{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T01:01:03Z","timestamp":1792285263046,"version":"4.4.0"},"reference-count":105,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:p>\n                    Pial collaterals provide protection in stroke. Evidence suggests their formation late during gestation (collaterogenesis) is driven by reduced oxygen levels in the cerebral watersheds. The purpose of this study was to determine if collaterogenesis can be re-activated in the adult to induce formation of additional collaterals (\u201cneo-collateral formation\u201d, NCF). Mice were gradually acclimated to reduced inspired oxygen (FIO\n                    <jats:sub>2<\/jats:sub>\n                    ) and maintained at 12, 10, 8.5 or 7% for two-to-eight\u2009weeks. Hypoxemia induced \u201cdose\u201d-dependent NCF and remodeling of native collaterals, and decreased infarct volume after permanent MCA occlusion. In contrast, no formation occurred of addition collateral-like intra-tree anastomoses, PComs, or branches within the MCA tree. Hypoxic NCF, remodeling and infarct protection were durable, i.e. retained for at least six\u2009weeks after return to normoxia. Hypoxia increased expression of Hif2\u03b1, Vegfa, Rabep2, Angpt2, Tie2 and Cxcr4. Neo-collateral formation was abolished in mice lacking Rabep2, a novel gene involved in VEGFA\u2192Flk1 signaling and required for formation of collaterals during development, and inhibited by knockdown of Vegfa, Flk1 and Cxcr4. Rabep2-dependent NCF was also induced by permanent MCA occlusion. This is the first report that hypoxia induces new pial collaterals to form. Hypoxia- and occlusion-induced neo-collateral formation provide models to study collaterogenesis in the adult.\n                  <\/jats:p>","DOI":"10.1177\/0271678x20924107","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T04:05:08Z","timestamp":1589861108000},"page":"1806-1822","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":64,"title":["Hypoxia induces de novo formation of cerebral collaterals and lessens the severity of ischemic stroke"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4625-1916","authenticated-orcid":false,"given":"Hua","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, McAllister Heart Institute, Curriculum in Neurobiology, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Rzechorzek","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, McAllister Heart Institute, Curriculum in Neurobiology, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Aghajanian","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, McAllister Heart Institute, Curriculum in Neurobiology, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, McAllister Heart Institute, Curriculum in Neurobiology, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"bibr1-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.010508"},{"key":"bibr2-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.08.003"},{"key":"bibr3-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.017673"},{"key":"bibr4-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.026229"},{"key":"bibr5-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.10"},{"key":"bibr6-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00070.2010"},{"key":"bibr7-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.102"},{"key":"bibr8-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.224634"},{"key":"bibr9-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302931"},{"key":"bibr10-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.014160"},{"key":"bibr11-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.03.014"},{"key":"bibr12-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.279109"},{"key":"bibr13-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.227314"},{"key":"bibr14-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.653204"},{"key":"bibr15-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-015-9465-6"},{"key":"bibr16-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17718966"},{"key":"bibr17-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-018-9655-0"},{"key":"bibr18-0271678X20924107","first-page":"333","volume":"17","author":"Mac Gabhann F","year":"2010","journal-title":"Microcirculation"},{"key":"bibr19-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12438"},{"key":"bibr20-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.07.020"},{"key":"bibr21-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1038\/nature20173"},{"issue":"1","key":"bibr22-0271678X20924107","first-page":"13291","volume":"140","author":"Aghajanian A","year":"2019","journal-title":"Circulation"},{"key":"bibr23-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-1241-1_3"},{"key":"bibr24-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.10.007"},{"key":"bibr25-0271678X20924107","unstructured":"Lambertsen CJ. Carbon dioxide tolerance and toxicity. Environmental Biomedical Stress Data Center, Institute for Environmental Medicine, University of Pennsylvania Medical Center. Philadelphia, PA. 1971, IFEM Report No. 2\u201371, https:\/\/en.wikipedia.org\/wiki\/Hypercapnia (accessed 22 April 2020)."},{"key":"bibr26-0271678X20924107","first-page":"135","volume":"59","author":"Miyamoto O","year":"2005","journal-title":"Acta Med Okayama"},{"key":"bibr27-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3023-4_30"},{"key":"bibr28-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-7411-1_5"},{"key":"bibr29-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-018-0626-y"},{"key":"bibr30-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00119.2017"},{"key":"bibr31-0271678X20924107","first-page":"1","volume":"54","author":"Risso A","year":"2014","journal-title":"Front Physiol"},{"key":"bibr32-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.10.007"},{"key":"bibr33-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2010.0198"},{"key":"bibr34-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.91"},{"key":"bibr35-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-59544-7.00005-6"},{"key":"bibr36-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1159\/000337155"},{"key":"bibr37-0271678X20924107","author":"Venkat P","year":"2017","journal-title":"Neuropharmacology"},{"key":"bibr38-0271678X20924107","author":"Bang OY","journal-title":"Transl Stroke