Hypoxic preconditioning protection is eliminated in HIF-1α knockout mice subjected to neonatal hypoxia-ischemia.

ABSTRACT:

Background

Hypoxic preconditioning (HPc) protects the neonatal brain in the setting of hypoxia-ischemia (HI). The mechanisms of protection may depend on activation of hypoxia-inducible factor (HIF-1α). This study sought to clarify the role of HIF-1α after HPc and HI.

Methods

To induce HPc, HIF-1α knockout and wild-type (WT) mice were exposed to hypoxia at postnatal day 6. At day 7, the mice underwent HI. Brain injury was determined by histology. HIF-1α, downstream targets, and markers of cell death were measured by western blot.

Results

HPc protected the WT brain compared with WT without HPc, but did not protect the HIF-1α knockout brain. In WT, HIF-1α increased after hypoxia and after HI, but not with HPc. The HIF-1α knockout showed no change in HIF-1α after hypoxia,

SUBMITTER: Sheldon RA 

PROVIDER: S-EPMC4167022 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature