{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:54:50Z","timestamp":1784523290030,"version":"3.55.0"},"reference-count":67,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p> This study explored the potential effects of mild hyperhomocysteinemia (HHcy) on the blood\u2013brain barrier (BBB) and neuroinflammation. Seven-week-old male wild-type C57BL\/6 mice were fed normal mouse chow (the control group) or a methionine-enriched diet (the HHcy group) for 14 weeks. Mice in the HHcy group exhibited a slight increase in serum Hcy levels (13.56\u2009\u00b1\u20090.61 \u03bcmol\/L). Activation of the ERK signaling pathway, up-regulation of matrix metalloproteinase-9 (MMP-9), and degradation of tight junction proteins (occludin and claudin-5) were observed in both the cerebral cortex and hippocampus of mice with mild HHcy. However, microglia were not activated and the levels of tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-1\u03b2 (IL-1\u03b2) were not changed in either the cerebral cortex or hippocampus of mice with mild HHcy. Moreover, the signaling activity of STAT3 also did not differ significantly between the two groups. These findings demonstrate that the BBB is highly vulnerable to homocysteine insult. Even a slight increase in serum homocysteine levels up-regulates MMP-9 expression and disrupts the BBB integrity. Meanwhile, microglia activation or the STAT3 pathway might not contribute to the effects of mild HHcy on the brain. <\/jats:p>","DOI":"10.1139\/cjpp-2020-0507","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T18:46:26Z","timestamp":1624473986000},"page":"847-856","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Mild hyperhomocysteinemia induces blood\u2013brain barrier dysfunction but not neuroinflammation in the cerebral cortex and hippocampus of wild-type mice"],"prefix":"10.1139","volume":"99","author":[{"given":"Min","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jijun","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Urology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8326-1"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1038\/srep31545"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.6A7156.2007"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.3390\/nu9040346"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203478"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.08.015"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-338269"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.2.5.357"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.2174\/1389450117666160401120514"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000200561.69611.f8"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0963-x"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07112-z"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215472"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1124\/pr.54.4.599"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0245-0"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030393"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040867"},{"key":"refg20\/ref20","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs151"},{"key":"refg21\/ref21","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1280"},{"key":"refg22\/ref22","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7384"},{"key":"refg23\/ref23","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.1.45"},{"key":"refg24\/ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.04.018"},{"key":"refg25\/ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.07.051"},{"key":"refg26\/ref26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2506"},{"key":"refg27\/ref27","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.4.529"},{"issue":"6","key":"refg28\/ref28","first-page":"887","volume":"66","author":"Kovalska M.","year":"2015","journal-title":"J. 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