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Hypoxic\u2013ischemic brain injury was induced in 7\u2010day\u2010old rats. Pups were treated with either doxycycline (HI+doxy) or saline (HI+vehicle) by intraperitoneal injection at 1\u2003h after hypoxia\u2013ischemia (HI). At 6\u2003h after HI, MnCl<jats:sub>2<\/jats:sub> was injected intraperitoneally for later manganese\u2010enhanced magnetic resonance imaging (MRI). MRI was performed with diffusion\u2010weighted imaging on day 1 and T<jats:sub>1<\/jats:sub>\u2010weighted imaging and diffusion tensor imaging at 7, 21 and 42\u2003days after HI. Animals were killed after MRI on day 42 and histological examinations of the brains were performed. There was a tendency towards lower lesion volumes on diffusion maps among HI+doxy than HI+vehicle rats at 1\u2003day after HI. Volumetric MRI showed increasing differences between groups with time after HI, with less cyst formation and less cerebral tissue loss among HI+doxy than HI+vehicle pups. HI+doxy pups had less manganese enhancement on day 7 after HI, indicating reduced inflammation. HI+doxy pups had higher fractional anisotropy on diffusion tensor imaging in major white matter tracts in the injured hemisphere than HI+vehicle pups, indicating less injury to white matter and better myelination. Histological examinations supported the MRI results. Lesion size on early MRI was highly correlated with final injury measures. In conclusion, a single dose of doxycycline reduced long\u2010term cerebral tissue loss and white matter injury after neonatal HI, with an increasing effect of treatment with time after injury.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2012.08114.x","type":"journal-article","created":{"date-parts":[[2012,5,18]],"date-time":"2012-05-18T01:15:49Z","timestamp":1337303749000},"page":"2006-2016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Doxycycline treatment in a neonatal rat model of hypoxia\u2013ischemia reduces cerebral tissue and white matter injury: a longitudinal magnetic resonance imaging study"],"prefix":"10.1111","volume":"36","author":[{"given":"Marius","family":"Wider\u00f8e","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne B","family":"Havnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tora Sund","family":"Morken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Skranes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e5l\u2010Erik","family":"Goa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2010Mari","family":"Brubakk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10242"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10609"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21607"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21890"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.09.023"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2008.02.005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.7.1411"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04918.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041996"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600121"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(01)00487-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000046140"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2009.07.013"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.090061"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600025"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2006.06.010"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.108837"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21380"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22869"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(94)00177-2"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.08.012"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200104000-00012"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209532200"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410090206"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.07.051"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1267"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.01.028"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01064"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000085978"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70294-1"},{"key":"e_1_2_8_32_1","first-page":"51","article-title":"Hypoxic\u2010ischemic brain injury in the neonatal rat model: relationship between lesion size at early MR imaging and irreversible infarction","volume":"27","author":"Wang Y.","year":"2006","journal-title":"AJNR Am. 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