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β2-Microglobulin exacerbates neuroinflammation,brain damage,and cognitive impairment after stroke in rats

Neural Regeneration Research 2023年第3期18卷 603-608页

作者： Feng Chen Jing Liu Fa-Qiang Li Shuai-Shuai Wang Yan-Yan Zhang Yun-Yun Lu Fang-Fang Hu Rui-Qin Yao Department of Neurology Xuzhou Cancer HospitalXuzhouJiangsu ProvinceChina Department of Neurobiology Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Xuzhou No.1 People’s Hospitalthe Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s *** upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly *** this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral *** found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery *** interference was used to inhibitβ2M expression in the acute period of cerebral *** staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,***,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M *** findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

关键词： cognitive impairment cognitive improvement glial activation infarct volume ischemia middle cerebral artery occlusion neuroinflammation NLRP3 inflammasome stroke β2 microglobulin

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cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2016年第7期17卷 503-514页

作者： Pan XU Shu-ping XU Ke-zhu WANG Cong LU Hong-xia ZHANG Rui-le PAN Chang QI Yan-yan YANG Ying-hui LI Xin-min LIU Research Center of Pharmacology and Toxicology Institute of Medicinal Plant Development (IMPLAD)Chinese Academy of Medical Sciences and Peking Union Medical College Division of Stem Cell Regulation and Application Hunan University of Chinese Medicine Science and Technology on Human Factors Engineering Laboratory Astronaut Centre of China

Objectives： The aim of the study is to evaluate the cognitive-enhancing effects of hydrolysate of polyga- lasaponin （HPS） on senescence accelerate mouse P8 （SAMP8） mice, an effective Alzheimer＇s disease （AD） model, and to research the relevant mechanisms. Methods： The cognitive-enhancing effects of HPS on SAMP8 mice were assessed using Morris water maze （MWM） and step-through passive avoidance tests. Then N-methyl-D-aspartate （NMDA） receptor subunit expression for both the cortex and hippocampus of mice was observed using Western blot- ting. Results： HPS （25 and 50 mg/kg） improved the escape rate and decreased the escape latency and time spent in the target quadrant for the SAMP8 mice in the MWM after oral administration of HPS for 10 d. Moreover, it decreased error times in the passive avoidance tests. Western blotting showed that HPS was able to reverse the levels of NMDAR1 and NMDAR2B expression in the cortex or hippocampus of model mice. Conclusions： The present study suggested that HPS can improve cognitive deficits in SAMP8 mice, and this mechanism might be associated with NMDA receptor （NMDAR）-related pathways.

关键词： cognitive improvement Hydrolysate of polygalasaponin SAMP8 mice

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Coassembly of Macrocyclic Amphiphiles for Anti-β-Amyloid Therapy of Alzheimer’s Disease

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CCS Chemistry 2021年第9期3卷 2485-2497页

作者： Yu-Chen Pan Hui Wang Xinxin Xu Han-Wen Tian Hong Zhao Xin-Yue Hu Yu Zhao Yang Liu Guihua Ding Qingbin Meng Bart Jan Ravoo Tao Zhang Dong-Sheng Guo College of Chemistry Key Laboratory of Functional Polymer MaterialsMinistry of EducationState Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071 College of Life Sciences Key Laboratory of Bioactive MaterialsMinistry of EducationNankai UniversityTianjin 300071 College of Chemistry Key Laboratory of Functional Polymer Materials(Ministry of EducationState Key Laboratory of Medicinal Chemical Biology)Nankai UniversityTianjin 300071 State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850 Organic Chemistry Institute and Center for Soft Nanoscience(SoN) Westfälische Wilhelms-Universität MünsterMünster 48149

Based on the amyloid hypothesis,anti-β-amyloid(Aβ)therapy has dominated clinical trials for the prevention and treatment of Alzheimer’s disease(AD)in recent years.A key element of this strategy is the interaction between therapeutic agents and Aβ.However,the design and development of artificial receptors that may render selective and strong recognition toward Aβremains a huge challenge because of the complexity and size of peptide guests and their flexible conformation.

关键词： macrocyclic amphiphile heteromultivalent recognition fibril disintegration cognitive improvement Alzheimer’s disease

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Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

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Neuroprotection 2024年第1期2卷 16-32页

作者： Yang Zhu Lingyi Liao Shihao Gao Yong Tao Hao Huang Xiangqin Fang Changyan Yuan Changyue Gao Department of Rehabilitation Medicine Daping HospitalArmy Medical UniversityChongqingChina Department of Rehabilitation Medicine General Hospitalof SouthernTheatre Command of PLAGuangzhouChina

Alzheimer's disease(AD)is a prevalent neurodegenerative disorder characterized by gradual deterioration of cognitive functions,for which an effective treatment is currently *** transcranial magnetic stimulation(rTMS),a well-established noninvasive brain stimulation method,is utilized in clinical settings to address various neuropsychiatric conditions,such as depression,neuropathic pain,and poststroke *** evidence suggests that rTMs may enhance cognitive abilities in individuals with ***,its optimal therapeutic protocols and precise mechanisms are currently unknown,impeding its clinical *** the present review,we aimed to summarize and discuss the efficacy-related parameters in rTMs treatment,encompassing stimulus frequency,stimulus pattern,stimulus intensity,and the configuration of the stimulus ***,we reviewed promising rTMS therapeutic protocols involving various combinations of these factors,that were examined in clinical *** on our analysis,we propose that a multisite high-frequency rTMS(HF-rTMS)regimen has value in AD therapy,and that promising single-site protocols,such as HF-rTMS,applied over the left dorsolateral prefrontal cortex,precuneus,or cerebellum are required to be validated in larger clinical ***,we provide a comprehensive review of the potential mechanisms underlying the neuroprotective effects of rTMS on cognition in AD in terms of brain network modulation as well as cellular and molecular *** conclusion,the interaction of diverse mechanisms may be responsible for the total therapeutic effect of rTMS on *** review provides theoretical and practical evidence for the future clinical application and scientific research of rTMS in AD.

关键词： Alzheimer's disease cognitive improvement molecular mechanism neuroprotection repetitive transcranial magnetic stimulation synaptic plasticity

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