{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:40:19Z","timestamp":1791042019334,"version":"4.1.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2009,3,11]],"date-time":"2009-03-11T00:00:00Z","timestamp":1236729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:p>\n                    Hemoproteins undergo degradation during hypoxic\/ischemic conditions, but the prooxidant free heme that is released cannot be recycled and must be degraded. The extracellular heme associates with its high-affinity binding protein, hemopexin (HPX). Hemopexin is shown here to be expressed by cortical neurons and it is present in mouse cerebellum, cortex, hippocampus, and striatum. Using the transient ischemia model (90-min middle cerebral artery occlusion followed by 96-h survival), we provide evidence that HPX is protective in the brain, as neurologic deficits and infarct volumes were significantly greater in HPX\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    than in wild-type mice. Addressing the potential protective HPX cellular pathway, we observed that exogenous free heme decreased cell survival in primary mouse cortical neuron cultures, whereas the heme bound to HPX was not toxic. Heme-HPX complexes induce HO1 and, consequently, protect primary neurons against the toxicity of both heme and prooxidant tert-butyl hydroperoxide; such protection was decreased in HO1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    neuronal cultures. Taken together, these data show that HPX protects against heme-induced toxicity and oxidative stress and that HO1 is required. We propose that the heme-HPX system protects against stroke-related damage by maintaining a tight balance between free and bound heme. Thus, regulating extracellular free heme levels, such as with HPX, could be neuroprotective.\n                  <\/jats:p>","DOI":"10.1038\/jcbfm.2009.19","type":"journal-article","created":{"date-parts":[[2009,3,11]],"date-time":"2009-03-11T05:28:28Z","timestamp":1236749308000},"page":"953-964","source":"Crossref","is-referenced-by-count":86,"title":["Heme\u2013Hemopexin Complex Attenuates Neuronal Cell Death and Stroke Damage"],"prefix":"10.1177","volume":"29","author":[{"given":"Rung-chi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiyan","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gehua","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangsen","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hean","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongseok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Biological Science, Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Altruda","sequence":"additional","affiliation":[{"name":"Department of Genetics, Biology, and Biochemistry, and the Molecular Biotechnology Center, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Tolosano","sequence":"additional","affiliation":[{"name":"Department of Genetics, Biology, and Biochemistry, and the Molecular Biotechnology Center, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Dor\u00e9","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2009,3,11]]},"reference":[{"key":"bibr1-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.01.020"},{"key":"bibr2-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84616-1"},{"key":"bibr3-jcbfm.2009.19","doi-asserted-by":"crossref","first-page":"16379","DOI":"10.1016\/S0021-9258(18)42013-3","volume":"267","author":"Alam J","year":"1992","journal-title":"J Biol Chem"},{"key":"bibr4-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1089\/152308601300185250"},{"key":"bibr5-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1080\/15216540500380871"},{"key":"bibr6-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.97.3.866"},{"key":"bibr7-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00271-6"},{"key":"bibr8-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1179\/016164106X98035"},{"key":"bibr9-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-09-03689.2003"},{"key":"bibr10-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.2174\/1567202054368344"},{"key":"bibr11-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.834"},{"key":"bibr12-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(79)91235-X"},{"key":"bibr13-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401984"},{"key":"bibr14-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2445"},{"key":"bibr15-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.2.638"},{"key":"bibr16-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2006.25.323"},{"key":"bibr17-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-007-9112-9"},{"key":"bibr18-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1042\/bj2560861"},{"key":"bibr19-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199607)168:1<71::AID-JCP9>3.0.CO;2-5"},{"key":"bibr20-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1185"},{"key":"bibr21-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00907.x"},{"key":"bibr22-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1781(96)02915-0"},{"key":"bibr23-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033275"},{"key":"bibr24-jcbfm.2009.19","doi-asserted-by":"crossref","first-page":"6256","DOI":"10.1016\/S0021-9258(18)53247-6","volume":"268","author":"Morgan WT","year":"1993","journal-title":"J Biol Chem"},{"key":"bibr25-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90756-B"},{"key":"bibr26-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1999.721187.x"},{"key":"bibr27-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105103441907"},{"key":"bibr28-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(96)00183-2"},{"key":"bibr29-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200390027"},{"key":"bibr30-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21399"},{"key":"bibr31-jcbfm.2009.19","doi-asserted-by":"crossref","unstructured":"Saleem S, Zhuang H, Biswal S, Christen Y, Dor\u00e9 S (2008)\n                      Ginkgo biloba\n                      extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke: in press","DOI":"10.1161\/STROKEAHA.108.523480"},{"key":"bibr32-jcbfm.2009.19","first-page":"839","volume":"64","author":"Saso L","year":"1999","journal-title":"Biochemistry (Mosc)"},{"key":"bibr33-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.02.066"},{"key":"bibr34-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(78)90276-0"},{"key":"bibr35-jcbfm.2009.19","doi-asserted-by":"crossref","first-page":"12049","DOI":"10.1016\/S0021-9258(20)71318-9","volume":"259","author":"Smith A","year":"1984","journal-title":"J Biol Chem"},{"key":"bibr36-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.11.3906"},{"key":"bibr37-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.635"},{"key":"bibr38-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071130"},{"key":"bibr39-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1042\/bj1670759"},{"key":"bibr40-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000073905.87928.6D"},{"key":"bibr41-jcbfm.2009.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.12.009"}],"updated-by":[{"DOI":"10.1038\/jcbfm.2014.11","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000}}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2009.19","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1038\/jcbfm.2009.19","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2009.19","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:10:50Z","timestamp":1777493450000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1038\/jcbfm.2009.19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,11]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2009,5]]}},"alternative-id":["10.1038\/jcbfm.2009.19"],"URL":"https:\/\/doi.org\/10.1038\/jcbfm.2009.19","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,11]]}}}