{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:44:19Z","timestamp":1777927459157,"version":"3.51.4"},"reference-count":79,"publisher":"SAGE Publications","issue":"21-22","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"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":[[2024,11]]},"abstract":"<jats:p>\n                    The kallikrein\u2013kinin system is one of the first inflammatory pathways to be activated following traumatic brain injury (TBI) and has been shown to exacerbate brain edema formation in the acute phase through activation of bradykinin 2 receptors (B2R). However, the influence of B2R on chronic post-traumatic damage and outcome is unclear. In the current study, we assessed long-term effects of B2R-knockout (KO) after experimental TBI. B2R KO mice (heterozygous, homozygous) and wild-type (WT) littermates (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 10\/group) were subjected to controlled cortical impact (CCI) TBI. Lesion size was evaluated by magnetic resonance imaging up to 90 days after CCI. Motor and memory function were regularly assessed by Neurological Severity Score, Beam Walk, and Barnes maze test. Ninety days after TBI, brains were harvested for immunohistochemical analysis. There was no difference in cortical lesion size between B2R-deficient and WT animals 3 months after injury; however, hippocampal damage was reduced in B2R KO mice (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.03). Protection of hippocampal tissue was accompanied by a significant improvement of learning and memory function 3 months after TBI (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.02 WT vs. KO), whereas motor function was not influenced. Scar formation and astrogliosis were unaffected, but B2R deficiency led to a gene-dose-dependent attenuation of microglial activation and a reduction of CD45+ cells 3 months after TBI in cortex (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.0003) and hippocampus (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.0001). These results suggest that chronic hippocampal neurodegeneration and subsequent cognitive impairment are mediated by prolonged neuroinflammation and B2R. Inhibition of B2R may therefore represent a novel strategy to reduce long-term neurocognitive deficits after TBI.\n                  <\/jats:p>","DOI":"10.1089\/neu.2024.0042","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T05:53:16Z","timestamp":1717134796000},"page":"2442-2454","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Bradykinin 2 Receptors Mediate Long-Term Neurocognitive Deficits After Experimental Traumatic Brain Injury"],"prefix":"10.1177","volume":"41","author":[{"given":"Antonia Clarissa","family":"Wehn","sequence":"first","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Munich, Germany."},{"name":"Munich Cluster for Systems Neurology (SyNergy), Munich, Germany."},{"name":"Department of Neurosurgery, LMU University Hospital, LMU Munich, Munich, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Khalin","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Munich, Germany."},{"name":"Munich Cluster for Systems Neurology (SyNergy), Munich, Germany."},{"name":"Institute Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Rouen, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senbin","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Munich, Germany."},{"name":"Munich Cluster for Systems Neurology (SyNergy), Munich, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biyan Nathanael","family":"Harapan","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Munich, Germany."},{"name":"Department of Neurosurgery, LMU University Hospital, LMU Munich, Munich, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Mao","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Munich, Germany."},{"name":"Munich Cluster for Systems Neurology (SyNergy), Munich, Germany."},{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China."},{"name":"Neurotrauma Laboratory, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Munich, Germany."},{"name":"Munich Cluster for Systems Neurology (SyNergy), Munich, Germany."},{"name":"Department of Neurosurgery, The Second affiliated Hospital of Nanchang 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