{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T18:59:07Z","timestamp":1772305147210,"version":"3.50.1"},"reference-count":59,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["DK069632"],"award-info":[{"award-number":["DK069632"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:p>Stroke-prone spontaneously hypertensive rats (SHR-A3) develop strokes and progressive kidney disease as a result of naturally occurring genetic variations. We recently identified genetic variants in immune signaling pathways that contribute to end-organ injury. The present study was designed to test the hypothesis that a dysregulated immune response promotes stroke susceptibility. We salt-loaded 20 wk old male SHR-A3 rats and treated them with the immunosuppressant mycophenolate mofetil (MMF, 25 mg\/kg\/day po) ( n = 8) or vehicle (saline) ( n = 9) for 8 wk. Blood pressure (BP) was measured weekly by telemetry. Compared with vehicle-treated controls, MMF-treated SHR-A3 rats had improved survival and lower neurological deficit scores (1.44 vs. 0.125; P &lt; 0.02). Gross morphology of the brain revealed cerebral edema in 8 of 9, and microbleeds and hemorrhages in 5 of 9 vehicle-treated rats. These lesions were absent in MMF-treated rats. Brain CD68 expression, indicating macrophage\/microglial activation, was upregulated in vehicle-treated rats with microbleeds and hemorrhages but was undetectable in the brains of MMF-treated rats. MMF also prevented renal injury in SHR-A3 rats, evidenced by reduced proteinuria (albumin:creatinine) from 7.52 to 1.05 mg\/mg ( P &lt; 0.03) and lower tubulointerstitial injury scores (2.46 vs. 1.43; P &lt; 0.01). Salt loading resulted in a progressive increase in BP, which was blunted in rats receiving MMF. Our findings provide evidence that abnormal immune activation predisposes to cerebrovascular and renal injury in stroke-prone SHR-A3 rats.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00110.2016","type":"journal-article","created":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T03:00:40Z","timestamp":1482548440000},"page":"132-140","source":"Crossref","is-referenced-by-count":8,"title":["Mycophenolate mofetil prevents cerebrovascular injury in stroke-prone spontaneously hypertensive rats"],"prefix":"10.1152","volume":"49","author":[{"given":"Isha S.","family":"Dhande","sequence":"first","affiliation":[{"name":"Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaming","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. John","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-8277","authenticated-orcid":false,"given":"Scott E.","family":"Wenderfer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Doris","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.18.547"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.110.958934"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.1.167"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2010.05428.x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328362f9a5"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.000533"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.07.048"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00298.2009"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600495"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000177498.21594.9e"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.009990"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-89"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2004.07.004"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000090841.90286.81"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00221.2006"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00463.2012"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.510800"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.1.170"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00138.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.534503"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000084635.01667.8A"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2014.40"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.8.1599"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(00)01282-6"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/hs0302.104111"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/14.1.58"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-3274(96)80039-6"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.246"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006080918"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010111148"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009128"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900094"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-006-0406-6"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.7.1361"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000228320.23697.29"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.08.019"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5376-06.2007"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000046"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023161"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199911000-00008"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.27.11.2033"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007121271"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1023\/B:CEMN.0000036402.79129.2f"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2012.30"},{"key":"B45","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1152\/ajplegacy.1976.230.5.1354","volume":"230","author":"Nagaoka A","year":"1976","journal-title":"Am J Physiol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.2.487"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.08.032"},{"key":"B48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1161\/01.RES.34.2.143","volume":"34","author":"Okamoto KY","year":"1974","journal-title":"Circ Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00821.2007"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.1.F38"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00737.x"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.055003945.x"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009861"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00082-7"},{"key":"B55","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0022-3565(24)35140-7","volume":"291","author":"Smeda J","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00487.2006"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.517284"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.8.4.456"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.7.1.46"}],"container-title":["Physiological Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/physiolgenomics.00110.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T21:00:53Z","timestamp":1749848453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/physiolgenomics.00110.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,1]]},"references-count":59,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3,1]]}},"alternative-id":["10.1152\/physiolgenomics.00110.2016"],"URL":"https:\/\/doi.org\/10.1152\/physiolgenomics.00110.2016","relation":{},"ISSN":["1094-8341","1531-2267"],"issn-type":[{"value":"1094-8341","type":"print"},{"value":"1531-2267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,1]]}}}