{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:43:58Z","timestamp":1792669438661,"version":"4.5.0"},"reference-count":36,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>Tamoxifen has been shown to be a potent neuroprotectant against stroke in rodents. Because other neuroprotectant medications have failed in human trials, a study of tamoxifen in a large-animal model was necessary to further assess the drug's effectiveness. For this study, the authors developed an endovascular model of anterior circulation infarction in canines to mimic the human clinical condition. They assessed the following hypotheses: 1) that they will be able to consistently produce an internal carotid artery (ICA) terminus infarction and 2) that tamoxifen is an effective neuroprotectant against stroke in canines.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>In 24 male beagles (weight 9\u201311 kg), bilateral femoral artery cutdowns were performed, and the vertebral artery and left ICA were each selectively catheterized. Under fluoroscopic guidance, a microcatheter was introduced via the vertebral artery, guiding the catheter into the basilar artery, posterior communicating artery, and ICA terminus. A 1-ml clot was injected in the terminus, occluding the middle cerebral artery (MCA) and anterior cerebral artery (ACA) origin. In the first 12 canines, the occlusions were confirmed by angiography. A Canine Stroke Score (CSS) was assigned (score range 0\u201318 [0 = intact on examination, 18 = comatose]). The animals were then killed and their brains stained with 2,3,5-triphenyltetrazolium chloride (TTC). The subsequent 12 canines underwent a blinded randomized study in which the authors compared the results of tamoxifen (5 mg\/kg) infused intravenously 1 hour after clot injection with an equal volume of vehicle (dimethylsulfoxide). After 3 hours, the animals underwent MR imaging, were extubated, and clinical examinations were performed. The canines were killed at 8 hours after clot injection, and TTC staining was used.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In the first group, infarct volume and CSSs were consistent with the extent of the occlusion of the angiographic vessels. An occlusion of the ACA, MCA, and posterior cerebral artery resulted in larger infarcts and higher stroke scores than occlusion of the ACA and MCA. In the second group, tamoxifen significantly reduced infarct size and improved clinical outcomes. In tamoxifen-treated animals, the mean infarct volume reduction was 40% (p &lt; 0.05) and the mean CSS was significantly less than vehicle-treated animals (p &lt; 0.001). There were significant correlations among MR imaging-determined volume, TTC-determined volume, and neurological clinical outcome (p &lt; 0.05).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Using this endovascular model of stroke, the authors were able to consistently produce an infarction in the canines that was similar in scope to a carotid terminus occlusion in humans. Also, angiography could predict subsequent clinical course and infarct size. Tamoxifen was effective at significantly improving the canine neurological deficits and reducing the size of the stroke. This study took the first step in demonstrating the effectiveness of a promising human neuroprotectant in a large animal.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2010.8.jns09352","type":"journal-article","created":{"date-parts":[[2010,10,1]],"date-time":"2010-10-01T13:32:52Z","timestamp":1285939972000},"page":"1117-1126","source":"Crossref","is-referenced-by-count":27,"title":["Tamoxifen as an effective neuroprotectant in an endovascular canine model of stroke"],"prefix":"10.3171","volume":"114","author":[{"given":"Alan S.","family":"Boulos","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Deshaies","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Dalfino","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Feustel","sequence":"additional","affiliation":[{"name":"Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. John","family":"Popp","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doniel","family":"Drazin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns09352","series-title":"Stroke","first-page":"1655","article-title":"Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association\/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups","volume":"38","author":"Adams","year":"2007"},{"key":"b2-jns09352","series-title":"Neurology","first-page":"1595","article-title":"Diffusion-weighted MRI as an evolving standard of care in acute stroke","volume":"55","author":"Bakshi","year":"2000"},{"key":"b3-jns09352","series-title":"Cancer Res","first-page":"4328","article-title":"A permanently charged tamoxifen derivative displays anticancer activity and improved tissue selectivity in rodents","volume":"56","author":"Biegon","year":"1996"},{"key":"b4-jns09352","series-title":"J Pharm Sci","first-page":"644","article-title":"Pharmacokinetics of tamoxifen after intravenous and oral dosing of tamoxifen-hydroxybutenyl-betacyclodextrin formulations","volume":"96","author":"Buchanan","year":"2007"},{"key":"b5-jns09352","series-title":"Neurology","first-page":"1230","article-title":"Risk of ischemic stroke with tamoxifen treatment for breast cancer: a meta-analysis","volume":"63","author":"Bushnell","year":"2004"},{"key":"b6-jns09352","series-title":"Psychol Bull","first-page":"213","article-title":"Weighted kappa: nominal scale agreement with provision for scaled disagreement or partial credit","volume":"70","author":"Cohen","year":"1968"},{"key":"b7-jns09352","series-title":"Eur J Pharmacol","first-page":"65","article-title":"Treatment with tamoxifen reduces hypoxic-ischemic brain injury in neonatal