{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:39:20Z","timestamp":1778805560546,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T00:00:00Z","timestamp":1537574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS084921"],"award-info":[{"award-number":["R01 NS084921"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hemorrhagic transformation after ischemic stroke is an independent predictor for poor outcome and is characterized by blood vessel rupture leading to brain edema. To date, no therapies for preventing hemorrhagic transformation exist. Disintegrins from the venom of <jats:italic>Crotalus atrox<\/jats:italic> have targets within the coagulation cascade, including receptors on platelets. We hypothesized that disintegrins from <jats:italic>C. atrox<\/jats:italic> venom can attenuate hemorrhagic transformation by preventing activation of matrix metalloproteinase after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. We subjected 48 male Sprague\u2010Dawley rats weighing 240\u2013260\u00a0g to MCAO and hyperglycemia to induce hemorrhagic transformation of the infarction. At reperfusion, we administered either saline (vehicle), whole <jats:italic>C. atrox<\/jats:italic> venom (two doses were used), or fractionated <jats:italic>C. atrox<\/jats:italic> venom (HPLC Fraction 2). Rats were euthanized 24\u00a0hr post\u2010ictus for measurement of infarction and hemoglobin volume. Reversed\u2010phase HPLC was performed to fractionate the whole venom and peaks were combined to form Fraction 2, which contained the disintegrin Crotatroxin. Fraction 2 protected against hemorrhagic transformation after MCAO, and attenuated activation of matrix metalloproteinase\u20109. Administering matrix metalloproteinase antagonists prevented the protection by Fraction 2. The results of this study indicate that disintegrins found in <jats:italic>C. atrox<\/jats:italic> venom may have therapeutic potential for reducing hemorrhagic transformation after ischemic stroke. Moreover, the RP\u2010HPLC fractions retained sufficient protein activity to suggest that gentler and less efficient orthogonal chromatographic methods may be unnecessary to isolate proteins and explore their function.<\/jats:p>","DOI":"10.1002\/jnr.24334","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T13:15:26Z","timestamp":1537622126000},"page":"191-200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<i>Crotalus atrox<\/i> disintegrin reduces hemorrhagic transformation by attenuating matrix metalloproteinase\u20109 activity after middle cerebral artery occlusion in hyperglycemic male rats"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-3353","authenticated-orcid":false,"given":"Devin W.","family":"MBride","sequence":"first","affiliation":[{"name":"The Vivian L. Smith Department of Neurosurgery, McGovern Medical School The University of Texas Health Science Center at Houston Houston Texas"},{"name":"Department of Physiology &amp; Pharmacology Loma Linda University School of Medicine Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric C. K.","family":"Gren","sequence":"additional","affiliation":[{"name":"Department of Earth and Biological Sciences Loma Linda University School of Medicine Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne","family":"Kelln","sequence":"additional","affiliation":[{"name":"Department of Earth and Biological Sciences Loma Linda University School of Medicine Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William K.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Earth and Biological Sciences Loma Linda University School of Medicine Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology Loma Linda University School of Medicine Loma Linda California"},{"name":"Department of Neurosurgery Loma Linda University School of Medicine Loma Linda California"},{"name":"Department of Anesthesiology Loma Linda University School of Medicine Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,22]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"1","article-title":"Small vessel disease is associated with tissue inhibitor of matrix metalloproteinase\u20104 after ischaemic stroke","author":"Arba F.","year":"2018","journal-title":"Translational Stroke Research"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(81)90117-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000558"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000046764.57344.31"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-016-7610-9"},{"key":"e_1_2_12_7_1","first-page":"1","article-title":"Baicalin attenuates blood\u2013brain barrier disruption and hemorrhagic transformation and improves neurological outcome in ischemic stroke rats with delayed t\u2010PA treatment: Involvement of ONOO(\u2010)\u2010MMP\u20109 pathway","author":"Chen H.","year":"2017","journal-title":"Translational Stroke Research"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.11.2296"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-017-0586-7"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-011-0083-3"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199909000-00010"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2006.11.020"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115124"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-017-0526-6"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40821"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00032"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-66913-2"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1179\/1743132813Y.0000000209"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000115297.92132.84"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0459-5"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.021"},{"issue":"3","key":"e_1_2_12_22_1","first-page":"211","article-title":"Diagnostic uses of snake venom","volume":"31","author":"Marsh N. A.","year":"2001","journal-title":"Haemostasis"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-015-0400-3"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18497-5_42"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","unstructured":"Recommendations for standards regarding preclinical neuroprotective and restorative drug development. (1999).Stroke 30 2752\u20132758.https:\/\/doi.org\/10.1161\/01.str.30.12.2752","DOI":"10.1161\/01.STR.30.12.2752"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-014-0381-7"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90681-X"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-017-0552-4"},{"issue":"2","key":"e_1_2_12_29_1","first-page":"393","article-title":"Hypotensive and hemostatic properties of rattlesnake (Crotalus viridis helleri) venom and venom fractions in dogs","volume":"230","author":"Schaeffer R. C.","year":"1984","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0447-9"},{"key":"e_1_2_12_31_1","doi-asserted-by":"crossref","unstructured":"Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS): Bridging basic and clinical science for cellular and neurogenic factor therapy in treating stroke.(2009).Stroke 40(2) 510\u2013515.https:\/\/doi.org\/10.1161\/strokeaha.108.526863","DOI":"10.1161\/STROKEAHA.108.526863"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.03.036"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600375"},{"issue":"8","key":"e_1_2_12_34_1","first-page":"81","article-title":"Hemorrhagic transformation after cerebral infarction: Current concepts and challenges","volume":"2","author":"Zhang J.","year":"2014","journal-title":"Annals of Translational Medicine"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.24334","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.24334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T10:58:33Z","timestamp":1694170713000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.24334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,22]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/jnr.24334"],"URL":"https:\/\/doi.org\/10.1002\/jnr.24334","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,22]]},"assertion":[{"value":"2018-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}