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These synapses, due to the inactivity of AMPA receptors under pathological conditions, are unable to efficiently transmit neural signals, leading to disrupted neural communication. This dysfunction is particularly influenced by chronic inflammation, alterations in neurotransmitter dynamics, and a reduction in neurotrophic factors in MS patients. One of the key aspects of understanding silent synapses is that they not only have the potential for reactivation, but they can also contribute to the restoration of neural networks by re\u2010establishing neuroplasticity. Recent research has shown that targeted treatments, including activating NMDA receptors, increasing brain\u2010derived neurotrophic factor (BDNF), and using drugs like ketamine, help restore patients\u2019 cognitive function. Apart from pharmacological therapies, non\u2010pharmacological strategies also include cognitive rehabilitation, physical activity, and noninvasive brain stimulation, which might promote synaptic plasticity and consequently quality of life. Therefore, reactivating latent synapses as a novel and interesting therapy strategy could not only improve cognitive performance in MS patients but also open the road for fresh methods to mend the nervous system and increase their quality of life. Though its specific form has not yet been thoroughly investigated, this approach offers great promise to become a viable MS treatment.<\/jats:p>","DOI":"10.1002\/dneu.23014","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T06:36:28Z","timestamp":1761287788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Silent Synapses in Multiple Sclerosis: From Synaptic Dysfunction to Reactivation\u2010Based Therapies\u2014A Narrative Review of Cognitive and Neuroplasticity Outcomes"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8963-8398","authenticated-orcid":false,"given":"Zinab","family":"Alatawi","sequence":"first","affiliation":[{"name":"Department of Family and Community Medicine, Faculty of Medicine University of Tabuk, Tabuk 47512 Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6635084"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac471"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800946105"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00740-6"},{"key":"e_1_2_13_6_1","unstructured":"Akbar I2025. \u201cMolecular and Cellular Regulation of Inflammatory T Cell Function in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.\u201d PhD diss. 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