{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T02:50:55Z","timestamp":1775184655283,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although endovascular mechanical thrombectomy demonstrates clinical efficacy in posterior circulation acute ischemic stroke (AIS), only one third of these patients attain functional independence with a third of patients\u2019 expiring despite vascular recanalization. Neuroprotection strategies, such as therapeutic hypothermia (TH) have been considered a promising adjunctive treatment in AIS. We propose the following rationale, design and protocol for a prospective randomized controlled trial (RCT) aimed to determine whether Vertebrobasilar Artery Cooling Infusion (VACI) improves functional outcomes in posterior circulation AIS patients post mechanical thrombectomy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Subjects in the study will be assigned randomly to either the cooling infusion or the control group in a 1:1 ratio (<jats:italic>n<\/jats:italic>\u2009=\u200940). Patients allocated to the cooling infusion group will receive 300\u2009ml cool saline at 4C through the catheter (30\u2009ml\/min) into vertebral artery after thrombectomy. The control group will receive the same volume of 37C saline. All patients enrolled will receive standard care according to current guidelines for stroke management. The primary outcome is symptomatic intracranial hemorrhage (ICH), whereas the secondary outcomes include functional outcome score, infarction volume, mortality, ICH, fatal ICH, cerebral vasospasm, coagulation abnormality, pneumonia and urinary infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussions<\/jats:title><jats:p>This study will determine the preliminary safety, feasibility, and neuroprotective benefits of VACI in posterior circulation AIS patients with reperfusion therapy. The results of this study may provide evidence for VACI as a new therapy in posterior circulation AIS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration:<\/jats:title><jats:p><jats:ext-link>www.chictr.org.cn<\/jats:ext-link>, ChiCTR2200065806, registered on November 15, 2022.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.1149767","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T06:01:37Z","timestamp":1681192897000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Vertebrobasilar artery cooling infusion in acute ischemic stroke for posterior circulation following thrombectomy: Rationale, design and protocol for a prospective randomized controlled trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhe","family":"Cheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchuan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary B.","family":"Rajah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenghai","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaokun","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"E4","DOI":"10.3171\/2017.1.FOCUS16514","article-title":"Neuroprotective delivery platforms as an adjunct to mechanical thrombectomy","volume":"42","author":"Babadjouni","year":"2017","journal-title":"Neurosurg. 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Neuroradiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1136\/svn-2017-000074","article-title":"The Chinese Stroke Association scientific statement: intravenous thrombolysis in acute ischaemic stroke","volume":"2","author":"Dong","year":"2017","journal-title":"Stroke Vasc Neurol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1161\/STROKEAHA.119.026523","article-title":"New endovascular approach for hypothermia with Intrajugular cooling and neuroprotective effect in ischemic stroke","volume":"51","author":"Duan","year":"2020","journal-title":"Stroke"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"c363","DOI":"10.1136\/bmj.c363","article-title":"Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data","volume":"340","author":"Edwards","year":"2010","journal-title":"BMJ"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1161\/hs1101.097382","article-title":"Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach","volume":"32","author":"Georgiadis","year":"2001","journal-title":"Stroke"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1016\/S0140-6736(16)00163-X","article-title":"Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials","volume":"387","author":"Goyal","year":"2016","journal-title":"Lancet"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1016\/S0140-6736(98)08020-9","article-title":"Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian acute stroke study Investigators","volume":"352","author":"Hacke","year":"1998","journal-title":"Lancet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1207092","DOI":"10.1155\/2021\/1207092","article-title":"Neuroprotective effects of early hypothermia induced by Phenothiazines and DHC in ischemic stroke","volume":"2021","author":"Han","year":"2021","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1161\/STROKEAHA.110.592295","article-title":"Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results","volume":"41","author":"Hemmen","year":"2010","journal-title":"Stroke"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/nur.20247","article-title":"Considerations in determining sample size for pilot studies","volume":"31","author":"Hertzog","year":"2008","journal-title":"Res. Nurs. 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Physiol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1161\/str.33.3.877","article-title":"Re: feasibility and safety of moderate hypothermia after massive hemispheric infarction","volume":"33","author":"Leker","year":"2002","journal-title":"Stroke"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4103\/bc.bc_27_22","article-title":"Perspectives on benefit of early and prereperfusion hypothermia by pharmacological approach in stroke","volume":"8","author":"Li","year":"2022","journal-title":"Brain Circ"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2888","DOI":"10.1161\/STROKEAHA.116.014200","article-title":"Results of the ICTuS 2 trial (intravascular cooling in the treatment of stroke 2)","volume":"47","author":"Lyden","year":"2016","journal-title":"Stroke"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"241","DOI":"10.4103\/bc.bc_59_21","article-title":"Protection of multiple ischemic organs by controlled reperfusion","volume":"7","author":"Ma","year":"2021","journal-title":"Brain Circ"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1136\/neurintsurg-2011-010150","article-title":"Brain temperature changes during selective cooling with endovascular intracarotid cold saline infusion: simulation using human data fitted with an integrated mathematical model","volume":"5","author":"Neimark","year":"2013","journal-title":"J Neurointerv Surg"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1056\/NEJMoa1310519","article-title":"Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest","volume":"369","author":"Nielsen","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa1706442","article-title":"Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct","volume":"378","author":"Nogueira","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"72","DOI":"10.14336\/AD.2020.0406","article-title":"Brain-derived CCR5 contributes to neuroprotection and brain repair after experimental stroke","volume":"12","author":"Ping","year":"2021","journal-title":"Aging Dis."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1080\/01616412.2020.1782122","article-title":"Ligustilide provides neuroprotection by promoting angiogenesis after cerebral ischemia","volume":"42","author":"Ren","year":"2020","journal-title":"Neurol. 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