{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:01:04Z","timestamp":1789624864782,"version":"build-2803163510"},"reference-count":72,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">In spite of the advances in understanding the pathophysiology of stroke, successful treatment remains a major challenge. The lack of consideration of preclinical studies with associated comorbidities is a primary factor for the translational failure, as ~94% of patients with stroke have \u22651 preexisting comorbidities. Because hypertension is the most common comorbid condition in patients with stroke and predisposition to hypertension is known to worsen stroke outcome, we evaluated the efficacy of a novel neuroprotective peptide derived from the brain\u2010enriched and neuron\u2010specific tyrosine phosphatase striatal enriched phosphatase (STEP) in attenuating ischemic brain damage under hypertensive conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Mild ischemic insult was induced in hypertensive rats by middle cerebral artery occlusion for 60\u2009minutes followed by reperfusion for 30\u2009days. In a subset of hypertensive rats, the STEP\u2010mimetic peptide (STEP\u2010peptide) was administered intravenously 6\u2009hours after the onset of the insult. Magnetic resonance imaging scans of the brain were done 1, 7, and 28\u2009days after the insult to assess temporal evolution of ischemic brain damage. Behavioral studies were performed weekly starting 7\u2009days after the onset of the insult. Histopathological staining of brain sections was done 30\u2009days later.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">The results show that delayed treatment with a single intravenous administration of the STEP\u2010peptide 6\u2009hours after the onset of the insult reduces mortality rate. In the surviving rats, T2\u2010weighted imaging, and diffusion tensor imaging of the brain on post\u2010stroke days 1, 7, and 28 show significant reduction in infarct size and improvement of structural integrity within the infarcted area following treatment. Furthermore, behavioral studies show significant improvement in motor coordination, sensory motor function, and spatial memory over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">The efficacy of the novel STEP\u2010peptide in mitigating brain damage and improving functional recovery in a preclinical stroke model of hypertension holds promise for the development of potential strategies to treat acute ischemic stroke in the population with hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.042669","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:46:48Z","timestamp":1768391208000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Regulating the Impact of Hypertension on Stroke: Therapeutic Potential of 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