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Since bradykinin (BK) is a mediator of vasogenic edema, we hypothesized that it contributes to the pathogenesis of CM in Kenyan children and\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    <jats:italic>berghei<\/jats:italic>\n                    ANKA\u2013infected (\n                    <jats:italic>PbA<\/jats:italic>\n                    -infected) C57BL\/6J mice in experimental CM (ECM). Cleaved plasma high-molecular-weight kininogen (cHK) is a marker for 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 with ECM had circulating cHK, elevated BK levels, and reduced HK and prekallikrein activity\/antigen levels. HK-null (\n                    <jats:italic>\n                      Kng1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ), combined BK B1\u2013 and B2 receptor\u2013null (\n                    <jats:italic>\n                      Bdkrb1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      Bdkrb2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ), BK B2 receptor\u2013null (\n                    <jats:italic>\n                      Bdkrb2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ), or BK B1 receptor\u2013null (\n                    <jats:italic>\n                      Bdkrb1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice were protected significantly from neurologic deterioration and brain edema compared with wild-type mice.\n                    <jats:italic>\n                      F12\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice were not protected from neurological deterioration. Prekallikrein-null (\n                    <jats:italic>\n                      Klkb1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ), prolylcarboxypeptidase hypomorph (\n                    <jats:italic>\n                      Prcp\n                      <jats:sup>gt\/gt<\/jats:sup>\n                    <\/jats:italic>\n                    ), and brain endothelial cell conditional KO of PRCP (\n                    <jats:italic>\n                      Prcp\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    Cre) mice with ECM had reduced neurologic deterioration and brain edema. Adjuvant plasma kallikrein inhibition combined with artesunate treatment in\n                    <jats:italic>PbA<\/jats:italic>\n                    -infected mice reversed neurologic deterioration and brain edema and significantly prolonged survival over artesunate alone. BK-induced vasogenic edema contributes to human and murine CM.\n                  <\/jats:p>","DOI":"10.1172\/jci202285","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:01:25Z","timestamp":1784044885000},"source":"Crossref","is-referenced-by-count":0,"title":["Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria"],"prefix":"10.1172","volume":"136","author":[{"given":"Alessandro","family":"de Sa Pinheiro","sequence":"first","affiliation":[{"name":"Case Western Reserve University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo P.","family":"Silva-Aguiar","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, Ohio, 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