{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:10:17Z","timestamp":1784765417778,"version":"3.55.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Direct extracranial\u2013intracranial bypass surgery for treatment of cerebral hemodynamic compromise remains hindered by complications but alternative simple and safe indirect revascularization procedures, such as an encephalomyosynangiosis (EMS), lack hemodynamic efficiency. Here, the myoblast-mediated transfer of angiogenic genes presents an approach for induction of therapeutic collateralization. In this study, we tested the effect of myoblast-mediated delivery of vascular endothelial growth factor-A (VEGF) to the muscle\/brain interface of an EMS in a model of chronic cerebral hypoperfusion.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              Permanent unilateral internal carotid artery-occlusion was performed in adult C57\/BL6 mice with or without (no EMS) surgical grafting of an EMS followed by implantation of monoclonal mouse myoblasts expressing either VEGF\n              <jats:sub>164<\/jats:sub>\n              or an empty vector (EV). Cerebral hemodynamic impairment, transpial collateralization, angiogenesis, mural cell investment, microvascular permeability, and cortical infarction after ipsilateral stroke were assessed by real-time laser speckle blood flow imaging, 2- and 3-dimensional immunofluorescence and MRI.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              VEGF-expressing myoblasts improved hemodynamic rescue by day 14 (no EMS 37\u00b121%, EV 42\u00b19%, VEGF 48\u00b112%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05 for VEGF versus no EMS and versus EV), together with the EMS take rate (VEGF 60%, EV 18.2%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) and angiogenesis of mature cortical microvessels below the EMS (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05 for VEGF versus EV). Importantly, functional and morphological results were paralleled by a 25% reduction of cortical infarction after experimental stroke on the side of the EMS.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Myoblast-mediated VEGF supplementation at the target site of an EMS could help overcome the clinical dilemma of poor surgical revascularization results and provide protection from ischemic stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.114.006712","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T03:58:58Z","timestamp":1415764738000},"page":"203-211","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Myoblast-Mediated Gene Therapy Improves Functional Collateralization in Chronic Cerebral Hypoperfusion"],"prefix":"10.1161","volume":"46","author":[{"given":"Nils","family":"Hecht","sequence":"first","affiliation":[{"name":"From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiki","family":"Marushima","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Nieminen","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kremenetskaia","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"von Degenfeld","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Woitzik","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vajkoczy","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Germany (N.H., A.M., M.N., I.K., J.W., P.V.); and Baxter Laboratory for Stem Cell Biology, Stanford University, CA (G.v.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1610"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3171\/2012.9.JNS12551"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.17pt1.29"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3171\/2008.6.PEDS0834"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3171\/2009.1.FOCUS08298"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3171\/2009.4.JNS081649"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804622"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21981"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3171\/2008.9.JNS17658"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000330351"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-008-0760-x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.112.279109"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.181115"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780013"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64062-X"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.8.898"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-441527"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18420"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6568fje"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.07.011"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)46054-5"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.125.6.1275"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02721371"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.112.653204"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00010-8"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.112.119321"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2005.103.5.0882"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.50.449"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9369"},{"issue":"1","key":"e_1_3_3_31_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/brain\/awh325","article-title":"VEGF overexpression induces post-ischaemic neuroprotection, but facilitates haemodynamic steal phenomena.","volume":"128","author":"Wang Y","year":"2005","unstructured":"Wang Y, Kilic E, Kilic U, Weber B, Bassetti CL, Marti HH, et al.. 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Brain. 2005;128(pt 1):52\u201363.","journal-title":"Brain"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.111.000240"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.12.1055"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf047"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.73.1.88"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07424"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.107.161521"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000095791.85737.65"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.114.006712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T17:49:56Z","timestamp":1717177796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.114.006712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1161\/STROKEAHA.114.006712"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.114.006712","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"2014-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}