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In contrast to traditional reviews focusing on biochemistry, this work summarizes the structural and mechanical properties of major ECM subtypes, and illustrates how mechanical and biochemical signals jointly regulate glial activity via key mechanosensitive pathways. Glia in turn dynamically remodel ECM, forming a reciprocal regulatory network. This paper also analyzes characteristic mechanical disorders in Alzheimer\u2019s disease, multiple sclerosis and traumatic brain injury, and addresses targeted therapeutic strategies. Current research challenges and emerging interdisciplinary directions are also discussed. This review provides a valuable reference for exploring neurological disease mechanisms and developing new therapies.<\/jats:p>","DOI":"10.3390\/cells15141268","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:29:39Z","timestamp":1784100579000},"page":"1268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Basis of Glia\u2013ECM Interplay in Central Nervous System Homeostasis and Plasticity"],"prefix":"10.3390","volume":"15","author":[{"given":"Lanlan","family":"Wang","sequence":"first","affiliation":[{"name":"College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghong","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-7533","authenticated-orcid":false,"given":"Mi","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-3056","authenticated-orcid":false,"given":"Zenghui","family":"Yue","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-7332","authenticated-orcid":false,"given":"Rong","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuron.2017.07.030","article-title":"The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease","volume":"96","author":"Iadecola","year":"2017","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s43556-026-00415-6","article-title":"The extracellular matrix in inflammation and cancer","volume":"7","author":"Zhang","year":"2026","journal-title":"Mol. 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