{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:15:12Z","timestamp":1791573312950,"version":"4.3.4"},"reference-count":97,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["NS111378"],"award-info":[{"award-number":["NS111378"]}]},{"name":"National Institute of Health","award":["NS116383"],"award-info":[{"award-number":["NS116383"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) disrupts the blood\u2013brain barrier (BBB), resulting in increased permeability, neuronal loss, and cognitive dysfunction. This study investigates the therapeutic potential of thyroid hormone (T4) to reduce BBB dysfunction following moderate fluid percussion injury. T4 injection (intraperitoneal) after TBI restores the levels of pericytes and endothelial cells vital for BBB integrity, reduces edema by downregulating AQP-4 gene expression, and enhances levels of the tight junction protein ZO-1. T4 counteracts the TBI-related increase in MMP-9 and TLR-4, significantly reducing BBB permeability. Furthermore, T4 enhances the neuroprotective functions of astrocytes by promoting the activity of A2 astrocytes. Additionally, T4 treatment increases DHA levels (important for membrane integrity and function), stimulates mitochondrial biogenesis, and leads to a notable improvement in spatial learning and memory retention. These findings suggest that T4 has significant potential to reduce vascular leakage and inflammation after TBI, thereby improving cognitive function and maintaining BBB integrity.<\/jats:p>","DOI":"10.3390\/ijms26199632","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T07:57:27Z","timestamp":1759478247000},"page":"9632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Thyroid Hormone T4 Alleviates Traumatic Brain Injury by Enhancing Blood\u2013Brain Barrier Integrity"],"prefix":"10.3390","volume":"26","author":[{"given":"Mayuri","family":"Khandelwal","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Gomez-Pinilla","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12987-016-0038-x","article-title":"Inhibition of ADAM10 Promotes the Clearance of A\u03b2 across the BBB by Reducing LRP1 Ectodomain Shedding","volume":"13","author":"Shackleton","year":"2016","journal-title":"Fluids Barriers CNS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41392-023-01481-w","article-title":"The Blood-Brain Barrier: Structure, Regulation, and Drug Delivery","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct. 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