{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:30:29Z","timestamp":1793345429744,"version":"4.5.0"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study examined the dose\u2010dependent efficacy and pharmacokinetics of R18D in a rat transient middle cerebral artery occlusion (MCAO) stroke model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>R18D was intravenously administered 60\u2009min after the onset of a 90\u2010min MCAO induced by intraluminal filament insertion. For pharmacokinetic profiling, blood samples were collected 10, 15, 30 and 60\u2009min, and at 2, 4 and 8\u2009h after the start of a 10\u2010min intravenous infusion of R18D. Infarct volume and body weight were assessed at 24\u2009h after MCAO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">R18D<\/jats:styled-content>\n                      reduced mean total infarct volume by 47.2% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003), 28.4% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008), and 27.9% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003) at doses of 325, 650 and 1100\u2009nmol\/kg, respectively. The 650\u2009nmol\/kg dose significantly reduced cerebral hemisphere swelling by 8.3% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), whereas the 325\u2009nmol\/kg (5.6%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.15) and 1100\u2009nmol\/kg (4.5%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.14) doses produced non\u2010significant reductions in swelling.\n                      <jats:styled-content style=\"fixed-case\">R18D<\/jats:styled-content>\n                      did not significantly affect post\u2010stroke weight loss, however rats treated with the lowest dose (325\u2009nmol\/kg) exhibited the smallest reduction in body weight compared with vehicle\u2010treated animals (7.35% vs. 9.35). Pharmacokinetic analysis of the three\n                      <jats:styled-content style=\"fixed-case\">R18D<\/jats:styled-content>\n                      doses after stroke demonstrated a half\u2010life of 72 to 78\u2009min, with dose\u2010dependent plasma Cmax values of 5.3\u2009\u03bcg\/\n                      <jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>\n                      , 11.9\u2009\u03bcg\/mL and 17.3\u2009\u03bcg\/mL for the low\u2010, medium\u2010 and high\u2010dose groups, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results further support the neuroprotective properties of R18D and provide strong justification for its continued development as a neuroprotective treatment for ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70969","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:49:22Z","timestamp":1780498162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Neuroprotective Efficacy of Poly\u2010Arginine Peptide\n                    <scp>R18D<\/scp>\n                    in Sprague Dawley Rats Subjected to Transient Intraluminal Filament Middle Cerebral Artery Occlusion Stroke"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0964-0648","authenticated-orcid":false,"given":"Bruno P.","family":"Meloni","sequence":"first","affiliation":[{"name":"Perron Institute for Neurological and Translational Science  Nedlands Western Australia Australia"},{"name":"Department of Neurosurgery Sir Charles Gairdner Hospital, QEII Medical Centre  Nedlands Western Australia Australia"},{"name":"Centre for Neuromuscular and Neurological Disorders, the University of Western Australia  Nedlands Western Australia Australia"},{"name":"Argenica Therapeutics  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart K.","family":"Gribble","sequence":"additional","affiliation":[{"name":"Argenica Therapeutics  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan G.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Argenica Therapeutics  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayelet","family":"Weksler","sequence":"additional","affiliation":[{"name":"MD Biosciences Innovalora, Ltd.  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