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Pericytes and endothelial cells of the neurovascular unit (NVU) function collectively to maintain strict regulation of the BBB through tight junctions. Secondary injury mechanisms, such as pro-angiogenic signals that contribute to pericyte loss, can prolong and exacerbate primary vascular injury. Human umbilical cord perivascular cells (HUCPVCs) are a source of mesenchymal stromal cells (MSCs) that have been shown to reduce vascular dysfunction after neurotrauma. We hypothesized that the perivascular properties of HUCPVCs can reduce vascular dysfunction after modeled TBI by preserving the pericyte\u2013endothelial interactions. Rats were subjected to a moderate fluid percussion injury (FPI) and intravenously infused with 1,500,000 HUCPVCs post-injury. At acute time points (24\u2009h and 48\u2009h) quantitative polymerase chain reaction (qPCR) analysis demonstrated that the gene expression of angiopoietin-2 was increased with FPI and reduced with HUCPVCs. Immunofluorescent assessment of RECA-1 (endothelial cells) and platelet-derived growth factor receptors (PDGFR-\u03b2) (pericytes) revealed that capillary and pericyte densities as well as the co-localization of the two cells were decreased with FPI and preserved with HUCPVC administration. These acute HUCPVC-mediated protective effects were associated with less permeability to Evan's blue dye and increased expression of the tight junction occludin, suggesting less vascular leakage. Further, at 4 weeks post-injury, HUCPVC administration was associated with reduced anxiety and decreased \u03b2-amyloid precursor protein (\u03b2-APP) accumulation. In summary, HUCPVCs promoted pericyte\u2013endothelial barrier function that was associated with improved long-term outcome.<\/jats:p>","DOI":"10.1089\/neu.2021.0158","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T05:35:54Z","timestamp":1619242554000},"page":"2747-2762","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Vascular Dysfunction after Modeled Traumatic Brain Injury Is Preserved with Administration of Umbilical Cord Derived Mesenchymal Stromal Cells and Is Associated with Modulation of the Angiogenic Response"],"prefix":"10.1177","volume":"38","author":[{"given":"Tanya A.","family":"Barretto","sequence":"first","affiliation":[{"name":"Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada."},{"name":"Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Park","sequence":"additional","affiliation":[{"name":"Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Telliyan","sequence":"additional","affiliation":[{"name":"Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Liu","sequence":"additional","affiliation":[{"name":"Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Gallagher","sequence":"additional","affiliation":[{"name":"CReATe Fertility Centre, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford","family":"Librach","sequence":"additional","affiliation":[{"name":"CReATe Fertility Centre, Toronto, Ontario, Canada."},{"name":"Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada."},{"name":"Department of Physiology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Baker","sequence":"additional","affiliation":[{"name":"Keenan Research Centre, St. Michaels's Hospital, Toronto, Ontario, Canada."},{"name":"Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada."},{"name":"Department of Critical Care, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada."},{"name":"Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-014-9557-x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13165"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-015-9651-7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23300"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20126"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000248"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23732"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4288"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.60"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox058"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01472-08"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0914-18.2018"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2018.06.001"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.03.014"},{"key":"e_1_3_4_16_2","first-page":"S63","article-title":"Blood\u2013brain barrier disruption following traumatic brain injury: roles of tight junction proteins","volume":"32","author":"Ng I.","year":"2003","unstructured":"Ng I., , Yap E., , Tan W.L., , and Kong N.Y. 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