HIF1α Signaling in the Endogenous Protective Responses after Neonatal Brain Hypoxia-Ischemia.
Brain
Development
Hypoxia-inducible factor 1α
Hypoxia/ischemia
Journal
Developmental neuroscience
ISSN: 1421-9859
Titre abrégé: Dev Neurosci
Pays: Switzerland
ID NLM: 7809375
Informations de publication
Date de publication:
05 Mar 2019
05 Mar 2019
Historique:
received:
28
09
2018
accepted:
27
11
2018
pubmed:
6
3
2019
medline:
6
3
2019
entrez:
6
3
2019
Statut:
aheadofprint
Résumé
Hypoxia-inducible factor 1α (HIF1α) is a key regulator of oxygen homeostasis, and its target genes mediate adaptive, protective, and pathological processes. The role of HIF1α in neuronal survival is controversial and the brain maturation stage is important in determining its function in brain ischemia or hypoxia-ischemia (HI). In this study, we used neuron-specific HIF1α knockout mice at postnatal day 9 (P9), and immature cortical neurons (days 7-8 in vitro) treated with the HIF1α inhibitor 2-methoxyestradiol (2ME2) or stabilizer dimethyloxalylglycine (DMOG), to examine the function of neuronal HIF1α in neonatal HI in vivo (Vannucci model) and in vitro (oxygen glucose deprivation, OGD). Inhibition of HIF1α with 2ME2 in primary neurons or deletion of neuronal HIF1α in P9 mice increased both necrotic and apoptotic cell death following HI, as evaluated by the protein levels of 145/150-kDa and 120-kDa spectrin breakdown products 24 h after HI. DMOG attenuated neuronal death right after OGD. Acute pharmacological manipulation of HIF1α synchronously regulated the expression of its targets, vascular endothelial growth factor (VEGF) and erythropoietin (Epo), in the same manner. The in vivo findings agree with our previous data using the same HIF1α-deficient mice at an earlier age. This study confirms the role of neuronal HIF1α signaling in the endogenous protective responses following HI in the developing brain.
Identifiants
pubmed: 30836371
pii: 000495879
doi: 10.1159/000495879
pmc: PMC6728223
mid: NIHMS1045701
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1-10Subventions
Organisme : NINDS NIH HHS
ID : R01 NS084057
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097299
Pays : United States
Informations de copyright
© 2019 S. Karger AG, Basel.
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