An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patien...Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.展开更多
背景:相比于常规重复经颅磁刺激,Theta爆发式经颅磁刺激因具有刺激时间短、效率高、安全性好和效果持久等优势,正受到各领域学者的广泛关注,研究热度持续上升。目的:通过对近20年国际Theta爆发式经颅磁刺激研究进行文献计量学的可视化分...背景:相比于常规重复经颅磁刺激,Theta爆发式经颅磁刺激因具有刺激时间短、效率高、安全性好和效果持久等优势,正受到各领域学者的广泛关注,研究热度持续上升。目的:通过对近20年国际Theta爆发式经颅磁刺激研究进行文献计量学的可视化分析,梳理Theta爆发式经颅磁刺激研究的发展脉络,总结研究现状,揭示研究热点和发展趋势,为后续研究提供借鉴和参考。方法:检索Web of Science核心集数据库中2005年1月至2024年6月有关Theta爆发式经颅磁刺激的相关文献,应用CiteSpace软件进行年度发文量分析,国家、机构和作者合作共现分析,参考文献、期刊和作者共被引分析,关键词共现、聚类、时间演化和突现分析等,并绘制可视化知识图谱。结果与结论:①共纳入1914篇文献,近20年Theta爆发式经颅磁刺激研究量呈总体上升趋势,预计未来将继续保持研究热度。②发文量前3位的国家为美国、中国和意大利,机构为加拿大多伦多大学、英国伦敦大学和美国哈佛大学医学院;美国哈佛大学医学院的Pascual-leone,Alvaro研究成果最多,中国长庚大学的HUANG YZ被引频次最高;《NEURON》为影响力最大的期刊。③高频关键词、高被引文献和聚类主题结果显示,近20年Theta爆发式经颅磁刺激研究热点主要集中于:Theta爆发式经颅磁刺激对突触可塑性和神经生理活动的作用机制,Theta爆发式经颅磁刺激刺激不同脑区靶点的作用效果(包括运动皮质、背外侧前额叶皮质、前扣带皮质和小脑等),以及Theta爆发式经颅磁刺激对神经和精神疾病的疗效探讨(包括抑郁症、帕金森病运动障碍、脑卒中后运动障碍和认知障碍,以及阿尔茨海默病记忆障碍等)。此外,综述和临床试验类文献被引频次最高,未来可重点关注。④关键词突现、文献突现和关键词时间演化分析显示,“重度抑郁症、应用指南、评定量表、疗效、障碍、难治性抑郁症、Meta分析”等不仅是当前的研究热点,也是未来的研究趋势。⑤未来,Theta爆发式经颅磁刺激研究应加强核心作者和机构的区域性合作,发掘其在临床难治性疾病中的应用,通过结合前沿技术和优化刺激参数,实现Theta爆发式经颅磁刺激应用的精准化、个性化和最优化,解决更多临床难题。展开更多
Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the...Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.展开更多
Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety...Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety patients with PSEI who were hospitalized in the rehabilitation department of Xuzhou Central Hospital and Xuzhou Rehabilitation Hospital from April 2021 to June 2022 were selected and divided into iTBS group,high‑frequency group and control group.All three groups of patients received routine rehabilitation training,given rTMS treatment with iTBS,10 Hz and shame stimulation for 4 weeks.Before and after treatment,all the patients were evaluated with the Montreal cognitive assessment(MoCA),the frontal assessment battery(FAB),troop color‑word test(SCWT),shape trails test(STT),digit span test(DST)and event related potential P300.Results:After treatment,MoCA,FAB,SCWT,STT,DST scores,P300 latency and amplitude were significantly better in the three groups than before treatment(P<0.05).MoCA,FAB,SCWT,STT‑B,DST scores,P300 latency and amplitude in the iTBS group and high‑frequency group were better than in the control group,with significant differences(P<0.05).The difference between iTBS group and high‑frequency group was not statistically significant(P>0.05).Conclusion:iTBS can improve PSEI,and the efficacy is comparable to 10Hz rTMS.iTBS takes less time with better efficiency,and it is worth popularizing and applying in clinic.展开更多
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金supported by National Key R&D Program of China,No.2020YFC2004202the National Natural Science Foundation of China,Nos.81974358 and 81772453(all to DSX).
