{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:41:57Z","timestamp":1780105317236,"version":"3.54.0"},"update-to":[{"DOI":"10.12688\/f1000research.9094.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T00:00:00Z","timestamp":1481068800000}}],"reference-count":74,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T00:00:00Z","timestamp":1481068800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Tissue loss after spinal trauma is biphasic, with initial mechanical\/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a \u201c\n                    <ns4:italic>treatment window<\/ns4:italic>\n                    \u201d through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.9094.2","type":"journal-article","created":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T06:35:13Z","timestamp":1481092513000},"page":"1822","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury"],"prefix":"10.12688","volume":"5","author":[{"given":"Liam M.","family":"Koehn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natassya 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.11107.r18324, David Magnuson, Darlene Burke, Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, USA, 19 Dec 2016, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/5-1822\/v2#referee-response-18324","order":0,"name":"referee-response-18324","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.9788.r15249, Helen Marie Bramlett, Department of Neurological Surgery, University of Miami, Miami, FL, USA, 30 Sep 2016, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/5-1822\/v1#referee-response-15249","order":1,"name":"referee-response-15249","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Mark Habgood<\/b>; \n<i>Posted: 22 Nov 2016<\/i>; \n<i>&quot;The authors state that the use of the osmotic pump for PcTx1 release resulted in stable plasma concentrations of the drug over a 48 hr period, how was this determined?&nbsp;Were levels taken or was this an assumption?&quot;<\/i>  Yes this was an assumption. The role of the pump was to slowly and steadily release PcTx1 (1.08 \u03bcg\/h) subcutaneously to compensate for estimated renal and tissue losses over a 48 h period. &nbsp; PcTx1 is a cysteine knot peptide which makes it very stable and resistant to plasma peptidases with a half-life &gt;12 hours (unpublished). Thus, \n<i>in vivo<\/i>, the main plasma losses are due to renal excretion  \n<i>&quot;Pre-training&quot;<\/i>  The animals were pre-trained on the beam apparatus prior to commencement of the surgical and treatment protocols. On the day of functional testing, the animals were allowed 3 practice runs prior to recording. This information has been added to the Methods.","URL":"https:\/\/f1000research.com\/articles\/5-1822\/v2#referee-comment-2303","order":2,"name":"referee-comment-2303","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Australian National Health & Medical Research Council (NHMRC) Project Grant APP1049287 to M.D.H and N.R.S, Project Grant APP1063798 to G.F.K. and a NHMRC Principal Research Fellowship to G.F.K. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}