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Through detailed analysis of plasma samples obtained from a large number of healthy volunteers (<jats:italic>n<\/jats:italic>\u2009=\u200990) and ischemic stroke patients (<jats:italic>n<\/jats:italic>\u2009=\u200981), the current study found significant elevations in the levels of TNF-\u03b1 at baseline (within the first 48\u00a0h of stroke) and on days 7, 30, 90 after ischaemic stroke. It then assessed the impact of this inflammatory cytokine on an <jats:italic>in<\/jats:italic><jats:italic>vitro<\/jats:italic> model of human blood\u2013brain barrier (BBB) and revealed dramatic impairments in both barrier integrity and function, the main cause of early death after an ischemic stroke. Co-treatment of BBB models in similar experiments with outgrowth endothelial cell-derived conditioned media (OEC-CM) negated the deleterious effects of TNF-\u03b1 on BBB. Effective suppression of anti-angiogenic factor endostatin, stress fiber formation, oxidative stress, and apoptosis along with concomitant improvements in extracellular matrix adhesive and tubulogenic properties of brain microvascular endothelial cells and OECs played an important role in OEC-CM-mediated benefits. Significant increases in pro-angiogenic endothelin-1 and monocyte chemoattractant protein-1 in OEC-CM compared to the secretomes of OEC and HBMEC, detected by proteome profiling assay, accentuate the beneficial effects of OEC-CM. In conclusion, this reverse translational study identifies TNF-\u03b1 as an important mediator of post-ischemic cerebral barrier damage and proposes OEC-CM as a potential vasculoprotective therapeutic strategy by demonstrating its ability to regulate a wide range of mechanisms associated with BBB function. Clinical trial registration NCT02980354.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s12015-022-10439-4","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T19:02:31Z","timestamp":1662145351000},"page":"503-515","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Outgrowth Endothelial Cell Conditioned Medium Negates TNF-\u03b1-Evoked Cerebral Barrier Damage: A Reverse Translational Research to Explore Mechanisms"],"prefix":"10.1007","volume":"19","author":[{"given":"Rais Reskiawan A.","family":"Kadir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mansour","family":"Alwjwaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamini","family":"Rakkar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Othman Ahmad","family":"Othman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"Sprigg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip M.","family":"Bath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-0237","authenticated-orcid":false,"given":"Ulvi","family":"Bayraktutan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"issue":"10159","key":"10439_CR1","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","volume":"392","author":"GA Roth","year":"2018","unstructured":"Roth, G. 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