Dose-dependent protective effect of connexin43 mimetic peptide against neurodegeneration in an ex vivo model of epileptiform lesion

Show simple item record Yoon, Jinny en Green, Colin en OCarroll, Simon en Nicholson, Louise en
dc.coverage.spatial Netherlands en 2011-11-17T17:19:42Z en 2010-12 en
dc.identifier.citation Epilepsy Res 92(2-3):153-162 Dec 2010 en
dc.identifier.issn 0920-1211 en
dc.identifier.uri en
dc.description.abstract Epileptic seizures typically result in delayed neuronal loss secondary to the initial damage and an up-regulation in connexin43 (Cx43). This study investigated the role of Cx43 gap junctions in lesion spread and cell loss following epileptiform activity. Epileptiform injury in hippocampal slice cultures was induced by 48 h exposure to 100 μM bicuculline methochloride (BMC). During the 24h recovery period following BMC treatment, lesion spread was observed in the CA1. A Cx43 mimetic peptide, applied during either the BMC treatment or recovery periods, produced concentration- and exposure time-dependent neuroprotection, as measured by propidium iodide uptake at the end of the recovery period. During the BMC period, peptide concentrations between 5 and 50 μM (sufficient to block hemichannels) had a protective effect while a substantial gap junction blockade with 500 μM peptide exacerbated the lesion. By contrast, all doses applied during the recovery period protected the CA1 region from further damage. The results indicate that while the slices are undergoing excessive neuronal firing and epileptic stress, gap junction communication appears to be essential for tissue survival but hemichannel opening may be damaging. Following epileptiform insult, however, gap junction communication plays a crucial role in the spread of neuronal damage. The findings from this study identify gap junction communication as a potential therapeutic target for epilepsy. en
dc.language eng en
dc.relation.ispartofseries Epilepsy Research 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 en
dc.rights.uri en
dc.subject Animals en
dc.subject Animals, Newborn en
dc.subject Bicuculline en
dc.subject CA1 Region, Hippocampal en
dc.subject Cell Death en
dc.subject Connexin 43 en
dc.subject Culture Media, Serum-Free en
dc.subject Dose-Response Relationship, Drug en
dc.subject GABA Antagonists en
dc.subject Microtubule-Associated Proteins en
dc.subject Nerve Degeneration en
dc.subject Peptides en
dc.subject Rats en
dc.subject Rats, Wistar en
dc.subject Time Factors en
dc.title Dose-dependent protective effect of connexin43 mimetic peptide against neurodegeneration in an ex vivo model of epileptiform lesion en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.eplepsyres.2010.08.014 en
pubs.issue 2-3 en
pubs.begin-page 153 en
pubs.volume 92 en
dc.rights.holder Copyright: 2010 Elsevier B.V. en
dc.identifier.pmid 20851574 en en
pubs.end-page 162 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 151641 en Medical and Health Sciences en Medical Sciences en Anatomy and Medical Imaging en School of Medicine en Ophthalmology Department en Science en Science Research en Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1872-6844 en
dc.identifier.pii S0920-1211(10)00240-8 en
pubs.record-created-at-source-date 2011-05-18 en
pubs.dimensions-id 20851574 en

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