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U.S.A."],"published-print":{"date-parts":[[2017,4,4]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Six million people die each year from stroke, and 5 million survivors are left with a permanent disability. Moreover, the neuronal damage caused by stroke often triggers a progressive decline in cognitive function that doubles the risk of dementia for stroke survivors. Despite this massive global disease burden, there are no approved drugs for treating the neuronal injury caused to the brain by the oxygen deprivation occurring during an ischemic stroke. The precipitous drop in brain pH resulting from stroke activates acid-sensing ion channel 1a. We show that inhibition of these channels using a \u201cdouble-knot\u201d spider venom peptide massively attenuates brain damage after stroke and improves behavioral outcomes, even when the peptide is administered 8 h after stroke onset.<\/jats:p>","DOI":"10.1073\/pnas.1614728114","type":"journal-article","created":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T20:55:39Z","timestamp":1490043339000},"page":"3750-3755","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":227,"title":["Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a"],"prefix":"10.1073","volume":"114","author":[{"given":"Ir\u00e8ne R.","family":"Chassagnon","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;"},{"name":"Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni K.-Y.","family":"Chin","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy S.","family":"Pineda","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2846-052X","authenticated-orcid":false,"given":"Angelo","family":"Keramidas","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Mobli","sequence":"additional","affiliation":[{"name":"Centre for Advanced Imaging, The University of Queensland, St. Lucia, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vi","family":"Pham","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;"},{"name":"Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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J Gen Physiol 127, 267\u2013276 (2006).","journal-title":"J Gen Physiol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1110\/ps.0307003","article-title":"Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels","volume":"12","author":"Escoubas P","year":"2003","unstructured":"P Escoubas, C Bernard, G Lambeau, M Lazdunski, H Darbon, Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein Sci 12, 1332\u20131343 (2003).","journal-title":"Protein Sci"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev-ento-120811-153650","article-title":"Spider-venom peptides: Structure, pharmacology, and potential for control of insect pests","volume":"58","author":"King GF","year":"2013","unstructured":"GF King, MC Hardy, Spider-venom peptides: Structure, pharmacology, and potential for control of insect pests. Annu Rev Entomol 58, 475\u2013496 (2013).","journal-title":"Annu Rev Entomol"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1038\/ncomms5350","article-title":"A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a","volume":"5","author":"Bende NS","year":"2014","unstructured":"NS Bende, , A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a. 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J Biol Chem 284, 27899\u201327907 (2009).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0140-6736(13)61953-4","article-title":"Global and regional burden of stroke during 1990-2010: Findings from the Global Burden of Disease Study 2010","volume":"383","author":"Feigin VL","year":"2014","unstructured":"VL Feigin, , Global and regional burden of stroke during 1990-2010: Findings from the Global Burden of Disease Study 2010. Lancet; Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) and the GBD Stroke Experts Group 383, 245\u2013254 (2014).","journal-title":"Lancet"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev.med.53.082901.104106","article-title":"Ischemic stroke therapy","volume":"53","author":"Stapf C","year":"2002","unstructured":"C Stapf, JP Mohr, Ischemic stroke therapy. Annu Rev Med 53, 453\u2013475 (2002).","journal-title":"Annu Rev Med"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1161\/01.STR.0000125860.48180.48","article-title":"International comparison of stroke cost studies","volume":"35","author":"Evers SM","year":"2004","unstructured":"SM Evers, , International comparison of stroke cost studies. Stroke 35, 1209\u20131215 (2004).","journal-title":"Stroke"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.tips.2008.02.003","article-title":"Beyond NMDA and AMPA glutamate receptors: Emerging mechanisms for ionic imbalance and cell death in stroke","volume":"29","author":"Besancon E","year":"2008","unstructured":"E Besancon, S Guo, J Lok, M Tymianski, EH Lo, Beyond NMDA and AMPA glutamate receptors: Emerging mechanisms for ionic imbalance and cell death in stroke. Trends Pharmacol Sci 29, 268\u2013275 (2008).","journal-title":"Trends Pharmacol Sci"},{"key":"e_1_3_4_31_2","first-page":"75","article-title":"Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke","volume":"10","author":"Chapman SN","year":"2014","unstructured":"SN Chapman, , Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke. Vasc Health Risk Manag 10, 75\u201387 (2014).","journal-title":"Vasc Health Risk Manag"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.toxicon.2013.04.008","article-title":"Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels","volume":"75","author":"Baron A","year":"2013","unstructured":"A Baron, , Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. Toxicon 75, 187\u2013204 (2013).","journal-title":"Toxicon"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/mrm.1263","article-title":"A serial MR study of cerebral blood flow changes and lesion development following endothelin-1\u2013induced ischemia in rats","volume":"46","author":"Biernaskie J","year":"2001","unstructured":"J Biernaskie, D Corbett, J Peeling, J Wells, H Lei, A serial MR study of cerebral blood flow changes and lesion development following endothelin-1\u2013induced ischemia in rats. Magn Reson Med 46, 827\u2013830 (2001).","journal-title":"Magn Reson Med"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1113\/expphysiol.2009.047936","article-title":"Candesartan pretreatment is cerebroprotective in a rat model of endothelin-1\u2013induced middle cerebral artery occlusion","volume":"94","author":"Mecca AP","year":"2009","unstructured":"AP Mecca, TE O\u2019Connor, MJ Katovich, C Sumners, Candesartan pretreatment is cerebroprotective in a rat model of endothelin-1\u2013induced middle cerebral artery occlusion. Exp Physiol 94, 937\u2013946 (2009).","journal-title":"Exp Physiol"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.neulet.2008.09.006","article-title":"Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats","volume":"445","author":"Glendenning ML","year":"2008","unstructured":"ML Glendenning, T Lovekamp-Swan, DA Schreihofer, Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats. Neurosci Lett 445, 188\u2013192 (2008).","journal-title":"Neurosci Lett"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"e05682","DOI":"10.7554\/eLife.05682","article-title":"Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction","volume":"4","author":"Wang YZ","year":"2015","unstructured":"YZ Wang, , Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction. eLife 4, e05682 (2015).","journal-title":"eLife"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-physiol-021113-170259","article-title":"Control of life-or-death decisions by RIP1 kinase","volume":"76","author":"Christofferson DE","year":"2014","unstructured":"DE Christofferson, Y Li, J Yuan, Control of life-or-death decisions by RIP1 kinase. Annu Rev Physiol 76, 129\u2013150 (2014).","journal-title":"Annu Rev Physiol"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nchembio711","article-title":"Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury","volume":"1","author":"Degterev A","year":"2005","unstructured":"A Degterev, , Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1, 112\u2013119 (2005).","journal-title":"Nat Chem Biol"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1101\/gr.1917404","article-title":"Using the miraEST assembler for reliable and automated mRNA transcript assembly and SNP detection in sequenced ESTs","volume":"14","author":"Chevreux B","year":"2004","unstructured":"B Chevreux, , Using the miraEST assembler for reliable and automated mRNA transcript assembly and SNP detection in sequenced ESTs. 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