{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T16:28:18Z","timestamp":1792340898579,"version":"4.4.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,3,18]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The blood\u2013spinal cord barrier (BSCB) is damaged in human ALS and rodents expressing ALS-associated superoxide dismutase mutations. The role of BSCB breakdown in disease pathogenesis remains, however, unclear. Early motor-neuron dysfunction and injury are now shown to be proportional to the degree of BSCB disruption, and early protection of the BSCB integrity with an activated protein C analog is found to delay onset of motor-neuron impairment and degeneration. Altogether, these findings in mice show that BSCB breakdown plays a role in early-stage disease pathogenesis and that restoring BSCB integrity retards the disease process. These findings are relevant to the corresponding disease mechanism in human ALS in which ALS-associated vascular pathology is associated.<\/jats:p>","DOI":"10.1073\/pnas.1401595111","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T21:26:27Z","timestamp":1393881987000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":225,"title":["Blood\u2013spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice"],"prefix":"10.1073","volume":"111","author":[{"given":"Ethan A.","family":"Winkler","sequence":"first","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"},{"name":"School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse D.","family":"Sengillo","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay P.","family":"Sagare","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyi","family":"Ma","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Zuniga","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoming","family":"Wang","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Zhong","sequence":"additional","affiliation":[{"name":"National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don W.","family":"Cleveland","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berislav V.","family":"Zlokovic","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Center for Neurodegeneration and Regeneration, Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA 90089;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,3,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3114"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61156-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1039-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a41228"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22594"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.189.3.8234713"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035241"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001205"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2073"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.09.018"},{"key":"e_1_3_3_11_2","first-page":"3437","article-title":"Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells","volume":"119","author":"Zhong Z","year":"2009","unstructured":"Z Zhong, et al., Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells. J Clin Invest 119, 3437\u20133449 (2009).","journal-title":"J Clin Invest"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.155"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09522"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.043"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11087"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.10.1095"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.517482"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.035972"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.2104"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1998.15.645"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123511"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607423103"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1885"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1876"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2047"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1957"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086071"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.3945\/an.111.001784"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04531.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705044104"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2660"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.011"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035050"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705824200"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.01.005"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-003004"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5443-08.2009"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.09.056"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.04.025"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1205"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003209"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg312"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715760290029128"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1498"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1401595111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:37:27Z","timestamp":1649806647000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1401595111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,3]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,3,18]]}},"alternative-id":["10.1073\/pnas.1401595111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1401595111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,3]]},"assertion":[{"value":"2014-03-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}