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Despite extreme plasticity of neurosensory structures, the capacity to reconcile barrier phenotype of the microcirculation with an angiogenic cascade is not known. Here we provide primary evidence for such a response in an elemental neurosensory structure, human dental pulp, following chronic carious insult. In response to hypoxic challenge neurosensory odontoblasts express hypoxia\u2010inducible factor\u20101\u03b1 and notch\u20101. Associated radial rearrangement of astrocyte\u2010like telacytes that communicate through a cell\u2010poor zone with the microvasculature is observed. Activated pericytes characterized by expression of \u03b1\u2010smooth muscle actin are located adjacent to the telacyte attachment to the vasculature. In this location, endothelial expression of sonic hedgehog parallels expression of notch\u20101 by pericytes. The angiogenic response is initiated by pericyte contraction and altered endothelial polarity and proliferation leading to intussusception of endothelial cells and extensive remodeling of basement membrane with upregulation of laminin\u20108 and laminin\u20105. These responses guide intravascular loop formation that maintains both intact basement membrane and tight junctions. This initial phase is followed by formation of anastomoses that enhance the hemodynamic capacity of the intravascular loops. The formation of anastomoses is mediated by extension of cytonemes from pericytes guided by MHC\u2010II<jats:sup>+<\/jats:sup>\/CD\u2010163<jats:sup>+<\/jats:sup> microglia aligned with the telacytes. The cytonemes seek out pericytes on adjacent intravascular loops to initiate migration of endothelial cells. These findings support a new paradigm for understanding angiogenic capacity of neurosensory structures and aberrations of this response manifest as neurovasculopathies. J. Comp. Neurol. 520:3803\u20133826, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.23162","type":"journal-article","created":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T06:46:15Z","timestamp":1339137975000},"page":"3803-3826","source":"Crossref","is-referenced-by-count":22,"title":["Directed glia\u2010assisted angiogenesis in a mature neurosensory structure: Pericytes mediate an adaptive response in human dental pulp that maintains blood\u2010barrier function"],"prefix":"10.1002","volume":"520","author":[{"given":"Ramin M.","family":"Farahani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Sarrafpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Simonian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601020200"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1439-0264.1999.00195.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09522"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.106.095042"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1017929124317"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.14.5568"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20642"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2004.03.022"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/74651"},{"key":"e_1_2_10_13_1","first-page":"1201","article-title":"The effect of oxygen on vasoformative cell division. 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