文摘Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.
文摘背景:相比于常规重复经颅磁刺激,Theta爆发式经颅磁刺激因具有刺激时间短、效率高、安全性好和效果持久等优势,正受到各领域学者的广泛关注,研究热度持续上升。目的:通过对近20年国际Theta爆发式经颅磁刺激研究进行文献计量学的可视化分析,梳理Theta爆发式经颅磁刺激研究的发展脉络,总结研究现状,揭示研究热点和发展趋势,为后续研究提供借鉴和参考。方法:检索Web of Science核心集数据库中2005年1月至2024年6月有关Theta爆发式经颅磁刺激的相关文献,应用CiteSpace软件进行年度发文量分析,国家、机构和作者合作共现分析,参考文献、期刊和作者共被引分析,关键词共现、聚类、时间演化和突现分析等,并绘制可视化知识图谱。结果与结论:①共纳入1914篇文献,近20年Theta爆发式经颅磁刺激研究量呈总体上升趋势,预计未来将继续保持研究热度。②发文量前3位的国家为美国、中国和意大利,机构为加拿大多伦多大学、英国伦敦大学和美国哈佛大学医学院;美国哈佛大学医学院的Pascual-leone,Alvaro研究成果最多,中国长庚大学的HUANG YZ被引频次最高;《NEURON》为影响力最大的期刊。③高频关键词、高被引文献和聚类主题结果显示,近20年Theta爆发式经颅磁刺激研究热点主要集中于:Theta爆发式经颅磁刺激对突触可塑性和神经生理活动的作用机制,Theta爆发式经颅磁刺激刺激不同脑区靶点的作用效果(包括运动皮质、背外侧前额叶皮质、前扣带皮质和小脑等),以及Theta爆发式经颅磁刺激对神经和精神疾病的疗效探讨(包括抑郁症、帕金森病运动障碍、脑卒中后运动障碍和认知障碍,以及阿尔茨海默病记忆障碍等)。此外,综述和临床试验类文献被引频次最高,未来可重点关注。④关键词突现、文献突现和关键词时间演化分析显示,“重度抑郁症、应用指南、评定量表、疗效、障碍、难治性抑郁症、Meta分析”等不仅是当前的研究热点,也是未来的研究趋势。⑤未来,Theta爆发式经颅磁刺激研究应加强核心作者和机构的区域性合作,发掘其在临床难治性疾病中的应用,通过结合前沿技术和优化刺激参数,实现Theta爆发式经颅磁刺激应用的精准化、个性化和最优化,解决更多临床难题。
基金supported by the National Natural Science Foundation of China(81901142)funds for key support objects of Third Military Medical University.
文摘Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
基金Research project of Jiangsu Provincial Health Commission(No.K2019012)Xuzhou Science and Technology Bureau planned project(No.KC19156)。
文摘Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety patients with PSEI who were hospitalized in the rehabilitation department of Xuzhou Central Hospital and Xuzhou Rehabilitation Hospital from April 2021 to June 2022 were selected and divided into iTBS group,high‑frequency group and control group.All three groups of patients received routine rehabilitation training,given rTMS treatment with iTBS,10 Hz and shame stimulation for 4 weeks.Before and after treatment,all the patients were evaluated with the Montreal cognitive assessment(MoCA),the frontal assessment battery(FAB),troop color‑word test(SCWT),shape trails test(STT),digit span test(DST)and event related potential P300.Results:After treatment,MoCA,FAB,SCWT,STT,DST scores,P300 latency and amplitude were significantly better in the three groups than before treatment(P<0.05).MoCA,FAB,SCWT,STT‑B,DST scores,P300 latency and amplitude in the iTBS group and high‑frequency group were better than in the control group,with significant differences(P<0.05).The difference between iTBS group and high‑frequency group was not statistically significant(P>0.05).Conclusion:iTBS can improve PSEI,and the efficacy is comparable to 10Hz rTMS.iTBS takes less time with better efficiency,and it is worth popularizing and applying in clinic.
