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One strategy to reduce SCI morbidity involves limiting the spread of secondary damage after injury. Previous studies have shown that connexin 43 (Cx43), a gap junction protein richly expressed in spinal cord astrocytes, is a potential mediator of secondary damage. Here, we developed a specific inhibitory antibody, mouse-human chimeric MHC1 antibody (MHC1), that inhibited Cx43 hemichannels, but not gap junctions, and reduced secondary damage in 2 incomplete SCI mouse models. MHC1 inhibited the activation of Cx43 hemichannels in both primary spinal astrocytes and astrocytes in situ. In both SCI mouse models, administration of MHC1 after SCI significantly improved hind limb locomotion function. Remarkably, a single administration of MHC1 30 minutes after injury improved the recovery up to 8 weeks post-SCI. Moreover, MHC1 treatment decreased gliosis and lesion sizes, increased white and gray matter sparing, and improved neuronal survival. Together, these results suggest that inhibition of Cx43 hemichannel function after traumatic SCI reduces secondary damage, limits perilesional gliosis, and improves functional recovery. By targeting hemichannels specifically with an antibody, this study provides a potentially new, innovative therapeutic approach in treating SCI.<\/jats:p>","DOI":"10.1172\/jci.insight.134611","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T14:01:15Z","timestamp":1615125675000},"source":"Crossref","is-referenced-by-count":46,"title":["Inhibition of astrocyte hemichannel improves recovery from spinal cord injury"],"prefix":"10.1172","volume":"6","author":[{"given":"Chao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."},{"name":"The Second Xiangya Hospital of Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."},{"name":"The Second Xiangya Hospital of Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Maknojia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1915-0434","authenticated-orcid":true,"given":"Manuel A.","family":"Riquelme","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Booher","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3606-591X","authenticated-orcid":true,"given":"David J.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Bartanusz","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-9270","authenticated-orcid":true,"given":"Akshay","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Mader","sequence":"additional","affiliation":[{"name":"Audie L. 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