Systemic Administration of Connexin43 Mimetic Peptide Improves Functional Recovery after Traumatic Spinal Cord Injury in Adult Rats

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dc.contributor.author Mao, Y en
dc.contributor.author Tonkin, RS en
dc.contributor.author Nguyen, T en
dc.contributor.author OCarroll, Simon en
dc.contributor.author Nicholson, Louise en
dc.contributor.author Green, Colin en
dc.contributor.author Moalem-Taylor, G en
dc.contributor.author Gorrie, CA en
dc.date.accessioned 2017-05-29T22:46:47Z en
dc.date.issued 2017-02-01 en
dc.identifier.citation Journal of neurotrauma, 01 February 2017, 34 (3), 707 - 719 en
dc.identifier.issn 0897-7151 en
dc.identifier.uri http://hdl.handle.net/2292/33159 en
dc.description.abstract Blocking of Connexin43 hemichannels, the main gap junction protein located on astrocytes in the central nervous system, has been shown to reduce neural injury in a number of models. We demonstrated previously that local administration of a Connexin43 mimetic peptide, Peptide5, reduces secondary tissue damage after spinal cord injury (SCI). Here, we investigated whether acute systemic delivery of Peptide5 is also protective in a model of SCI. Rats were subjected to a mild spinal cord contusion using the Multicentre Animal Spinal Cord Injury Study impactor and were injected intraperitoneally with Peptide5 or a scrambled peptide immediately and at 2 h and 4 h post-injury. Rats were tested for locomotor recovery and pain hypersensitivity and euthanized at 8 h, 24 h, two weeks, or six weeks post-injury. Compared with control rats, Peptide5 treated rats showed significant improvement in hindlimb locomotor function between three and six weeks post-injury and reductions in at-level mechanical allodynia at weeks one and six post-injury. Immunohistochemistry showed that Peptide5 treatment led to a reduction in total Connexin43 and increased phosphorylated Connexin43 at 8 h compared with scrambled peptide. At two and six weeks, lesion size, the astrocytic and the activated macrophage, and/or microglial response were all decreased in the Peptide5 animals. In addition, neuronal cell numbers were higher in the Peptide5 animals compared with the scrambled peptide treated rats at two and six weeks. These results show for the first time that systemic administration of Peptide5 to block the pathological opening of Connexin43 hemichannels is a feasible treatment strategy in this setting, ameliorating the secondary SCI. en
dc.description.uri https://www.ncbi.nlm.nih.gov/pubmed/27629792 en
dc.format.medium Print-Electronic en
dc.language English en
dc.publisher Liebert en
dc.relation.ispartofseries Journal of neurotrauma en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://sherpa.ac.uk/romeo/issn/0897-7151/ http://www.liebertpub.com/nv/resources-tools/self-archiving/51/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Systemic Administration of Connexin43 Mimetic Peptide Improves Functional Recovery after Traumatic Spinal Cord Injury in Adult Rats en
dc.type Journal Article en
dc.identifier.doi 10.1089/neu.2016.4625 en
pubs.issue 3 en
pubs.begin-page 707 en
pubs.volume 34 en
dc.description.version VoR - Version of Record en
dc.identifier.pmid 27629792 en
pubs.author-url http://online.liebertpub.com/doi/10.1089/neu.2016.4625 en
pubs.end-page 719 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 541310 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Anatomy and Medical Imaging en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1557-9042 en
pubs.record-created-at-source-date 2017-05-30 en
pubs.online-publication-date 2016-10-13 en
pubs.dimensions-id 27629792 en


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