{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:30:08Z","timestamp":1786354208236,"version":"build-2736575974"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Glutamate (Glu), the primary excitatory neurotransmitter of the central and peripheral nervous systems, plays essential roles in cognition, synaptic plasticity, and immune modulation. Its dysregulation is increasingly recognized as a component of neuroinflammation and neurodegeneration in multiple sclerosis (MS). In MS and its principal experimental model, experimental autoimmune encephalomyelitis (EAE), impaired Glu homeostasis leads to excitotoxicity, calcium overload, and oxidative damage, compounded by proinflammatory mediators such as TNF-\u03b1. This makes glutamatergic receptors, transporters, and related signaling pathways candidate therapeutic targets that warrant systematic preclinical evaluation. To assess the preclinical evidence base for agents targeting these pathways, we conducted a systematic literature search, we conducted a systematic literature search and comparatively assessed published\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies examining the effects of glutamatergic agents in EAE models, applying predefined inclusion and exclusion criteria Across the reviewed EAE studies, glutamatergic agents were frequently reported to delay disease onset, alleviate clinical symptoms, attenuate neuroinflammation, and reduce demyelination, although effect sizes and reproducibility varied across models, dosing regimens and treatment timing. Collectively, these data indicate that pharmacological modulation of glutamatergic signaling can engage multiple facets of EAE pathophysiology. However, completed clinical trials of repurposed glutamatergic drugs (riluzole, amantadine, memantine, lamotrigine) have so far failed to demonstrate disease-modifying efficacy in MS, underscoring a marked translational gap.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1811323","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:42:11Z","timestamp":1786351331000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulating glutamate neurotransmission in in vivo models of Multiple Sclerosis: a narrative review"],"prefix":"10.3389","volume":"17","author":[{"given":"Eleni","family":"Stamoula","sequence":"first","affiliation":[{"name":"Department of Health Sciences, School of Life and Health Sciences, University of Nicosia","place":["UNIC Athens, Athens, 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Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoletta","family":"Floropoulou","sequence":"additional","affiliation":[{"name":"School of Medicine, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Demopoulos","sequence":"additional","affiliation":[{"name":"School of Medicine, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaella","family":"Grigoriou","sequence":"additional","affiliation":[{"name":"School of Medicine, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Melnikov","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunology, Federal Center of Brain Research and Neurotechnologies of the Federal Medical-Biological Agency of 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