{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:22:30Z","timestamp":1790680950105,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background and Purpose\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Emerging evidence suggests that mitochondrial damage\u2013mediated neuronal apoptosis is a major contributor to neonatal hypoxic-ischemic (H-I) brain injury. This study was performed to determine whether targeted inhibition of the apoptotic protease activating factor-1 (Apaf-1) signaling pathway downstream of mitochondrial damage confers neuroprotection in rodent models of neonatal H-I.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    H-I was induced in 7-day-old (P7) transgenic mice overexpressing the specific Apaf-1\u2013inhibitory protein AIP. Apaf-1 inhibition was also achieved in P7 rats by protein transduction\u2013enhanced delivery of recombinant AIP. Pups were euthanized 6 to 24 hours after H-I for assessing caspase activation and mitochondrial release of cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    and AIF, and 7 days after H-I for analyzing brain tissue damage. Sensorimotor functions were assessed in rats up to 4 weeks after H-I.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Transgenic overexpression of AIP protected against H-I brain injury, resulting in attenuated activation of caspase-9 and caspase-3, and attenuated brain tissue loss. In neonatal H-I rats, intraperitoneal injection of TAT-AIP, but not the control proteins TAT-GFP or AIP, decreased caspase activation and brain damage and improved neurological functions. Neuroprotection conferred by AIP was also associated with significantly reduced release of cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    and AIF from mitochondria.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusion\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The Apaf-1 signaling pathway, which transmits cell death signals after mitochondrial damage to effector caspases, may be a legitimate therapeutic target for the treatment of neonatal H-I brain injury.\n                  <\/jats:p>","DOI":"10.1161\/strokeaha.109.561852","type":"journal-article","created":{"date-parts":[[2009,11,12]],"date-time":"2009-11-12T22:20:16Z","timestamp":1258064416000},"page":"166-172","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Neuroprotection Against Hypoxic-Ischemic Brain Injury by Inhibiting the Apoptotic Protease Activating Factor-1 Pathway"],"prefix":"10.1161","volume":"41","author":[{"given":"Yanqin","family":"Gao","sequence":"first","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Liang","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Hu","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Anne","family":"Stetler","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vosler","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Cao","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital (Y.G., W.L., W.Z., R.A.S., G.C., J.C.), Fudan University School of Medicine, Shanghai, China; and the Center of Cerebrovascular Disease Research (Y.G., X.H., W.Z., R.A.S., P.V., G.C., J.C.), University of Pittsburgh School of Medicine, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-21-07994.2000"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-06-01931.2001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410416"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200009000-00003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80434-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.13.3586"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200105000-00010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1426-04.2004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.07.015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-13-05423.2002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.107.483008"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00892-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200207071"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402053"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204991200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2826-07.2007"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413269200"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2169"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2003.12.029"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2981fje"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1046\/j.1471-4159.2003.01832.x","volume":"86","year":"2003","unstructured":"Zhu C, Qiu L, Wang X, Hallin U, Cande C, Kroemer G, Hagberg H, Blomgren K. Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain. 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