Res"},{"key":"bibr39-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00049.2009"},{"key":"bibr40-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00929"},{"key":"bibr41-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00007.2015"},{"key":"bibr42-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.00976"},{"key":"bibr43-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.140"},{"key":"bibr44-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-91287-5_1"},{"key":"bibr45-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.812172"},{"key":"bibr46-0271678X20924107","first-page":"232","volume-title":"Collateral circulation: heart, brain, kidney, limbs","author":"Hossmann KA.","year":"1993"},{"key":"bibr47-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.06.058"},{"key":"bibr48-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c110065"},{"key":"bibr49-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092100211"},{"key":"bibr50-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.18.2.407"},{"key":"bibr51-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000259707.43496.71"},{"key":"bibr52-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2017.09.010"},{"key":"bibr53-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1159\/000353295"},{"key":"bibr54-0271678X20924107","first-page":"547","volume":"109","author":"Janda PH","year":"2009","journal-title":"J Am Osteopath Assoc"},{"key":"bibr55-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2017.09.001"},{"key":"bibr56-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.nec.2017.02.004"},{"key":"bibr57-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4675"},{"key":"bibr58-0271678X20924107","first-page":"886","volume":"24","author":"Arakawa S","year":"2003","journal-title":"Am J Neuroradiol"},{"key":"bibr59-0271678X20924107","author":"Marushima A","journal-title":"J Cereb Blood Flow Metab"},{"key":"bibr60-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.023"},{"key":"bibr61-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-91287-5_39"},{"key":"bibr62-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.3109\/10739689609148284"},{"key":"bibr63-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.558577"},{"key":"bibr64-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197703172961101"},{"key":"bibr65-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00909.2006"},{"key":"bibr66-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21523"},{"key":"bibr67-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.2174\/1570161111311050002"},{"key":"bibr68-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-1566-4_2"},{"key":"bibr69-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00451.2015"},{"key":"bibr70-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000155727.82242.e1"},{"key":"bibr71-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.3171\/2010.8.JNS091766"},{"key":"bibr72-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1148\/rg.315105014"},{"key":"bibr73-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2014-204995"},{"key":"bibr74-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2015.09.098"},{"key":"bibr75-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2017.1315499"},{"key":"bibr76-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.181115"},{"key":"bibr77-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23582"},{"key":"bibr78-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1038\/nature10144"},{"key":"bibr79-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1023\/B:HIJO.0000032355.66152.b8"},{"key":"bibr80-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1038\/382635a0"},{"key":"bibr81-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2015.02.010"},{"key":"bibr82-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1282-8"},{"key":"bibr83-0271678X20924107","first-page":"5300","volume":"17","author":"Shan C","year":"2018","journal-title":"Mol Med Rep"},{"key":"bibr84-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13032636"},{"key":"bibr85-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0039-4"},{"key":"bibr86-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.11.040"},{"key":"bibr87-0271678X20924107","first-page":"H560","volume":"259","author":"Loftus CM","year":"1990","journal-title":"Am J Physiol"},{"key":"bibr88-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.48.5.640"},{"key":"bibr89-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(86)90006-3"},{"key":"bibr90-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.35.030173.001001"},{"key":"bibr91-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.143990"},{"key":"bibr92-0271678X20924107","unstructured":"Braunwald E, Zipes DP, Libby P (eds). Heart disease. 6th ed. Philadelphia:  WB Saunders, 2001, pp.1103\u20131123."},{"key":"bibr93-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-3955(05)70125-5"},{"key":"bibr94-0271678X20924107","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.3760\/cma.j.issn.0366-6999.20140853","volume":"127","author":"Gungor H","year":"2014","journal-title":"Chin Med J"},{"key":"bibr95-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1136"},{"key":"bibr96-0271678X20924107","first-page":"A159","volume":"38","author":"Shah N","year":"2015","journal-title":"Sleep"},{"key":"bibr97-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201206-1144OC"},{"key":"bibr98-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.556746"},{"key":"bibr99-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2016.02.647"},{"key":"bibr100-0271678X20924107","first-page":"198","volume":"93","author":"Reiner L","year":"1972","journal-title":"Arch Pathol"},{"key":"bibr101-0271678X20924107","first-page":"H1031","volume":"249","author":"Scheel KW","year":"1985","journal-title":"Am J Physiol"},{"key":"bibr102-0271678X20924107","first-page":"H1667","volume":"259","author":"Scheel KW","year":"1990","journal-title":"Am J Physiol"},{"key":"bibr103-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.3.3.306"},{"key":"bibr104-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.4.6.797"},{"key":"bibr105-0271678X20924107","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.6.6.832"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X20924107","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X20924107","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X20924107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:12:56Z","timestamp":1777493576000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X20924107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,19]]},"references-count":105,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1177\/0271678X20924107"],"URL":"https:\/\/doi.org\/10.1177\/0271678x20924107","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,19]]}}}