{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:09:35Z","timestamp":1785499775238,"version":"3.56.0"},"reference-count":34,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"published-print":{"date-parts":[[2009]]},"abstract":"Evidence suggests that the activation of the transcription factor hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) may promote cell survival in hypoxic or ischemic brain. To help understand the role of HIF-1\u03b1 in neonatal hypoxic-ischemic brain injury, mice with conditional neuron-specific inactivation of HIF-1\u03b1 underwent hypoxia-ischemia (HI). Mice heterozygous for Cre recombinase under the control of the calcium\/calmodulin-dependent kinase II promoter were bred with homozygous \u2018floxed\u2019 HIF-1\u03b1 transgenic mice. The resulting litters produced mice with a forebrain predominant neuronal deletion of HIF-1\u03b1 (HIF-1\u03b1<sup>\u0394<\/sup><sup>\/<\/sup><sup>\u0394<\/sup>), as well as littermates without the deletion. In order to verify reduction of HIF-1\u03b1 at postnatal day 7, HIF-1\u03b1<sup>\u0394<\/sup><sup>\/<\/sup><sup>\u0394<\/sup> and wild-type mice were exposed to a hypoxic stimulus (8% oxygen) or room air for 1 h, followed by immediate collection of brain cortices for determination of HIF-1\u03b1 expression. Results of Western blotting of mouse cortices exposed to hypoxia stimulus or room air confirmed that HIF-1\u03b1<sup>\u0394<\/sup><sup>\/<\/sup><sup>\u0394<\/sup> cortex expressed a minimal amount of HIF-1\u03b1 protein compared to wild-type cortex with the same hypoxic stimulus. Subsequently, pups underwent the Vannucci procedure of HI at postnatal day 7: unilateral ligation of the right common carotid artery followed by 30 min of hypoxia (8% oxygen). Immunofluorescent staining of brains 24 h after HI confirmed a relative lack of HIF-1\u03b1 in the HIF-1\u03b1<sup>\u0394<\/sup><sup>\/<\/sup><sup>\u0394<\/sup> cortex compared to the wild type, and that HIF-1\u03b1 in the wild type is located in neurons. HIF-1\u03b1 expression was determined in mouse cortex 24 h after HI. Histological analysis for the degree of injury was performed 5 days after HI. HIF-1\u03b1 protein expression 24 h after HI showed a large increase of HIF-1\u03b1 in the hypoxic-ischemic cortex of the wild-type compared to the hypoxic only cortex. Histological analysis revealed that HI injury was increased in the neuronally deficient HIF-1\u03b1<sup>\u0394<\/sup><sup>\/<\/sup><sup>\u0394<\/sup> mouse brain (p < 0.05) and was more severe in the cortex. Genetic reduction of neuronal HIF-1\u03b1 results in a worsening of injury after neonatal HI, with a region-specific role for HIF-1\u03b1 in the setting of neonatal brain injury.<\/jats:p>","DOI":"10.1159\/000232563","type":"journal-article","created":{"date-parts":[[2009,8,12]],"date-time":"2009-08-12T13:53:17Z","timestamp":1250085197000},"page":"452-458","source":"Crossref","is-referenced-by-count":53,"title":["HIF-1\u03b1-Deficient Mice Have Increased Brain Injury after Neonatal Hypoxia-Ischemia"],"prefix":"10.1159","volume":"31","author":[{"given":"R. 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