{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:10:47Z","timestamp":1783671047029,"version":"3.55.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The Stroke Preclinical Assessment Network tested 6 therapeutic interventions initiated at the time of reperfusion after focal ischemic stroke in young mice, aging mice, obese mice, and spontaneously hypertensive rats. This randomized, controlled trial was conducted across 6 sites with concealed treatment and blinded neurobehavior assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages. The primary outcome was turning preference on the corner test at 1\u2009month. The PARP (poly(ADP\u2010ribose) polymerase) inhibitor, veliparib, was considered futile after the second stage when pooling all animal models (\n              <jats:italic toggle=\"no\">n<\/jats:italic>\n              =231 veliparib;\n              <jats:italic toggle=\"no\">n<\/jats:italic>\n              =344 placebo).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">A secondary analysis was performed to evaluate veliparib treatment on primary and secondary outcomes in individual subgroup models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Intravenous injection of veliparib at reperfusion failed to show a benefit on the corner test at 7 or 30\u2009days of recovery in young mice, obese mice, or spontaneously hypertensive rats. However, in aging mice (15\u201318 months old), veliparib significantly improved performance on the corner test at 7 (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.007) and 30 (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.03) days and reduced foot\u2010faults on the grid walk test at 7 (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.024) and 30 (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.008) days. These effects were independent of sex. Treatment had no effect on magnetic resonance imaging\u2010determined lesion volume. The survival was similar with placebo and veliparib treatments across subgroups, although mortality was high in aging mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Veliparib improved functional outcome in aging mice. Because ischemic stroke predominantly occurs in the aging population, further research into the benefit of PARP inhibitors in aged animal models of stroke is warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.040914","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:08:56Z","timestamp":1758802136000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Multicenter Stroke Preclinical Assessment Network Analysis of Cardiovascular Risk Factor Subgroups Treated With the Poly(ADP\u2010Ribose) Polymerase Inhibitor Veliparib"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-9992","authenticated-orcid":false,"given":"Raymond C.","family":"Koehler","sequence":"first","affiliation":[{"name":"Johns Hopkins University","place":["Baltimore, 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