{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:10Z","timestamp":1787018110162,"version":"build-2736575974"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,2,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Ischemic stroke is among the most prevalent diseases, with high death and morbidity. Numerous preclinical studies have reported efficacious interventions in rodent stroke models. However, reperfusion therapies remain the only clinically efficacious intervention to date. Rigor and reproducibility are now recognized as critical to bridge the preclinical\u2013clinical disconnect. Inter\u2010\u03b1 inhibitor proteins (I\u03b1IPs) are a family of structurally related glycoproteins with 2 major forms (inter\u2010\u03b1 inhibitor and pre\u2010\u03b1 inhibitor) in blood. Purified human plasma\u2013derived I\u03b1IP has beneficial effects in sepsis and hypoxic\u2013ischemic brain injury. More recently, I\u03b1IP improved focal ischemic stroke outcomes in mouse models. Here, we tested I\u03b1IP efficacy in both transient and permanent stroke mouse models, mimicking previously published study designs and protocols to seek reproducibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Using healthy young male and female C57BL\/6 mice, we induced transient or permanent endovascular filament middle cerebral artery occlusion (MCAO). Mice were divided into transient MCAO+vehicle, transient MCAO+I\u03b1IP (30\u2009mg\/kg), permanent MCAO+vehicle, and permanent MCAO+I\u03b1IP groups. I\u03b1IP or vehicle was administered intravenously at 6 and 18\u2009hours after MCAO. End points were assessed at 2\u2009days. Efficacy readouts included death, infarct volume and swelling, and 3 neurological tests. Contrary to the previous work, we did not find I\u03b1IP efficacious on any outcome readout in either transient MCAO or permanent MCAO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our data highlight the contribution of interlaboratory heterogeneity to study outcomes and suggest that interventions considered for clinical development should undergo rigorous testing in multiple single\u2010laboratory studies before entering a multicenter preclinical trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.036034","type":"journal-article","created":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T05:31:51Z","timestamp":1738992711000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Examination of Inter\u2010\u03b1 Inhibitor Proteins in Permanent and Transient Focal Ischemia"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4422-2946","authenticated-orcid":false,"given":"Takahiko","family":"Imai","sequence":"first","affiliation":[{"name":"Neurovascular Research Unit, Department of Radiology Massachusetts General Hospital, Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-2552","authenticated-orcid":false,"given":"Andreia Lopes","family":"de Morais","sequence":"additional","affiliation":[{"name":"Neurovascular Research Unit, Department of Radiology Massachusetts General Hospital, Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Qin","sequence":"additional","affiliation":[{"name":"Neurovascular Research Unit, Department of Radiology Massachusetts General Hospital, Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Neurovascular Research Unit, Department of Radiology Massachusetts General Hospital, Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-7963","authenticated-orcid":false,"given":"Yow\u2010Pin","family":"Lim","sequence":"additional","affiliation":[{"name":"ProThera Biologics Inc. Providence RI USA"},{"name":"Department of Pathology and Laboratory Medicine The Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3644-6042","authenticated-orcid":false,"given":"Cenk","family":"Ayata","sequence":"additional","affiliation":[{"name":"Neurovascular Research Unit, Department of Radiology Massachusetts General Hospital, Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00252-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000211"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.032241"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2520339.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R300039200"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2920485"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/377642"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181e9fdf0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19859465"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114563"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2017.10.008"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612826666200421123242"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21239193"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01217-8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.07.012"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113442"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2024.e00341"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.01.016"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22451"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI144898"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003693"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.06.009"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adg8656"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2348-z"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148503"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.3791\/4038"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.040638"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hest.2020.09.001"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24565"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.036034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:24:03Z","timestamp":1739942643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.036034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,18]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,2,18]]}},"alternative-id":["10.1161\/JAHA.124.036034"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.036034","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,18]]},"assertion":[{"value":"2024-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e036034"}}