{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:28:00Z","timestamp":1790666880335,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T00:00:00Z","timestamp":1386288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Activation of angiotensin\u2010converting enzyme 2, resulting in production of angiotensin\u2010(1\u20137) and stimulation of its receptor, Mas, exerts beneficial actions in a number cardiovascular diseases, including ischaemic stroke. A potential beneficial role for angiotensin\u2010(1\u20137) in haemorrhagic stroke has not previously been reported.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Central administration of angiotensin\u2010(1\u20137) into stroke\u2010prone spontaneously hypertensive rats, a model of haemorrhagic stroke, increases lifespan and improves the neurological status of these rats, as well as decreasing microglial numbers in the striatum (implying attenuation of cerebral inflammation). These actions of angiotensin\u2010(1\u20137) have not previously been reported and identify this peptide as a potential new therapeutic target in haemorrhagic stroke.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Angiotensin\u2010(1\u20137) [Ang\u2010(1\u20137)] exerts cerebroprotective effects in ischaemic stroke, and this action is associated with a blunting of intracerebral inflammatory processes and microglial activation. Given that intracerebral inflammation and microglial activation play key roles in the mechanism of injury and brain damage in both ischaemic and haemorrhagic stroke, we have investigated the potential beneficial actions of Ang\u2010(1\u20137) in stroke\u2010prone spontaneously hypertensive rats (spSHRs), an established animal model of hypertension\u2010induced haemorrhagic stroke. Angiotensin\u2010(1\u20137) was administered by continuous infusion via the intracerebroventricular route for 6 weeks into spSHRs fed a high\u2010sodium (4%) diet, starting at 49 days of age. This treatment resulted in a significant increase in survival of the spSHRs. Median survival was 108 days in control, artificial cerebrospinal fluid\u2010infused spSHRs and 154 days in Ang\u2010(1\u20137)\u2010treated spSHRs. This effect was partly reversed by intracerebroventricular infusion of the Mas receptor blocker, A779. This Ang\u2010(1\u20137) treatment also decreased the number of haemorrhages in the striatum, improved neurological status (reduced lethargy), decreased the number of microglia in the striatum and tended to increase neuron survival at the same site. Importantly, infusions of Ang\u2010(1\u20137) had no effect on kidney pathology, heart pathology, body weight, serum corticosterone levels or blood pressure. This study is the first to demonstrate the cerebroprotective actions of Ang\u2010(1\u20137), including increased survival time, in spSHRs. As such, these data reveal a potential therapeutic target for haemorrhagic stroke.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2013.075242","type":"journal-article","created":{"date-parts":[[2013,10,19]],"date-time":"2013-10-19T05:06:49Z","timestamp":1382159209000},"page":"442-453","source":"Crossref","is-referenced-by-count":57,"title":["Centrally administered angiotensin\u2010(1\u20137) increases the survival of stroke\u2010prone spontaneously hypertensive rats"],"prefix":"10.1113","volume":"99","author":[{"given":"Robert W.","family":"Regenhardt","sequence":"first","affiliation":[{"name":"Department of Physiology and Functional Genomics"},{"name":"McKnight Brain Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Mecca","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics"},{"name":"McKnight Brain Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Desland","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics"},{"name":"McKnight Brain Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip F.","family":"Ritucci\u2010Chinni","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics"},{"name":"McKnight Brain Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Ludin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics"},{"name":"McKnight Brain Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics"},{"name":"McKnight Brain Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Banuelos","sequence":"additional","affiliation":[{"name":"McKnight Brain Institute"},{"name":"Department of Neuroscience"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Bizon","sequence":"additional","affiliation":[{"name":"McKnight Brain Institute"},{"name":"Department of Neuroscience"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Reinhard","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Pathology"},{"name":"Animal Care Services University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Sumners","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics"},{"name":"McKnight Brain Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.08.005"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08089-3"},{"key":"e_1_2_5_4_1","first-page":"517","article-title":"Natural history of experimental intracerebral hemorrhage: sonography, computed tomography and neuropathology","volume":"2","author":"Enzmann DR","year":"1981","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02427-6"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000145485.67827.d0"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02928.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200311000-00028"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.03.010"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02105.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623311413788"},{"key":"e_1_2_5_12_1","first-page":"1","article-title":"Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence","volume":"5","author":"Lyden PD","year":"1993","journal-title":"Cerebrovasc Brain Metab Rev"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.38.1.116"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2009.047936"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2011.058578"},{"key":"e_1_2_5_16_1","first-page":"1175","article-title":"Study on Cognition and Prognosis in the Elderly study group. 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