Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage
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 12–39% achieve good outcomes and functional independence. ICH affects nearly 2 million patients worldwide annually. In ICH development, the...
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MDPI AG
2021-12-01
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| author | Yan Zhang Suliman Khan Yang Liu Rabeea Siddique Ruiyi Zhang Voon Wee Yong Mengzhou Xue |
| author_facet | Yan Zhang Suliman Khan Yang Liu Rabeea Siddique Ruiyi Zhang Voon Wee Yong Mengzhou Xue |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | 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 12–39% 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. |
| first_indexed | 2024-03-10T01:53:55Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T01:53:55Z |
| publishDate | 2021-12-01 |
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| spelling | doaj.art-518dafdd22f64e0ea7b01631a9a1f94e2023-11-23T12:59:55ZengMDPI AGBiology2079-77372021-12-011112710.3390/biology11010027Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral HemorrhageYan Zhang0Suliman Khan1Yang Liu2Rabeea Siddique3Ruiyi Zhang4Voon Wee Yong5Mengzhou Xue6Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaDepartment of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaDepartment of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaDepartment of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaDepartment of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaHotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T3A 4X9, CanadaDepartment of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaIntracerebral 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 12–39% 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.https://www.mdpi.com/2079-7737/11/1/27intracerebral hemorrhagesecondary brain injurypannexinhemichannelinflammationoxidative stress |
| spellingShingle | Yan Zhang Suliman Khan Yang Liu Rabeea Siddique Ruiyi Zhang Voon Wee Yong Mengzhou Xue Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage Biology intracerebral hemorrhage secondary brain injury pannexin hemichannel inflammation oxidative stress |
| title | Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage |
| title_full | Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage |
| title_fullStr | Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage |
| title_full_unstemmed | Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage |
| title_short | Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage |
| title_sort | gap junctions and hemichannels composed of connexins and pannexins mediate the secondary brain injury following intracerebral hemorrhage |
| topic | intracerebral hemorrhage secondary brain injury pannexin hemichannel inflammation oxidative stress |
| url | https://www.mdpi.com/2079-7737/11/1/27 |
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