{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T16:57:03Z","timestamp":1759683423530},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,10,21]],"date-time":"2015-10-21T00:00:00Z","timestamp":1445385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Institution Funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>Thrombin, a key player in thrombogenesis, affects cells in the brain through activation of its receptors. Low levels of thrombin activity are protective while high levels are toxic. We sought to quantify thrombin activity levels and their spatial distribution in brains of mice following reperfusion after ischemic stroke focusing on infarct, peri\u2010infarct and contralateral areas. In order to find out the contribution of brain\u2010derived thrombin, m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels of both prothrombin and factor X were determined. Furthermore, we assessed the effect of thrombin levels that were measured in the ischemic brain on synaptic transmission. We found that in the brains of mice following transient middle cerebral artery occlusion, thrombin activity is elevated throughout the ischemic hemisphere, including in peri\u2010infarct areas (90\u00a0\u00b1\u00a033 and 60\u00a0\u00b1\u00a018\u00a0mU\/mL, in the infarct and peri\u2010infarct areas, respectively, compared to 11\u00a0\u00b1\u00a03 and 12\u00a0\u00b1\u00a05\u00a0mU\/mL, in the corresponding contralateral areas; mean\u00a0\u00b1\u00a0SE; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Brain m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels of prothrombin and, in particular, factor X are up\u2010regulated in the ischemic core. Hippocampal slices treated with thrombin concentrations as found in the ischemic hemisphere show altered synaptic responses. We conclude that high thrombin activity following reperfusion after ischemic stroke may cause synaptic dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:label \/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13372-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nFollowing transient middle cerebral artery occlusion in mice, thrombin activity is elevated throughout the ischemic hemisphere, including in peri\u2010infarct areas. Brain mRNA levels of prothrombin and factor X are up\u2010regulated in the ischemic core. Thrombin is known to affect synaptic function in a concentration dependent manner and hippocampal slices treated with the concentrations found in the ischemic hemisphere show altered synaptic responses. We conclude that in ischemic stroke, the high brain thrombin activity found after reperfusion may cause synaptic dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13372","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T12:15:03Z","timestamp":1442924103000},"page":"1140-1148","source":"Crossref","is-referenced-by-count":25,"title":["Increased thrombin activity following reperfusion after ischemic stroke alters synaptic transmission in the hippocampus"],"prefix":"10.1111","volume":"135","author":[{"given":"Doron","family":"Bushi","sequence":"first","affiliation":[{"name":"Comprehensive Stroke Center Department of Neurology and The J. Sagol Neuroscience Center Chaim Sheba Medical Center Tel HaShomer Israel"},{"name":"Department of Physiology and Pharmacology Sackler Faculty of Medicine Tel Aviv University Tel\u00a0Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Ben Shimon","sequence":"additional","affiliation":[{"name":"Comprehensive Stroke Center Department of Neurology and The J. Sagol Neuroscience Center Chaim Sheba Medical Center Tel HaShomer Israel"},{"name":"Department of Physiology and Pharmacology Sackler Faculty of Medicine Tel Aviv University Tel\u00a0Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efrat","family":"Shavit Stein","sequence":"additional","affiliation":[{"name":"Comprehensive Stroke Center Department of Neurology and The J. 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