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As blood vessels in the spinal cord are reported to have distinct properties from those in the brain, here we examined the impact of \u03b21 integrin inhibition on spinal cord vascular integrity, both under normoxic conditions, when blood vessels are stable, and during exposure to chronic mild hypoxia (CMH), when extensive vascular remodeling occurs. We found that a function-blocking \u03b21 integrin antibody triggered a small degree of vascular disruption in the spinal cord under normoxic conditions, but under hypoxic conditions, it greatly enhanced (20-fold) vascular disruption, preferentially in spinal cord white matter (WM). This resulted in elevated microglial activation as well as marked loss of myelin integrity and reduced density of oligodendroglial cells. To understand why vascular breakdown is localized to WM, we compared expression levels of major BBB components of WM and grey matter (GM) blood vessels, but this revealed no obvious differences. Interestingly however, hypoxyprobe staining demonstrated that the most severe levels of spinal cord hypoxia induced by CMH occurred in the WM. Analysis of brain tissue revealed a similar preferential vulnerability of WM tracts to show vascular disruption under these conditions. Taken together, these findings demonstrate an essential role for \u03b21 integrins in maintaining vascular integrity in the spinal cord, and unexpectedly, reveal a novel and fundamental difference between WM and GM blood vessels in their dependence on \u03b21 integrin function during hypoxic exposure. Our data support the concept that the preferential WM vulnerability described may be less a result of intrinsic differences in vascular barrier properties between WM and GM, and more a consequence of differences in vascular density and architecture.<\/jats:p>","DOI":"10.1186\/s40478-024-01749-4","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T11:02:03Z","timestamp":1710932523000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["\u03b21 integrins play a critical role maintaining vascular integrity in the hypoxic spinal cord, particularly in white matter"],"prefix":"10.1186","volume":"12","author":[{"given":"Sebok K.","family":"Halder","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun","family":"Sapkota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-3609","authenticated-orcid":false,"given":"Richard","family":"Milner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"1749_CR1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1038\/bjc.1995.429","volume":"72","author":"GE Arteel","year":"1995","unstructured":"Arteel GE, Thurman RG, Yates JM, Raleigh JA (1995) Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver. 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