{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T17:53:15Z","timestamp":1774288395100,"version":"3.50.1"},"reference-count":36,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"abstract":"<jats:p>Introduction: Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) has a wide-ranging role in the cellular responses to hypoxia. We previously found that neuron-specific HIF-1\u03b1-deficient mice (HIF-KO) that underwent neonatal hypoxia-ischemia (HI) had increased brain injury suggesting its neuroprotective function. To investigate whether HIF-1\u03b1 is also involved in the mechanisms of protection by hypothermia (HT), the standard of care for hypoxic-ischemic encephalopathy, we tested the effect of HT on HIF-KO and wild-type (WT) littermates after HI in postnatal day 9 mice. Methods: Cooling at 32\u00b0C began 1 h following HI and lasted for 3.5 h. Mice were perfused 5\u20137 days later for histological determination of injury severity. For Western blots, mice were killed 4 h or 24 h after HI with HT or HI with normothermia (NT) and ipsilateral cortices and hippocampi were evaluated for expression of HIF-1\u03b1, spectrin, ERK1\/2, phosphorylated-ERK1\/2 (p-ERK), and RNA-binding motif protein 3 (RBM3), one of the main cold-inducible mRNA-binding proteins. Results: Histological evaluation showed WT mice with HT had less injury than WT with NT, but HIF-KO mice showed no reduction of injury with HT. Regionally, the reduction of injury in WT with HT is greater in the hippocampus than in the cortex. Protein expression of HIF-1\u03b1 was lower in HIF-KO cortex at 4 h with NT or HT and at 24 h with NT, but HIF-1\u03b1 was higher in WT with NT at 24 h. Expression of spectrin 145\/150 in WT cortex with HT was not different than sham at 4 h, indicating limitation of necrosis with HT. In the HIF-KO cortex at 4 h spectrin 145\/150 was higher in both NT and HT, indicating no protection with HT. In the hippocampus at 4 h and 24 h, spectrin 145\/150 was elevated in all groups compared to sham. ERK activity, as represented by the ratio of p-ERK\/ERK, was upregulated at 24 h in the cortex in WT with NT or HT compared to sham and in HIF-KO mice with NT or HT treatment compared to sham. RBM3 was elevated at 4 h in both WT and HIF-KO cortex with HT, but there was no change in the hippocampus. Conclusion: These results support a critical role for HIF-1\u03b1 in the mechanisms of protection with HT.<\/jats:p>","DOI":"10.1159\/000544949","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T13:05:41Z","timestamp":1743253541000},"page":"105-114","source":"Crossref","is-referenced-by-count":0,"title":["Hypothermia treatment in Hypoxia-Inducible Factor-1\u03b1 Knockout Mice with Hypoxia-Ischemia"],"prefix":"10.1159","volume":"48","author":[{"given":"R. Ann","family":"Sheldon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangning","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuxin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas R.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0560-9045","authenticated-orcid":false,"given":"Donna M.","family":"Ferriero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.021"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2009.09.006"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.12"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1159\/000232563"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.53"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199602000-00003"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2012.15"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1159\/000495880"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.47.1.32"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1159\/000523990"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1159\/000495879"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2024.04.014"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2021.101257"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2243-10.2011"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(00)01181-9"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5474"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01838.x"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3174"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0449-07.2007"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410090206"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-15-05775.2000"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02324.x"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1113\/JP275649"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/s0306-4522(00)00169-x"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.09.052"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25158204"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020706"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181c13326"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01026"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci14040341"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-1706-y"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-021-10213-y"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24943"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.587815"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.08.019"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.03.012"}],"container-title":["Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/dne\/article-pdf\/doi\/10.1159\/000544949\/4358147\/000544949.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000544949","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T17:01:25Z","timestamp":1774285285000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000544949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,29]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,3,23]]},"published-print":{"date-parts":[[2026,3,24]]}},"URL":"https:\/\/doi.org\/10.1159\/000544949","archive":["Portico"],"relation":{},"ISSN":["0378-5866","1421-9859"],"issn-type":[{"value":"0378-5866","type":"print"},{"value":"1421-9859","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,29]]}}}