rats","volume":"484","author":"Feng","year":"2004"},{"key":"b8-jns09352","series-title":"Stroke","first-page":"1164","article-title":"Volume-regulated anion channels are the predominant contributors to release of excitatory amino acids in the ischemic cortical penumbra","volume":"35","author":"Feustel","year":"2004"},{"key":"b9-jns09352","series-title":"Stroke","first-page":"1539","article-title":"Recommendations for advancing development of acute stroke therapies: Stroke Therapy Academic Industry Roundtable 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NXY-059","volume":"100","author":"Green","year":"2003"},{"key":"b14-jns09352","series-title":"Neurosurgery","first-page":"49","article-title":"Modification of a model for cerebral ischemia in the cat: a new method to occlude the middle cerebral artery","volume":"25","author":"Guo","year":"1989"},{"key":"b15-jns09352","series-title":"Neurosurgery","first-page":"986","article-title":"A canine model of acute hindbrain ischemia and reperfusion","volume":"36","author":"Guo","year":"1995"},{"issue":"2 Suppl","key":"b16-jns09352","series-title":"J Neurosurg","first-page":"123","article-title":"A new model of focal cerebral ischemia in the miniature pig","volume":"104","author":"Imai","year":"2006"},{"key":"b17-jns09352","series-title":"Recent Patents CNS Drug Discov","first-page":"104","article-title":"Tamoxifen as a powerful neuroprotectant in experimental stroke and implications for human stroke 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Homologous blood clot emboli in rats","volume":"13","author":"Kudo","year":"1982"},{"key":"b22-jns09352","series-title":"Pharmacol Rev","first-page":"151","article-title":"Basic guide to the mechanisms of antiestrogen action","volume":"50","author":"MacGregor","year":"1998"},{"key":"b23-jns09352","series-title":"Neuroendocrinology","first-page":"44","article-title":"Tamoxifen, a selective estrogen receptor modulator, reduces ischemic damage caused by middle cerebral artery occlusion in the ovariectomized female rat","volume":"77","author":"Mehta","year":"2003"},{"key":"b24-jns09352","series-title":"Neurosci Lett","first-page":"87","article-title":"Protective effect of tamoxifen on 1-methyl-4-phenylpyridine-induced hydroxyl radical generation in the rat striatum","volume":"308","author":"Obata","year":"2001"},{"key":"b25-jns09352","series-title":"J Neurochem","first-page":"1842","article-title":"Tamoxifen inhibits nitrotyrosine formation after reversible middle cerebral artery occlusion in the rat","volume":"76","author":"Osuka","year":"2001"},{"key":"b26-jns09352","series-title":"Clin Cancer Res","first-page":"1109","article-title":"A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood","volume":"3","author":"Pollack","year":"1997"},{"key":"b27-jns09352","series-title":"Stroke","first-page":"1368","article-title":"Reversible middle cerebral artery embolization in dogs without intracranial surgery","volume":"20","author":"Purdy","year":"1989"},{"key":"b28-jns09352","series-title":"Acta Radiol","first-page":"368","article-title":"Catheter replacement of the needle in percutaneous arteriography; a new technique","volume":"39","author":"Seldinger","year":"1953"},{"key":"b29-jns09352","series-title":"Stroke","first-page":"185","article-title":"Acute NMR changes during MCA occlusion: a preliminary study in primates","volume":"14","author":"Spetzler","year":"1983"},{"key":"b30-jns09352","series-title":"Stroke","first-page":"2752","article-title":"Recommendations for standards regarding preclinical neuroprotective and restorative drug development","volume":"30","author":"Stroke Therapy Academic Industry Roundtable (STAIR)","year":"1999"},{"key":"b31-jns09352","series-title":"N Engl J Med","first-page":"1581","article-title":"Tissue plasminogen activator for acute ischemic stroke","volume":"333","author":"The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group","year":"1995"},{"key":"b32-jns09352","series-title":"J Trauma","first-page":"1051","article-title":"Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery","volume":"31","author":"Tisherman","year":"1991"},{"key":"b33-jns09352","series-title":"Endocrinology","first-page":"367","article-title":"Tamoxifen neuroprotection in cerebral ischemia involves attenuation of kinase activation and superoxide production and potentiation of mitochondrial superoxide dismutase","volume":"149","author":"Wakade","year":"2008"},{"key":"b34-jns09352","series-title":"Exp Neurol","first-page":"41","article-title":"Behavioral and histological neuroprotection by tamoxifen after reversible focal cerebral ischemia","volume":"196","author":"Zhang","year":"2005"},{"key":"b35-jns09352","series-title":"Exp Neurol","first-page":"819","article-title":"Neuroprotection by tamoxifen in focal cerebral ischemia is not mediated by an agonist action at estrogen receptors but is associated with antioxidant activity","volume":"204","author":"Zhang","year":"2007"},{"key":"b36-jns09352","series-title":"Science","first-page":"1289","article-title":"Tissue plasminogen activator reduces neurological damage after cerebral embolism","volume":"230","author":"Zivin","year":"1985"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/114\/4\/article-p1117.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/114\/4\/article-p1117.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/114\/4\/article-p1117.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:34:09Z","timestamp":1679895249000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/114\/4\/article-p1117.xml"}},"subtitle":["Laboratory investigation"],"short-title":[],"issued":{"date-parts":[[2011,4]]},"references-count":36,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3171\/2010.8.jns09352","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4]]}}}