{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:38:50Z","timestamp":1790361530662,"version":"4.1.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:p>\n                    With increasing evidence for the existence of a cerebral thrombin system, coagulation factor IIa (thrombin) is suspected to influence the pathogenesis of secondary injury progression after intracerebral hemorrhage (ICH). We hypothesized that mechanisms associated with local volume expansion after ICH, rather than blood constituents, activate the cerebral thrombin system and are responsible for detrimental neurological outcome. To test this hypothesis, we examine the local thrombin expression after ICH in a C57BL\/6N mouse model in the presence and absence of blood constituents. ICH was established using stereotaxic orthotopic injection of utologous blood (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200910) or silicone oil as inert volume substance (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200910) into the striatum. Intracranial pressure (ICP), cerebral blood flow (CBF), and mean arterial blood pressure (MAP) were monitored during and 30\u2009min after the procedure. No significant differences between ICP, CBF, and MAP were found between both groups. Prothrombin messenger RNA expression was upregulated early after ICH. Immunohistochemistry showed an increase of perilesional thrombin in both groups (blood, 4.24-fold; silicone, 3.10-fold), whereas prothrombin fragment (F1.2) was elevated only in the absence of whole blood. Thrombin expression is colocalized with neuronal antigen expression. After 24\u2009h, lesion size and neuronal loss were similar. Perihematomal thrombin correlated with increased neuronal loss and detrimental neurological outcome\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . In our study, we demonstrate, for the first time, that the local cerebral thrombin system is activated after ICH and that this activation is independent of the presence of whole-blood constituents. In our study, neuronal damage is driven by local thrombin expression and leads to an adverse clinical outcome.\n                  <\/jats:p>","DOI":"10.1089\/neu.2019.6582","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T04:15:12Z","timestamp":1576210512000},"page":"1481-1490","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["The Cerebral Thrombin System Is Activated after Intracerebral Hemorrhage and Contributes to Secondary Lesion Growth and Poor Neurological Outcome in C57Bl\/6 Mice"],"prefix":"10.1177","volume":"37","author":[{"given":"Harald","family":"Krenzlin","sequence":"first","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."},{"name":"Department of Neurosurgery, and Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Gresser","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jussen","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."},{"name":"Department of Neurosurgery, HELIOS Dr. Horst-Schmidt-Kliniken, Wiesbaden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Riede","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Taylor","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Francisca","family":"Vogelaar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Ringel","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."},{"name":"Department of Neurosurgery, and Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Kempski","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Alessandri","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgical Pathophysiology, Johannes Gutenberg\u2013University Mainz, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60371-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01268.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3130353"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02331429"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00028.2003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0025"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01657-9"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90060-D"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-03-0131"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(91)90045-Y"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.119.4.1119"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000196133.74087.cb"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00183.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040552897"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-07-05389.1995"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.30.6.1247"},{"issue":"279","key":"e_1_3_3_18_2","first-page":"e123","article-title":"Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus","volume":"23","author":"Wu X.","year":"2011","unstructured":"Wu X., , Zhang W., , Li J.Y., , Chai B.X., , Peng J., , Wang H., , and Mulholland M.W. 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