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Fibroblast growth factor\u201018 (FGF18), an important member of the fibroblast growth factor (FGF) family, has been considered a neuroprotectant with a wide range of physiological functions. However, the effects of FGF18 in HAND have not been reported previously. Here, we report that FGF18 expression was reduced in the cortex of mice challenged with HIV\u20101 Tat. Intracerebroventricular administration of FGF18 suppressed vascular inflammation in the cortex of HIV\u20101 Tat\u2010challenged mice by inhibiting VCAM\u20101 and ICAM\u20101 expression. FGF18 alleviated BBB dysfunction induced by HIV\u20101 Tat through upregulating ZO\u20101 expression. Mechanistically, FGF18 prevented HIV\u20101 Tat\u2010induced downregulation of Wnt\u20103a and \u03b2\u2010catenin. We further demonstrate that FGF18 ameliorated HIV\u20101 Tat\u2010induced cytotoxicity in bEnd.3 brain microvascular endothelial cells by reducing LDH and HMGB\u20101 release. Moreover, FGF18 protected the endothelial permeability of bEnd.3 cells and restored trans\u2010endothelial electrical resistance (TEER) in cells challenged with HIV\u20101 Tat. Consistently, FGF18 prevented the reduction of ZO\u20101 expression as well as Wnt\u20103a\/\u03b2\u2010catenin levels in bEnd.3 cells challenged with HIV\u20101 Tat. Importantly, silencing of Wnt\u20103a abrogated the beneficial effects of FGF18 in increasing ZO\u20101 expression and reducing endothelial permeability, indicating that the protective effects of FGF18 are mediated by Wnt\u20103a\/\u03b2\u2010catenin signaling. We conclude that FGF18 may serve as an effective neuroprotective agent for the treatment of HAND.<\/jats:p>","DOI":"10.1002\/ddr.70266","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:22:07Z","timestamp":1774675327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FGF18 Ameliorates HIV\u20101 Tat\u2010Induced Blood\u2010Brain Barrier Disruption via Wnt\/\u03b2\u2010Catenin Signaling"],"prefix":"10.1002","volume":"87","author":[{"given":"Pengfei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Sports and Medicine, College of Physical Education and Health Science Yibin University Yibin Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Sports and Medicine, College of Physical Education and Health Science Yibin University Yibin Sichuan 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