{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:28:53Z","timestamp":1793305733434,"version":"4.5.0"},"reference-count":129,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    Stroke and Alzheimer\u2019s disease are common neurological disorders and often occur in the same individuals. The comorbidity of the two neurological disorders represents a grave health threat to older populations. This review presents a brief background of the development of novel concepts and their clinical potentials. The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx is critical for neuronal function. An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mainly via N-methyl-D-aspartate receptors, particularly of those at the extrasynaptic site. This Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity. Furthermore, mild but sustained Ca\n                    <jats:sup>2+<\/jats:sup>\n                    increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer\u2019s disease are not immediately toxic, but gradually set off deteriorating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways. Based on the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    hypothesis of Alzheimer\u2019s disease and recent advances, this Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated \u201csilent\u201d degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis. The 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 excitotoxicity. Ischemic stroke and Alzheimer\u2019s disease, therefore, share an N-methyl-D-aspartate receptor- and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -mediated mechanism, although with much different time courses. It is thus proposed that early interventions to control Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer\u2019s disease and Alzheimer\u2019s disease-related dementia. This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-24-00398","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T09:02:27Z","timestamp":1722848547000},"page":"1981-1988","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer\u2019s disease"],"prefix":"10.4103","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1335-1398","authenticated-orcid":false,"given":"Shan Ping","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA"},{"name":"Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Q.","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA"},{"name":"Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, 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