{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:37:47Z","timestamp":1791261467570,"version":"4.1.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury\/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month-old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells to sublethal 7-day CoCl\n              <jats:sub>2<\/jats:sub>\n              treatment to induce chemical hypoxic stress.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>Baseline myelin density in the corpus callosum was similar in 2-month and 8-month-old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in cyclic AMP response element-binding protein signaling may be involved because activating cyclic AMP response element-binding protein with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of oligodendrocyte precursor cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>An age-related decline in cyclic AMP response element-binding protein\u2013mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate cyclic AMP response element-binding protein signaling provide a potential therapeutic approach for treating white matter injury in aging brains.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.113.001530","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T17:44:25Z","timestamp":1374687865000},"page":"2573-2578","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":97,"title":["Age-Related Decline in Oligodendrogenesis Retards White Matter Repair in Mice"],"prefix":"10.1161","volume":"44","author":[{"given":"Nobukazu","family":"Miyamoto","sequence":"first","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loc-Duyen D.","family":"Pham","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hae","family":"Seo","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Magnain","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cenk","family":"Ayata","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Won","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Boas","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng H.","family":"Lo","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Arai","sequence":"additional","affiliation":[{"name":"From the Neuroprotection Research Laboratory, Departments of Radiology and Neurology (N.M., L.-D.D.P., K.H., T.M., J.H.S., E.H.L., K.A.), Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (C.M., D.B.), and Neurovascular Research Laboratory, Department of Radiology (C.A.), Massachusetts General Hospital and Harvard Medical School; and NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0b013e3182299496"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000054766"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000262306"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1735"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.07.002"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.04-06-01429.1984"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-06-02027.1996"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.11.011"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(96)00098-8"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.210"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909607106"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80359-1"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-009-9486-z"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-07-02451.2002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.10.008"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-09-03206.1998"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.20.11032"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1366.003"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1185\/030079904X4464"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70198-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.1639"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.05.013"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2009.10.008"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.113.001530","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:00:07Z","timestamp":1715608807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.113.001530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9]]},"references-count":23,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1161\/STROKEAHA.113.001530"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.113.001530","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9]]},"assertion":[{"value":"2013-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}