{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:18:50Z","timestamp":1773418730610,"version":"3.50.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg\/kg or 1 mg\/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg\/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor\u2013TrkB signaling in the immature brain.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.113.001552","type":"journal-article","created":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T06:51:50Z","timestamp":1369810310000},"page":"2275-2283","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Thyroxin Treatment Protects Against White Matter Injury in The Immature Brain via Brain-Derived Neurotrophic Factor"],"prefix":"10.1161","volume":"44","author":[{"given":"Pi-Lien","family":"Hung","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics and Graduate Institute of Clinical Medicine Sciences (P.-L.H., Y.-C.C.) and Ophthalmology (H.-M.H.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute of Clinical Medicine and Department of Pediatrics, National Cheng Kung University College of Medicine, Tainan, Taiwan (C.-C.H.); and Department of Nuclear Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan (D.-G.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics and Graduate Institute of Clinical Medicine Sciences (P.-L.H., Y.-C.C.) and Ophthalmology (H.-M.H.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute of Clinical Medicine and Department of Pediatrics, National Cheng Kung University College of Medicine, Tainan, Taiwan (C.-C.H.); and Department of Nuclear Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan (D.-G.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Mei","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics and Graduate Institute of Clinical Medicine Sciences (P.-L.H., Y.-C.C.) and Ophthalmology (H.-M.H.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute of Clinical Medicine and Department of Pediatrics, National Cheng Kung University College of Medicine, Tainan, Taiwan (C.-C.H.); and Department of Nuclear Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan (D.-G.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dom-Gene","family":"Tu","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics and Graduate Institute of Clinical Medicine Sciences (P.-L.H., Y.-C.C.) and Ophthalmology (H.-M.H.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute of Clinical Medicine and Department of Pediatrics, National Cheng Kung University College of Medicine, Tainan, Taiwan (C.-C.H.); and Department of Nuclear Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan (D.-G.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics and Graduate Institute of Clinical Medicine Sciences (P.-L.H., Y.-C.C.) and Ophthalmology (H.-M.H.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute of Clinical Medicine and Department of Pediatrics, National Cheng Kung University College of Medicine, Tainan, Taiwan (C.-C.H.); and Department of Nuclear Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan (D.-G.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22533"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20530"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(19990915)40:4<497::AID-NEU7>3.0.CO;2-#"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052704499"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(99)70285-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.312.7039.1132"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s002210050313","article-title":"Modulation of mRNA expression of the neurotrophins of the nerve growth factor family and their receptors in the septum and hippocampus of rats after transient postnatal thyroxine treatment. 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