{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:10:07Z","timestamp":1792789807901,"version":"4.5.0"},"reference-count":76,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T00:00:00Z","timestamp":1640390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071331, 81870942, and 81520108011"],"award-info":[{"award-number":["82071331, 81870942, and 81520108011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1312200"],"award-info":[{"award-number":["2018YFC1312200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Institutes of Health Sciences","award":["VWY"],"award-info":[{"award-number":["VWY"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity; the mortality rate ranges from 40% at 1 month to 54% at 1 year; only 12\u201339% achieve good outcomes and functional independence. ICH affects nearly 2 million patients worldwide annually. In ICH development, the blood leakage from ruptured vessels generates sequelae of secondary brain injury (SBI). This mechanism involves activated astrocytes and microglia, generation of reactive oxygen species (ROS), the release of reactive nitrogen species (RNS), and disrupted blood brain barrier (BBB). In addition, inflammatory cytokines and chemokines, heme compounds, and products of hematoma are accumulated in the extracellular spaces, thereby resulting in the death of brain cells. Recent evidence indicates that connexins regulate microglial activation and their phenotypic transformation. Moreover, communications between neurons and glia via gap junctions have crucial roles in neuroinflammation and cell death. A growing body of evidence suggests that, in addition to gap junctions, hemichannels (composed of connexins and pannexins) play a key role in ICH pathogenesis. However, the precise connection between connexin and pannexin channels and ICH remains to be resolved. This review discusses the pathological roles of gap junctions and hemichannels in SBI following ICH, with the intent of discovering effective therapeutic options of strategies to treat ICH.<\/jats:p>","DOI":"10.3390\/biology11010027","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage"],"prefix":"10.3390","volume":"11","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China"},{"name":"Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-0748","authenticated-orcid":false,"given":"Suliman","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China"},{"name":"Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China"},{"name":"Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabeea","family":"Siddique","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China"},{"name":"Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China"},{"name":"Academy of Medical Science, Zhengzhou University, 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":"Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T3A 4X9, 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 450014, China"},{"name":"Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1001\/jama.2019.2413","article-title":"Cerebral Intraparenchymal Hemorrhage: A Review","volume":"321","author":"Gross","year":"2019","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"232","DOI":"10.26599\/JNR.2020.9040024","article-title":"Clinical Neurorestorative Therapeutic Guideline for Brainstem Hemorrhage (2020 China Version)","volume":"8","author":"Chen","year":"2020","journal-title":"J. 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