{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T15:47:25Z","timestamp":1782575245466,"version":"3.54.5"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            Hypoxic preconditioning (PC) confers robust neuroprotection against neonatal hypoxic-ischemic brain injury (H-I), yet the underlying mechanism is poorly understood. In the adult brain, neuronal survival after ischemia is associated with the activation of the phosphatidylinositol 3-kinase (PI3-K)\/Akt signaling pathway. Suppression of inflammation is a newly identified direct consequence of PI3-K\/Akt signaling. We therefore investigated whether PI3-K\/Akt suppresses inflammation and contributes to PC-induced neuroprotection.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            Postnatal day 7 rats were exposed for 3 hours to either ambient air or 8% oxygen, which induces hypoxic PC. H-I was produced 24 hours later by unilateral carotid artery ligation followed by 2.5 hours of hypoxia. Animals were euthanized 0 to 24 hours later for detecting Akt and glycogen synthetase kinase-3\u03b2 phosphorylation (p-Akt, p-GSK-3\u03b2), 24 hours later for assessing cytokine expression and inflammatory markers, and 7 days later for measuring brain tissue loss. In addition, LY294002 was injected intracerebroventricularly to inhibit PI3-K\/Akt.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Brains with H-I without PC showed delayed but sustained reduction in p-Akt. PC restored the levels of p-Akt and the Akt substrate GSK-3\u03b2, reduced proinflammatory markers (NF-\u03baB, COX-2, CD68, myeloperoxidase, and microglial activation), and markedly ameliorated H-I-induced brain tissue loss. Inhibition of PI3-K\/Akt using LY294002 attenuated PC neuroprotection and promoted the expression of NF-\u03baB, COX-2, and CD68. Proteomic microarray analysis revealed that PC inhibited expression of proinflammatory cytokines induced by H-I or a dose of lipopolysaccharide that resulted in minimal tissue damage.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Suppression of inflammatory responses may contribute to PC neuroprotection against neonatal H-I brain injury. This effect is mediated in part via upregulating PI3-K\/Akt activity.\n          <\/jats:p>","DOI":"10.1161\/01.str.0000258102.18836.ca","type":"journal-article","created":{"date-parts":[[2007,2,3]],"date-time":"2007-02-03T06:46:52Z","timestamp":1170485212000},"page":"1017-1024","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Preconditioning Suppresses Inflammation in Neonatal Hypoxic Ischemia Via Akt Activation"],"prefix":"10.1161","volume":"38","author":[{"given":"Wei","family":"Yin","sequence":"first","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando P.","family":"Signore","sequence":"additional","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Iwai","sequence":"additional","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Cao","sequence":"additional","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Gao","sequence":"additional","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Johnnides","sequence":"additional","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Hickey","sequence":"additional","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"From Department of Neurology (W.Y., A.P.S., M.I., G.C., M.J.J., R.W.H., J.C.) and Institute of Neurodegenerative Diseases (A.P.S., G.C., J.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pa; State Key Laboratory of Medical Neurobiology (G.C., Y.C., J.C.), Fudan University School of Medicine, Shanghai, China; Division of Pediatric Emergency Medicine (R.W.H.), Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pa; Geriatric Research (J.C.), Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.9.1916"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199908000-00001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2000.tb00247.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90455-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000085979"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199702000-00007"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200104000-00004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06401.2002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203298200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000166180.91042.02"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02324.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410090206"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200111000-00010"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410416"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00377-7"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.07.015"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.01.074"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(01)00024-7"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199705000-00002"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02120.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000145666.68576.71"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/35017574"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.19.8444-8455.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00495.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1019-05.2005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20259"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03639.x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02547.x"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.STR.0000258102.18836.ca","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T21:45:47Z","timestamp":1715550347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.STR.0000258102.18836.ca"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,3]]}},"alternative-id":["10.1161\/01.STR.0000258102.18836.ca"],"URL":"https:\/\/doi.org\/10.1161\/01.str.0000258102.18836.ca","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3]]},"assertion":[{"value":"2006-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}