gu Qin-Hua Yan Jing-Zhi Wang Shan-Hui Liu Su-Yi Lu Wei Nanjing Med Univ Dept Neurobiol Nanjing 210029 Jiangsu Prov Peoples R China 9 Neurodegenerat Dis Jiangsu Prov Nanjing 210029 Jiangsu Prov Peoples R China Nanjing Med Univ Lab Reprod Med Nanjing 210029 Jiangsu Prov Peoples R China Nanjing Med Univ Key Lab Human Funct Genom Jiangsu Prov Nanjing 210029 Jiangsu Prov Peoples R China

In vivo experience induces changes in synaptic NMDA receptor (NMDAR) subunit components, which are correlated with subsequent modifications of synaptic plasticity. However, little is known about how these subunit changes regulate the induction threshoht of subsequent plasticity. At hippocampal Schaffer collateral-CA1 synapses, we first examined whether a recent history of neuronal activity could affect subsequent synaptic plasticity through its actions on NMDAR subunit components. We found that prior activity history produced by priming stimulations (PSs) across a wide range of frequencies (1-100 Hz) could induce bidirectional changes in the NR2A/NR2B ratio, which governs the threshold for subsequent long-term potentiation/long-term depression (LTP/ LTD). Manipulating the NR2A/NR2B ratio through partial NR2 subunit blockade mimicked the PS regulation of the LTP/LTD threshold. Our results demonstrate that activity-dependent changes in the NR2A/NR2B ratio can be critical factors in metaplastic regulation of the LTP/LTD threshold.

关键词： receptor subunit composition bidirectional synaptic plasticity low-frequency stimulation visual-cortex nmda receptors ampa receptor in-vivo hp hippocampus experience

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