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Bradykinin (BK) is a mediator of vasogenic edema. It could contribute to the pathogenesis of central nervous system malaria in Kenyan children and\n                  <jats:italic>P. berghei<\/jats:italic>\n                  ANKA (\n                  <jats:italic>PbA<\/jats:italic>\n                  ) infected C57BL\/6J mice with experimental cerebral malaria. Cleaved plasma high molecular weight kininogen (cHK) is a marker for prior BK release. 40% of children with central nervous system malaria had plasma cHK versus 18% of children with uncomplicated malaria. Wild-type\n                  <jats:italic>PbA<\/jats:italic>\n                  -infected mice had circulating plasma cHK, elevated BK levels, and reduced HK and prekallikrein levels. HK null (\n                  <jats:italic>\n                    Kng1\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ), combined BK B1 and B2 receptor null (\n                  <jats:italic>\n                    Bdkrb1\n                    <jats:sup>-\/-<\/jats:sup>\n                    \/ Bdkrb2\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ), BK B2 (\n                  <jats:italic>\n                    Bdkrb2\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ) or BK B1 (\n                  <jats:italic>\n                    Bdkrb1\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ) receptor null mice were protected from neurologic deterioration and brain edema compared to wild-type mice.\n                  <jats:italic>\n                    F12\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice were not protected from neurological deterioration.\n                <\/jats:p>\n                <jats:p>\n                  Prekallikrein null (\n                  <jats:italic>\n                    Klkb1\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ), prolylcarboxypeptidase hypomorphs (\n                  <jats:italic>\n                    Prcp\n                    <jats:sup>gt\/gt<\/jats:sup>\n                  <\/jats:italic>\n                  ), and brain endothelial cell conditional knockout of PRCP (\n                  <jats:italic>\n                    Prcp\n                    <jats:sup>fl\/fl<\/jats:sup>\n                  <\/jats:italic>\n                  Cre) mice had reduced neurologic deterioration and brain edema. Adjuvant plasma kallikrein inhibition combined with artesunate treatment of\n                  <jats:italic>PbA<\/jats:italic>\n                  -infected mice reversed neurologic deterioration and brain edema and prolonged survival relative to artesunate alone. BK-induced vasogenic edema contributes to human and murine CM.\n                <\/jats:p>","DOI":"10.64898\/2026.02.23.704410","type":"posted-content","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T17:40:13Z","timestamp":1772127613000},"source":"Crossref","is-referenced-by-count":0,"title":["Bradykinin Contributes to Vasogenic Edema in Murine Experimental Cerebral Malaria"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2384-8733","authenticated-orcid":false,"given":"Alessandro de Sa","family":"Pinheiro","sequence":"first","affiliation":[{"name":"Case Western Reserve University, Cleveland OH, 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas E.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1975-8033","authenticated-orcid":false,"given":"Rodrigo P.","family":"Silva-Aguiar","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland OH, 44106, USA"},{"name":"Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Jun","family":"Shim","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland OH, 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alona A.","family":"Merkulova","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland OH, 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-2828","authenticated-orcid":false,"given":"Sadiq","family":"Silbak","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland OH, 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yelenna","family":"Skomorovska-Prokvolit","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland OH, 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Midem","sequence":"additional","affiliation":[{"name":"Chulaimbo Sub-County Hospital, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-6164","authenticated-orcid":false,"given":"Sidney","family":"Ogolla","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Kisumu, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1782-9937","authenticated-orcid":false,"given":"Bjoern B.","family":"Burckhardt","sequence":"additional","affiliation":[{"name":"Pharmacotherapy, Institute of Pharmaceutical and Medicinal Chemistry, University of Muenster, Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7573-6631","authenticated-orcid":false,"given":"Tanja","family":"Gangnus","sequence":"additional","affiliation":[{"name":"Pharmacotherapy, Institute of Pharmaceutical and Medicinal Chemistry, University of Muenster, Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7510-7625","authenticated-orcid":false,"given":"Julio","family":"Scharfstein","sequence":"additional","affiliation":[{"name":"Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-7753","authenticated-orcid":false,"given":"Celso","family":"Caruso-Neves","sequence":"additional","affiliation":[{"name":"Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-0124","authenticated-orcid":false,"given":"Owen J.T.","family":"McCarty","sequence":"additional","affiliation":[{"name":"Oregon Health & Science University, Portland OR, 97239; 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