{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:37:30Z","timestamp":1788910650156,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82071331"],"award-info":[{"award-number":["82071331"]}]},{"name":"National Natural Science Foundation of China","award":["81870942"],"award-info":[{"award-number":["81870942"]}]},{"name":"National Natural Science Foundation of China","award":["81520108011"],"award-info":[{"award-number":["81520108011"]}]},{"name":"National Natural Science Foundation of China","award":["2018YFC1312200"],"award-info":[{"award-number":["2018YFC1312200"]}]},{"name":"National Key Research and Development Program of China","award":["82071331"],"award-info":[{"award-number":["82071331"]}]},{"name":"National Key Research and Development Program of China","award":["81870942"],"award-info":[{"award-number":["81870942"]}]},{"name":"National Key Research and Development Program of China","award":["81520108011"],"award-info":[{"award-number":["81520108011"]}]},{"name":"National Key Research and Development Program of China","award":["2018YFC1312200"],"award-info":[{"award-number":["2018YFC1312200"]}]},{"name":"Canadian Institutes of Health Sciences","award":["82071331"],"award-info":[{"award-number":["82071331"]}]},{"name":"Canadian Institutes of Health Sciences","award":["81870942"],"award-info":[{"award-number":["81870942"]}]},{"name":"Canadian Institutes of Health Sciences","award":["81520108011"],"award-info":[{"award-number":["81520108011"]}]},{"name":"Canadian Institutes of Health Sciences","award":["2018YFC1312200"],"award-info":[{"award-number":["2018YFC1312200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chlorogenic acid (CGA) has been reported to have various biological activities, such as anti-inflammatory, anti-oxidant and anti-apoptosis effects. However, the role of CGA in intracerebral hemorrhage (ICH) and the underlying mechanisms remain undiscovered. The current study aims to investigate the effect of CGA on neuroinflammation and neuronal apoptosis after inhibition of EMMPRIN in a collagenase-induced ICH mouse model. Dose optimization data showed that intraperitoneal administration of CGA (30 mg\/kg) significantly attenuated neurological impairments and reduced brain water content at 24 h and 72 h compared with ICH mice given vehicle. Western blot and immunofluorescence analyses revealed that CGA remarkably decreased the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in perihematomal areas at 72 h after ICH. CGA also reduced the expression of matrix metalloproteinases-2\/9 (MMP-2\/9) at 72 h after ICH. CGA diminished Evans blue dye extravasation and reduced the loss of zonula occludens-1 (ZO-1) and occludin. CGA-treated mice had fewer activated Iba-1-positive microglia and MPO-positive neutrophils. Finally, CGA suppressed cell death around the hematoma and reduced overall brain injury. These outcomes highlight that CGA treatment confers neuroprotection in ICH likely by inhibiting expression of EMMPRIN and MMP-2\/9, and alleviating neuroinflammation, blood\u2013brain barrier (BBB) disruption, cell death and brain injury.<\/jats:p>","DOI":"10.3390\/biom12081020","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T12:53:45Z","timestamp":1658494425000},"page":"1020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Neuroprotective Effects of Chlorogenic Acid in a Mouse Model of Intracerebral Hemorrhage Associated with Reduced Extracellular Matrix Metalloproteinase Inducer"],"prefix":"10.3390","volume":"12","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China"},{"name":"Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China"},{"name":"Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China"},{"name":"Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China"},{"name":"Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2600-3563","authenticated-orcid":false,"given":"Voon Wee","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4427-7285","authenticated-orcid":false,"given":"Mengzhou","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China"},{"name":"Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1474-4422(09)70340-0","article-title":"Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: A systematic review and meta-analysis","volume":"9","author":"Luitse","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"b2586","DOI":"10.1136\/bmj.b2586","article-title":"Spontaneous intracerebral haemorrhage","volume":"339","author":"Labovitz","year":"2009","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.wneu.2018.04.181","article-title":"Minimally Invasive Surgery is Superior to Conventional Craniotomy in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis","volume":"115","author":"Xia","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/S0140-6736(19)30195-3","article-title":"Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): A randomised, controlled, open-label, blinded endpoint phase 3 trial","volume":"393","author":"Hanley","year":"2019","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"847246","DOI":"10.3389\/fimmu.2022.847246","article-title":"Oxidative Stress Following Intracerebral Hemorrhage: From Molecular Mechanisms to Therapeutic Targets","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. 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