{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:38:27Z","timestamp":1790620707359,"version":"4.1.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:p>The myoblast-mediated delivery of angiogenic genes represents a cell-based approach for targeted induction of therapeutic collateralization. Here, we tested the superiority of myoblast-mediated co-delivery of vascular endothelial growth factor-A (VEGF) together with platelet-derived growth factor-BB (PDGF-BB) on transpial collateralization of an indirect encephalomyosynangiosis (EMS) in a model of chronic cerebral ischemia. Mouse myoblasts expressing a reporter gene alone (empty vector), VEGF, PDGF-BB or VEGF and PDGF-BB through a single bi-cistronic vector (VIP) were implanted into the temporalis muscle of an EMS following permanent ipsilateral internal carotid artery occlusion in adult, male C57BL\/6N mice. Over 84 days, myoblast engraftment and gene product expression, hemodynamic impairment, transpial collateralization, angiogenesis, pericyte recruitment and post-ischemic neuroprotection were assessed. By day 42, animals that received PDGF-BB in combination with VEGF (VIP) showed superior hemodynamic recovery, EMS collateralization and ischemic protection with improved pericyte recruitment around the parenchymal vessels and EMS collaterals. Also, supplementation of PDGF-BB resulted in a striking astrocytic activation with intrinsic VEGF mobilization in the cortex below the EMS. Our findings suggest that EMS surgery together with myoblast-mediated co-delivery of VEGF\/PDGF-BB may have the potential to serve as a novel treatment strategy for augmentation of collateral flow in the chronically hypoperfused brain.<\/jats:p>","DOI":"10.1177\/0271678x18818298","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T14:56:24Z","timestamp":1547045784000},"page":"404-419","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":56,"title":["Balanced single-vector co-delivery of VEGF\/PDGF-BB improves functional collateralization in chronic cerebral ischemia"],"prefix":"10.1177","volume":"40","author":[{"given":"Aiki","family":"Marushima","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Center for Stroke research Berlin (CSB), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Nieminen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Center for Stroke research Berlin (CSB), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kremenetskaia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Center for Stroke research Berlin (CSB), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gianni-Barrera","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Woitzik","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Center for Stroke research Berlin (CSB), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"von Degenfeld","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, Bayer Pharma AG, Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5737-8811","authenticated-orcid":false,"given":"Andrea","family":"Banfi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vajkoczy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Center for Stroke research Berlin (CSB), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Hecht","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Center for Stroke research Berlin (CSB), Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,1,9]]},"reference":[{"key":"bibr1-0271678X18818298","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1610"},{"key":"bibr2-0271678X18818298","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.12.1055"},{"key":"bibr3-0271678X18818298","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e3182621488"},{"key":"bibr4-0271678X18818298","first-page":"235","volume":"10","author":"Kredel FE","year":"1942","journal-title":"Southern 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