Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

作     者：Shan Ping Yu Emily Choi Michael QJiang Ling Wei 

作者机构：Department of AnesthesiologyEmory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive RehabilitationAtlanta Veterans Affairs Medical CenterDecaturGAUSA 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2025年第20卷第7期

页      面：1981-1988页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by National Health Institute(NIH)grant NS099596(to LW and SPY),NS114221(to LW and SPY) Veterans Affair(VA)SPiRE grant RX003865(to SPY) supported by the O.Wayne Rollins Endowment Fund(to SPY) John E.Steinhaus Endowment Fund(to LW) 

主　　题：Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment 

摘      要：Stroke and Alzheimer s disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer s disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer s disease and recent advances,this Ca^(2+)-activated“silentdegenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer s disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer s disease and Alzheimer s disease-related